bromochloroacetic-acid and Uterine-Cervical-Neoplasms
bromochloroacetic-acid has been researched along with Uterine-Cervical-Neoplasms* in 211 studies
Reviews
13 review(s) available for bromochloroacetic-acid and Uterine-Cervical-Neoplasms
Article | Year |
---|---|
Adenoid basal carcinoma combined with invasive squamous cell carcinoma of uterine cervix: A case report of a 37-year-old woman and literature review.
Adenoid basal carcinoma (ABC) is uncommon malignancy of the uterine cervix and it can be pure or combined with cervical intraepithelial lesions. There were less than 20 cases of ABC combined with invasive squamous carcinoma (mixed type) in English literature. These cases had similar properties as seen at postmenopausal women and diagnosed with abnormal cervical smear findings. Here we present a case of 37-year-old woman who suffered from spotting and received endocervical curettage. The pathological report revealed squamous cell carcinoma (SCC) of the cervix. The patient underwent type 3 radical hysterectomy and bilateral pelvic and para-aortic lymph node dissection. The final pathological report revealed SCC coexisting with ABC. Human papillomavirus (HPV) 16,18 and others (11 types) were negative in both components of the mixed tumor by in situ hybridization detection. Our case was cytokeratin 7 negative, cytokeratin 8 positive and p63 positive which supports the hypothesis that mixed type cervical carcinoma originates from endocervical reserve cells. Topics: Adenocarcinoma; Adult; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lymph Nodes; Neoplasm Invasiveness; Uterine Cervical Neoplasms | 2019 |
[Molecular markers of carcinogenesis in the diagnostics of cervical cancer].
Cervical carcinoma is the most frequent disease of the reproductive organ and is the second most common cancer in women after breast cancer. As it is characterized by high mortality, new diagnostic methods are needed, for example tumor markers, enabling earlier diagnosis and rapid detection of recurrence after therapy. Different tumor markers may be useful in the diagnostics of cervical cancer, for example squamous cell carcinoma antigen (SCC-Ag), tissue polypeptide antigen (TPA), and CYFRA 21-1, as well as some cytokines such as vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor, and macrophage colony-stimulating factor (M-CSF). About 150 genes connected with the carcinogenesis of cervical carcinoma have been identified. This paper is devoted to evaluating the diagnostic usefulness of molecular markers of carcinogenesis, especially P53, Bcl-2, Brn-3a, and MCM, and comparing the results with those of typical tumor markers or cytokines useful in diagnosing this type of cancer. It was shown that telomerase and Brn-3a proteins demonstrate usefulness in screening examination, P53 in monitoring the effectiveness of therapy, and Bcl-2 as a survival prognostic factor. In summary, it is evident that molecular makers of carcinogenesis are helpful in the diagnostics of cervical cancer, but further investigation and confirmation by a prospective study is necessary. Topics: Adaptor Proteins, Signal Transducing; Antigens, Neoplasm; Biomarkers, Tumor; Carrier Proteins; Female; Genes, bcl-2; Humans; Keratin-19; Keratins; Macrophage Colony-Stimulating Factor; Nuclear Proteins; Serpins; Tissue Polypeptide Antigen; Transcription Factor Brn-3A; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms; Vascular Endothelial Growth Factor A | 2009 |
The serum assay of tumour markers in the prognostic evaluation, treatment monitoring and follow-up of patients with cervical cancer: a review of the literature.
Pre-treatment serum squamous cell carcinoma antigen [SCC] levels are elevated in 28-88% of patients with squamous cell cervical cancer, and are related to tumour stage, tumour size, depth of stromal invasion, lymph-vascular space status, parametrial involvement and lymph node status. The clinical relevance of pre-treatment serum SCC assay is still debated. Some authors reported that it has no prognostic value, some others found that it is related to survival at univariate analysis, and some others detected that is an independent prognostic variable for survival. Serial SCC measurements reflect both the tumour response to treatment and the clinical outcome of patients. Increasing SCC levels can precede the clinical diagnosis of recurrent disease in 46-92% of the cases, with a mean lead time ranging from 2 to 8 months. According to some authors serum SCC assay during the follow-up does not improve the cure rate of patients who will ultimately develop a recurrence. However, it has been recently reported that the performance of a positron emission tomography [PET] in patients with asymptomatic SCC elevation can sometimes allow an earlier diagnosis of relapse with a survival benefit. SCC is a more sensitive serum tumour marker than CYFRA 21-1 for squamous cell cervical cancer in most series. Pre-treatment CA 125 levels are raised in 20-75% of patients with cervical adenocarcinoma, and reflect tumour stage, tumour size, histological grade, cervical stromal invasion, lymph-vascular space status and lymph node status. Elevated serum CA 125 has been also detected in patients with squamous cell cervical cancer, but with a positivity rate lower than that found in patients with cervical adenocarcinoma. Pre-treatment CA 125 levels appear to have a prognostic value, and rising serum CA 125 during follow-up may precede or be coincident with the clinical diagnosis of recurrent cervical adenocarcinoma. Serum levels of vascular endothelial growth factor [VEGF] are often elevated in patients with cervical cancer, and decrease significantly after successful treatment. However, the clinical relevance of serum VEGF assay is still investigational. Topics: Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Keratin-19; Keratins; Neoplasm Proteins; Prognosis; Serpins; Uterine Cervical Neoplasms; Vascular Endothelial Growth Factor A | 2008 |
Molecular markers of miscellaneous primary and metastatic tumors of the uterine cervix.
Miscellaneous primary tumors of the uterine cervix are rare. Markers which can be utilized to detect these tumors are very few and in most cases, have not been clinically validated. The information provided in this article will help in developing strategies to discover novel markers and initiate translational research in this ignored area. Based on the reported studies, cytokeratin markers are common in many tumors and few of these rare cancers demonstrate human papilloma-virus (HPV) and Epstein Bar virus (EBV) infection. Due to the very low prevalence of these tumors, epidemiological studies have not been conducted and the etiology of these tumors is largely unknown. Topics: Biomarkers, Tumor; Carcinoma; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Keratins; Lipoma; Melanoma; Neurilemmoma; Rare Diseases; Sarcoma; Uterine Cervical Neoplasms | 2007 |
[Tumor makrers in cervical cancer].
IMeasurement of tumor markers level in human body fluids, mainly in serum may be useful for diagnosis, therapy monitoring and early recurrence detection. SCC-Ag, Cyfra 21-1, CEA, CA 125 and TPS are of a clinical value in uterine cervical cancer despite their diverse significance. Other biological markers that could be measured in serum as well as in tumor tissue are cytokines: VEGF, IL-6, IL-8, IL-4, IL-10, leptin, stromal drive factor (SDF- 1), although assessment of their importance needs further examination. Elevation of uterine cervical cancer hypoxia markers such as HIF 1a, CA 9, GLUT-1 is combined with poorer clinical outcome prognosis. Topics: Antigens, Neoplasm; Biomarkers, Tumor; Blood Chemical Analysis; CA-125 Antigen; Carcinoembryonic Antigen; Female; Humans; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-8; Keratin-19; Keratins; Neoplasm Staging; Prognosis; Serpins; Uterine Cervical Neoplasms; Vascular Endothelial Growth Factor A | 2007 |
[Tumor markers in uterine cancers].
In diagnosing uterine cancers, cells and tissue samples can be directly obtained from the lesion. Cytologic and histologic investigation is the best method for screening and early detection of primary uterine cancers. Tumor markers may be useful for monitoring the clinical course of therapy and early detection of recurrence for which cytologic examination can not be done. Moreover, high levels of tumor markers may represent tumor invasiveness and metastasis to lymph nodes and/or other organs, and may indicate a poor prognosis for the patient. Strictly speaking, tumor markers are not tumor-specific but tumor-associated substances. They can be elevated in sera from healthy individuals under various conditions, and from patients with benign tumors. Squamous cell carcinoma-associated antigen (SCC) is relatively tumor-specific, and widely used for monitoring patients with squamous cell carcinoma not only of the uterine cervix. On the other hand, there is no specific tumor marker for uterine corpus carcinoma. Combination assay of several tumor markers including cancer antigen 125 (CA125) as a core marker may be of greater diagnostic value in cases of uterine corpus carcinoma. Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Neoplasm Proteins; Serpins; Tissue Polypeptide Antigen; Uterine Cervical Neoplasms; Uterine Neoplasms | 2002 |
[Diagnosis and clinical significance of disseminated tumor cells in bone marrow].
Topics: Bone Marrow; Bone Marrow Examination; Bone Marrow Neoplasms; Breast Neoplasms; Colorectal Neoplasms; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymphatic Metastasis; Neoplastic Cells, Circulating; Ovarian Neoplasms; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Stomach Neoplasms; Uterine Cervical Neoplasms | 2000 |
Primary malignant melanoma of the uterine cervix: case report with world literature review.
A 63-year-old patient with a malignant melanoma of the uterine cervix is described. Subtle epitheliotropism of the neoplastic cells within the endocervical columnar epithelium suggested melanoma in situ and the possibility of a primary uterine cervical melanoma, despite a negative anti-S-100 protein immunohistochemical stain. An exhaustive clinical workup, and ultimately, complete autopsy failed to reveal any other primary tumor site, and the diagnosis of melanoma was confirmed by histology and immunohistochemistry on the hysterectomy specimen. A world literature review revealed 54 previously reported cases of uterine cervical melanoma of which 43 had been reported as primary uterine cervical melanoma. A true intraepithelial melanocytic component was found in only 14 of those cases, however, and none of those reports illustrated this with the clarity with which it was seen in the endocervical glandular and surface columnar epithelium of the present case. Primary uterine cervical melanoma is usually discovered at an advanced stage and is no longer amenable to curative therapy. Even when this tumor is discovered early, however, the diagnosis may be unnecessarily delayed if the often subtle interaction of the neoplastic cells with the benign cervical squamous or glandular epithelium is not appreciated, or if the possibility of malignant melanoma is not entertained based on other histologic or immunohistologic characteristics of the tumor cells. Topics: Actins; Desmin; Epithelium; Fatal Outcome; Female; Humans; Hysterectomy; Immunohistochemistry; Keratins; Melanocytes; Melanoma; Melanoma, Amelanotic; Middle Aged; Mucin-1; Neoplasm Metastasis; Neoplasm Recurrence, Local; S100 Proteins; Uterine Cervical Neoplasms; Uterine Hemorrhage | 1999 |
Adenoid basal carcinoma of the uterine cervix: immunohistochemical study and literature review.
Adenoid basal carcinoma of the uterine cervix is rare and its cell origin is still obscure. We report a case of adenoid basal carcinoma of the uterine cervix discovered incidentally in a 69-year-old woman who had been hysterectomized due to endometrial adenocarcinoma of the uterine corpus. Histologically, small round-to-oval cancer cell nests with peripheral cell palisading were seen budding from the basal cell layer of the uterine cervix showing carcinoma in situ. Immunohistochemically, the basaloid cells of the adenoid basal carcinoma were positive for keratins 14, 17 and 19 and resembled reserve cells of the cervical epithelium. The results of this study clearly demonstrated that adenoid basal carcinoma shows a phenotype similar to reserve cells of the uterine cervix. A review of the literature indicated that this tumor has a favorable prognosis and should be clearly separated from adenoid cystic carcinoma, which has a much poorer outcome. Topics: Aged; Biomarkers, Tumor; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Carcinoma, Endometrioid; Female; Humans; Immunohistochemistry; Keratins; Neoplasms, Multiple Primary; Proliferating Cell Nuclear Antigen; Receptors, Estrogen; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms; Uterine Neoplasms | 1997 |
The problem of replacement and differentiation of the intestinal epithelium: its relation to squamous metaplasia in the uterine cervix.
Topics: Animals; Carcinoma, Squamous Cell; Cell Differentiation; Cervix Uteri; Female; Intestinal Mucosa; Keratins; Metaplasia; Phenotype; Precancerous Conditions; Rats; Rats, Wistar; Urodela; Uterine Cervical Neoplasms | 1997 |
The dynamics of keratin expression in malignant transformation of cervical epithelium: a review.
To review basic and clinical aspects of cytoskeletal keratin expression in normal cervical epithelia as well as in preneoplastic and malignant epithelia of the uterine cervix.. The results of extensive studies from our group and other groups on keratin phenotyping in normal premalignant and malignant cervical epithelia were summarized.. All studies involving keratin expression in the cervix were reviewed, as were general studies on keratin expression in which the cervix was mentioned and studies relevant to understanding cervical cancer etiology (36 studies).. From these studies, keratin phenotypes of the various epithelia were derived. The phenotypes were correlated to existing theories on the development of cervical carcinoma.. It is possible to distinguish the various epithelial types in the normal cervix based on their keratin expression patterns. Reserve cells display a bidirectional keratin pattern, comprising keratins typical of both squamous and simple types of differentiation, reflecting the bipotential nature of these cells. Cervical intraepithelial neoplasia can be divided into two subpopulations, one characterized by the reserve cell keratin phenotype and the other by a keratin phenotype typical of nonkeratinizing squamous epithelia. The first population also contains the simple keratins, the relative percentage of which increases with increasing degree of dysplasia. We therefore suggest that these lesions are progressive in nature. Carcinomas show a differentiation-related keratin expression pattern in addition to the basic reserve cell keratin phenotype. Adenocarcinomas also have been shown to express most of the reserve cell keratins. The latter observation indicates a common progenitor for both carcinoma types. Topics: Carcinoma in Situ; Cervix Uteri; Epithelium; Female; Forecasting; Humans; Keratins; Metaplasia; Precancerous Conditions; Research; Uterine Cervical Neoplasms | 1993 |
Alveolar soft part sarcoma of the uterine cervix.
We describe two cases of alveolar soft part sarcoma (ASPS) that occurred as a primary lesion in the uterine cervix. In both cases, the tumor exhibited the typical histologic features of ASPS. In one case, the material for immunohistochemical staining and electron microscopy was available, and the findings of these studies were consistent with the diagnosis of ASPS. A review of the literature disclosed seven previous cases of ASPS occurring in the female genital tract. The tumor was located in the uterine cervix in only three cases. Although ASPS most commonly involves the soft tissues of the extremities and the head and neck region, it can also occur in rather unusual locations such as the female genital tract. Pathologists should be aware of these unexpected occurrences. Topics: Actins; Adult; Desmin; Female; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; S100 Proteins; Sarcoma; Uterine Cervical Neoplasms; Vimentin | 1989 |
Expression of cytokeratins in early neoplastic epithelial lesions of the uterine cervix.
Polyclonal and monoclonal antibodies to cytokeratin polypeptides were used to study the expression of these intermediate filament proteins in normal, squamous metaplastic, and neoplastic epithelium of the uterine cervix, in order to investigate the morphogenesis of early epithelial changes preceding cervical squamous cell carcinoma. A polyclonal keratin antiserum showed a positive reaction in all different epithelial cell types of the uterine cervix. A positive reaction was also found in subcolumnar reserve cell hyperplasia, in squamous metaplastic and dysplastic cells, and in (squamous) carcinoma in situ. A monoclonal antibody specific for columnar epithelium (RGE 53) gave a positive reaction in endocervical columnar cells and in some immature metaplastic cells but was negative in subcolumnar reserve cells, squamous (metaplastic) cells, dysplastic cells, and most cases of carcinoma in situ. Another monoclonal cytokeratin antibody (RKSE 60) pointed to early keratinization in light microscopically nonkeratinizing squamous (metaplastic) and dysplastic epithelium. A possible overlap in staining patterns of RGE 53 and RKSE 60 was seen in some cases of immature metaplasia. Morphologic changes occurring in the transformation zone upon dedifferentiation are accompanied by alterations in cytokeratin expression. Similarities in cytokeratin expression were found between dysplasia and carcinoma in situ on one hand and subcolumnar reserve cell hyperplasia and squamous metaplasia on the other. This study favors an epithelial origin and a squamoid nature of subcolumnar reserve cells. Topics: Adult; Antibodies, Monoclonal; Carcinoma in Situ; Cervix Uteri; Female; Humans; Hyperplasia; Keratins; Metaplasia; Middle Aged; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1985 |
Trials
1 trial(s) available for bromochloroacetic-acid and Uterine-Cervical-Neoplasms
Article | Year |
---|---|
Tamoxifen modulates the expression of Ki67, apoptosis, and microvessel density in cervical cancer.
The aim of the study was to investigate if a short-term administration of high-dose Tamoxifen (Tam) could affect the expression of biologically relevant biochemical parameters in cervical cancer tissue.. The study was conducted in 24 patients with histologically confirmed cervical tumors. Biopsies were obtained by colposcopy on day 0 in all patients, who then received either 80 mg/die or 160 mg/die for 5 consecutive days until the second biopsy was obtained. Immunohistochemistry was performed with antiestrogen receptor (ER), anti-Ki67, anticaspase cleavage product of keratin 18 (M30), and anti-CD31 monoclonal antibodies.. Eleven (45.8%) of 24 cervical tumors were ER positive. The percentage of Ki67-positive tumor cells in pre-Tam biopsies was significantly higher than the percentage in the corresponding posttreatment biopsies (z = 4.29, P = 0.0001). No difference in the pretreatment percentage of Ki67-positive cells according to ER status was found. The percentage of M30 positivity was higher in post-Tam than in pre-Tam biopsies. Microvessel density values in pre-Tam biopsies were significantly higher than corresponding values in posttreatment tissues (z = -3.72, P = 0.0002). The reduction in the percentage of Ki67-positive tumors was significantly (z = 3.58, P = 0.0003) higher in ER-positive than in ER-negative tumors, whereas no difference in Tam-induced reduction of microvessel density values according to ER status (z = -0.18, P = 0.85) was found. Tam treatment did not induce any change of M30 positivity in ER-positive tumors, whereas in ER-negative tumors, it produced a significant (P = 0.015) increase in the percentage of M30-positive cells in post-Tam versus pre-Tam biopsies.. A short-term treatment with Tam at doses 4-8-fold higher than those in conventional schemes is associated with modifications of biological parameters associated with tumor cell proliferation, apoptosis, and neoangiogenesis in cervical cancer. Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Apoptosis; Blood Vessels; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Middle Aged; Platelet Endothelial Cell Adhesion Molecule-1; Receptors, Estrogen; Tamoxifen; Uterine Cervical Neoplasms | 2001 |
Other Studies
197 other study(ies) available for bromochloroacetic-acid and Uterine-Cervical-Neoplasms
Article | Year |
---|---|
Value of routine cytokeratin immunohistochemistry in detecting low volume disease in cervical cancer.
In cervical cancer, sentinel lymph nodes (SLNs) are processed according to the pathological ultrastaging protocol. According to current guidelines, immunohistochemistry with pancytokeratin antibodies is performed in addition to step sectioning with hematoxylin and eosin (H&E), aiding the detection of low volume disease (micrometastasis and isolated tumor cells (ITC)). We studied the added clinical value, and costs, of routine immunohistochemistry (IHC).. We retrospectively included all FIGO stage IA-IIA1 cervical cancer patients who had undergone SLN procedures at UMC Utrecht from 2008 to 2020. Pathological data were derived from the Dutch Pathology Registry (PALGA) including SLN tumor status and number of slides stained with IHC.. In total 234 cervical cancer patients were included. In the 516 surgically resected SLN specimens, 630 SLNs were discovered by the pathologist. Hereof, 579 SLNs from 211 patients were routinely processed with IHC. IHC identified three patients with micrometastasis and five patients with ITC undetected with H&E staining. Thereby, IHC significantly increased the number of patients with low volume disease from 11 (5.3%) to 19 patients (9.1%) (p = 0.04). To achieve this, 3791 slides were stained with IHC at an estimated additional cost of €94,775. In 1.4% (95% CI 0.3%-4.3%) of patients routine use of IHC adjusted the adjuvant treatment.. Routine use of IHC increases detection of low volume disease in cervical cancer SLNs compared to step sectioning with H&E alone by nearly 4%, with an impact on therapeutic strategy-decisions in about 1% of patients. In view of the high associated costs, cost-effectiveness of routine IHC is questionable. Topics: Female; Humans; Immunohistochemistry; Keratins; Neoplasm Micrometastasis; Retrospective Studies; Uterine Cervical Neoplasms | 2022 |
Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia.
The transition zones of the squamous and columnar epithelia constitute hotspots for the emergence of cancer, often preceded by metaplasia, in which one epithelial type is replaced by another. It remains unclear how the epithelial spatial organization is maintained and how the transition zone niche is remodelled during metaplasia. Here we used single-cell RNA sequencing to characterize epithelial subpopulations and the underlying stromal compartment of endo- and ectocervix, encompassing the transition zone. Mouse lineage tracing, organoid culture and single-molecule RNA in situ hybridizations revealed that the two epithelia derive from separate cervix-resident lineage-specific stem cell populations regulated by opposing Wnt signals from the stroma. Using a mouse model of cervical metaplasia, we further show that the endocervical stroma undergoes remodelling and increases expression of the Wnt inhibitor Dickkopf-2 (DKK2), promoting the outgrowth of ectocervical stem cells. Our data indicate that homeostasis at the transition zone results from divergent stromal signals, driving the differential proliferation of resident epithelial lineages. Topics: Adenocarcinoma; Animals; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Cell Lineage; Cellular Microenvironment; Cervix Uteri; Epithelium; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Homeostasis; Humans; Keratins; Metaplasia; Mice, Inbred C57BL; Organoids; Receptors, Notch; Stem Cells; Stromal Cells; Transcription, Genetic; Uterine Cervical Neoplasms; Wnt Signaling Pathway | 2021 |
Squamous cell carcinoma with sarcomatoid differentiation or carcinosarcoma of the uterine cervix associated with HPV33 infection: report of a rare case.
Squamous cell carcinoma is the most common malignant tumor of the uterine cervix with a well-documented link to infection with human papillomaviruses (HPV). According to a recent classification, there are several morphological variants of cervical squamous carcinoma, without reference to sarcomatoid squamous cell carcinoma, which is well described in other organs.. In this paper, we describe an extremely rare case of a 77-year-old woman with primary malignant cervical tumor displaying biphasic histomorphology with an epithelioid and sarcomatoid part; the latter was immunohistochemistry positive for cytokeratin and vimentin. The association with a high-grade squamous intraepithelial lesion and molecular proof of HPV33 infection in the tumor tissue supported our diagnosis of carcinoma with partial sarcomatoid differentiation.. We report a rare case of a primary cervical epithelial tumor with a partial sarcomatoid phenotype, an unequivocal HPV infection, and an associated precancerous lesion in the cervical mucosa. This is the first description of an HPV33 infection underlying a biphasic epithelioid-sarcomatous tumor of the uterine cervix. The terminology overlap between sarcomatoid carcinoma and carcinosarcoma is also discussed. Topics: Aged; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Differentiation; Cervix Uteri; Female; Humans; Keratins; Papillomavirus Infections; Sarcoma; Uterine Cervical Neoplasms | 2020 |
Detection of circulating tumor cells in cervical cancer using a conditionally replicative adenovirus targeting telomerase-positive cells.
Circulating tumor cells (CTC) are newly discovered biomarkers of cancers. Although many systems detect CTC, a gold standard has not yet been established. We analyzed CTC in uterine cervical cancer patients using an advanced version of conditionally replicative adenovirus targeting telomerase-positive cells, which was enabled to infect coxsackievirus-adenovirus receptor-negative cells and to reduce false-positive signals in myeloid cells. Blood samples from cervical cancer patients were hemolyzed and infected with the virus and then labeled with fluorescent anti-CD45 and anti-pan cytokeratin antibodies. GFP (+)/CD45 (-) cells were isolated and subjected to whole-genome amplification followed by polymerase chain reaction analysis of human papillomavirus (HPV) DNA. CTC were detected in 6 of 23 patients with cervical cancers (26.0%). Expression of CTC did not correlate with the stage of cancer or other clinicopathological factors. In 5 of the 6 CTC-positive cases, the same subtype of HPV DNA as that of the corresponding primary lesion was detected, indicating that the CTC originated from HPV-infected cancer cells. These CTC were all negative for cytokeratins. The CTC detected by our system were genetically confirmed. CTC derived from uterine cervical cancers had lost epithelial characteristics, indicating that epithelial marker-dependent systems do not have the capacity to detect these cells in cervical cancer patients. Topics: Adenoviridae; Adenoviridae Infections; Cell Line, Tumor; Female; HeLa Cells; Humans; Keratins; Neoplastic Cells, Circulating; Telomerase; Uterine Cervical Neoplasms; Virus Replication | 2018 |
Integrated genomic and molecular characterization of cervical cancer.
Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers. Topics: Adenocarcinoma; APOBEC-1 Deaminase; B7-H1 Antigen; Carcinoma, Squamous Cell; Caspase 8; DNA-Binding Proteins; Female; Genomics; HLA-A Antigens; Human papillomavirus 16; Humans; Keratins; Mitogen-Activated Protein Kinase Kinases; Molecular Targeted Therapy; Mutation; Nuclear Proteins; Phosphatidylinositol 3-Kinases; Programmed Cell Death 1 Ligand 2 Protein; Protein Serine-Threonine Kinases; Proteomics; Proto-Oncogene Proteins p21(ras); PTEN Phosphohydrolase; Receptor, ErbB-3; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; RNA, Long Noncoding; Signal Transduction; Transcription Factors; Uterine Cervical Neoplasms; Virus Integration | 2017 |
Quantitative interactome analysis reveals a chemoresistant edgotype.
Chemoresistance is a common mode of therapy failure for many cancers. Tumours develop resistance to chemotherapeutics through a variety of mechanisms, with proteins serving pivotal roles. Changes in protein conformations and interactions affect the cellular response to environmental conditions contributing to the development of new phenotypes. The ability to understand how protein interaction networks adapt to yield new function or alter phenotype is limited by the inability to determine structural and protein interaction changes on a proteomic scale. Here, chemical crosslinking and mass spectrometry were employed to quantify changes in protein structures and interactions in multidrug-resistant human carcinoma cells. Quantitative analysis of the largest crosslinking-derived, protein interaction network comprising 1,391 crosslinked peptides allows for 'edgotype' analysis in a cell model of chemoresistance. We detect consistent changes to protein interactions and structures, including those involving cytokeratins, topoisomerase-2-alpha, and post-translationally modified histones, which correlate with a chemoresistant phenotype. Topics: Antigens, Neoplasm; Blotting, Western; Carcinoma; Chromatography, Liquid; DNA Repair; DNA Topoisomerases, Type II; DNA-Binding Proteins; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; HeLa Cells; Histone Code; Histones; Humans; Immunoprecipitation; Keratins; Mass Spectrometry; Microscopy, Fluorescence; Phenotype; Protein Interaction Maps; Uterine Cervical Neoplasms | 2015 |
HeLa cell line xenograft tumor as a suitable cervical cancer model: growth kinetic characterization and immunohistochemistry array.
Cervical cancer is the seventh most common malignancy in both genders combined and the third most common cancer in women. Despite significant progress in treatments, cervical cancer is not completely curable. Therefore, further research is necessary in this area. Animal models are one of the most practical tools in the field of cancer research. The present study aimed to characterize the growth behavior and surface markers of HeLa cells after heterotopic and systemic inoculation to athymic nude mice.. Ten 6-week old female athymic C57BL/6 nude mice were used in this study. HeLa cells were inoculated into the flank or tail vein. The tumor volume was calculated and growth curves were drawn. Tumor-bearing mice were sacrificed and the lesions obtained after harvesting were analyzed in a pathology lab. Subsequently, one slide per tumor was stained with hematoxylin and eosin (H&E) and other slides were stained immunohistochemically by cytokeratins (CK), vimentin, P53, CD34, and Ki-67.. Tumor take rate, mean doubling time and latency period were 94.4%, 5.29 ± 3.57 days and 15.27 days, respectively. H&E results revealed highly malignant hyperchromatin epithelial cells. Immunohistochemical examination of the heterotopic tumors indicated greater expression of CK and less expression of vimentin compared to the metastatic ones. Sixty percent of cells were P53-positive and more than 80% were Ki-67-positive. CD34 expression indicated the intensity of angiogenesis in tumor.. This study represents a comprehensive description of a HeLa xenograft model for in vivo investigations, enabling researchers to assess new treatments for cervical cancer. Topics: Animals; Antigens, CD34; Carcinoma; Disease Models, Animal; Female; HeLa Cells; Heterografts; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Lung Neoplasms; Mice; Mice, Inbred C57BL; Mice, Nude; Time Factors; Tumor Burden; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms; Vimentin | 2014 |
[Cervical carcinoid with high-grade intraepithelial neoplasia: report of a case].
Topics: Adult; Breast Neoplasms; Carcinoid Tumor; Carcinoma, Adenoid Cystic; Carcinoma, Lobular; Chromogranin A; Diagnosis, Differential; Female; Humans; Hysterectomy; Keratins; Neoplasms, Multiple Primary; Ovarian Neoplasms; Sex Cord-Gonadal Stromal Tumors; Synaptophysin; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 2013 |
Loss of protein expression and recurrent DNA hypermethylation of the GNG7 gene in squamous cell carcinoma of the head and neck.
Although down-regulation of GNG7 in cancer was reported before, its role in carcinogenesis is poorly understood. It belongs to a family of large G-proteins that may be involved in cell-contact-induced growth arrest and function in tumor suppression. In the present study, we stained immunohistochemically 188 tumors derived from larynx or floor of the mouth for GNG7 protein and confronted it with clinicopathologic data. Moreover, we performed bisulfite pyrosequencing to analyze GNG7 promoter methylation. We identified recurrent loss of GNG7 protein expression in 68/188 (36%) cases and promoter hypermethylation in (42/98; 43%) primary tumors, predominantly in young patients (p < 0.001). Loss of GNG7 expression correlated with hypermethylation of GNG7 promoter region (p < 0.001). Moreover, loss of GNG7 protein expression correlated with tumor size (p = 0.012) and lack of cervical metastasis (p = 0.02) whereas sustained expression correlated with keratinization (p = 0.008). Taken together, loss of GNG7 protein expression is a frequent event in head and neck cancer. Moreover, our data suggest that hypermethylation of the promoter region of GNG7 is probably the mechanism of the observed inactivation. Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; DNA Methylation; DNA, Neoplasm; Female; Gene Expression Regulation, Neoplastic; GTP-Binding Protein gamma Subunits; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Promoter Regions, Genetic; Sequence Analysis, DNA; Tumor Burden; Uterine Cervical Neoplasms | 2012 |
Adenoid basal hyperplasia of the uterine cervix: a lesion of reserve cell type, distinct from adenoid basal carcinoma.
Adenoid basal hyperplasia is an underrecognized cervical lesion, resembling adenoid basal carcinoma, except the absence of deep invasion into the stroma. We report a series of 10 cases, all extending less than 1 mm from the basement membrane. Our results support the hypothesis that adenoid basal hyperplasia arises from reserve cells of the cervix. Lesions were found close to the squamocolumnar junction, in continuity with the nearby subcolumnar reserve cells. They shared the same morphology and immunoprofile using a panel of 4 antibodies (keratin 5/6, keratin 14, keratin 7 and p63) designed to differentiate reserve cells from mature squamous cells and endocervical columnar cells. We detected no human papillomavirus infection by in situ hybridization targeting high-risk human papillomavirus, which was concordant with the absence of immunohistochemical p16 expression. We demonstrated human papillomavirus infection in 4 (80%) of 5 adenoid basal carcinoma, which is in the same range as previous studies (88%). Thus, adenoid basal hyperplasia should be distinguished from adenoid basal carcinoma because they imply different risk of human papillomavirus infection and of subsequent association with high-grade invasive carcinoma. In our series, the most reliable morphological parameters to differentiate adenoid basal hyperplasia from adenoid basal carcinoma were the depth of the lesion and the size of the lesion nests. Furthermore, squamous differentiation was rare in adenoid basal hyperplasia and constant in adenoid basal carcinoma. Finally, any mitotic activity and/or an increase of Ki67 labeling index should raise the hypothesis of adenoid basal carcinoma. Topics: Adult; Aged; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Cervix Uteri; Epithelial Cells; Female; Humans; Hyperplasia; Keratins; Middle Aged; Uterine Cervical Neoplasms | 2012 |
The significance of hyperkeratosis in pap smears with squamous intraepithelial lesion.
It was the aim of this study to evaluate the significance of reporting hyperkeratosis in cervical smears.. Cervicovaginal smears with low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL), prepared from 2004 to 2007, were retrospectively reviewed. Anucleated squamous cells were counted. The smears were classified into two groups, based on the presence of <2 or ≥2 clusters of anucleated cells, and then compared.. Sixty Pap smears showing SILs (34 LSILs and 26 HSILs) as well as 120 random satisfactory smears without squamous or glandular abnormalities were selected. A statistically significant difference was found between the SIL group and the control group regarding the mean number of hyperkeratotic clusters (2.8 in the SIL and 1.9 in the control group; p = 0.012). Moreover, the mean number of hyperkeratotic clusters (3.3 in the LSIL and 2.2 in the HSIL group) had a statistically significant correlation with the diagnosis of the lesion as LSIL or HSIL (p = 0.0006).. Our findings suggest that hyperkeratosis in the form of ≥2 clusters of anucleated squamous cells could be an indicator of underlying LSIL. Topics: Adult; Female; Humans; Keratins; Papanicolaou Test; Retrospective Studies; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears | 2012 |
Leukocyte-mediated cell dissemination and metastasis: findings from multiple types of human tumors.
Our previous studies revealed that leukocyte infiltration could trigger human breast and prostate tumor invasion through focal disruptions of the tumor capsule, which selectively favors monoclonal proliferation of tumor progenitors or a biologically more aggressive cell clone overlying the focal disruptions. Our current study, involving multiple types of human tumors, further shows that leukocyte infiltration could also trigger tumor metastasis through the following pathways: [1] more leukocytes migrate to focally disrupted tumor capsules, which forms leukocyte aggregates surrounding newly formed tumor cell clusters, [2] the physical movement of leukocytes into proliferating tumor cells disrupts the intercellular junctions and cell-surface adhesion molecules, causing the disassociation of tumor cells from the tumor core, [3] leukocytes are conjoined with some of these tumor cells through plasma membrane fusion, creating tumor cell-leukocyte chimeras (TLCs), and [4] the leukocyte of TLCs impart migratory capacity to associated tumor cell partners, physically dragging them to different tissue sites. Our findings suggest a novel pathway for tumor cell dissemination from the primary sites and the subsequent journey to new sites. Our findings also provide a unique explanation for the cellular mechanism of leukocytes on tumor invasion and metastasis. If confirmed, our hypothesis and technical approach may significantly facilitate early detection and intervention of tumor invasion and metastasis. Topics: Antigens, CD34; Breast Neoplasms; Collagen Type IV; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Leukocytes; Male; Neoplasm Invasiveness; Neoplasm Metastasis; Prostatic Neoplasms; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms | 2011 |
[Glassy cell carcinoma of cervix: a clinicopathologic analysis of 5 cases].
To investigate the clinicopathological characteristics, histological diagnosis, immunohistochemistry and prognosis of cervical glassy cell carcinoma (GCC).. The clinical characteristics, cytology, histology and immunohistochemistry were analyzed in 5 cases of GCC.. The average age of the five patients was 34.4 years (31 - 41 years). Abnormal vaginal bleeding and/or watery discharge were clinical presentations. One case was complicated with pregnancy and another one had a seven-year history of using contraceptives. All patients had an obvious mass in the cervix. Characteristic morphological features of GCC were present in 2 cases. Morphologically, the tumors consisted of clusters of tumor cells with distinct cell bounders, a large amount of eosinophilic granules in the cytoplasm imparting ground glass appearance, and thin nuclear membrane and prominent nucleoli. Nuclear enlargement and multinucleation were frequently noted. Mitosis and apoptosis were common. Numerous eosinophils and plasma cells were present in the stroma. Immunohistochemically, GCC expressed markers for both squamous cell carcinoma (p63 and CK34βE12) and adenocarcinoma (CAM5.2, MUC1, MUC2 and CEA). Ki-67 proliferation index was high (≥ 70%). All the five patients were treated with radical hysterectomy, followed by radiation and chemotherapy. The tumor-free survival time ranged from 25 days to 33 months.. GCC is a distinct variant of adenosquamous carcinoma of the cervix with high proliferation index and expression of markers of both squamous cell carcinoma and adenocarcinoma. The tumor has characteristic cytological and histological features. Topics: Adult; Biomarkers; Carcinoembryonic Antigen; Carcinoma, Adenosquamous; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Hysterectomy; Immunohistochemistry; Keratins; Ki-67 Antigen; Membrane Proteins; Mucin-1; Pregnancy; Pregnancy Complications, Neoplastic; Radiotherapy, Adjuvant; Uterine Cervical Neoplasms | 2011 |
The two faces of cervical adenocarcinoma in situ.
In order of frequency, cervical intraepithelial neoplasia (CIN), combined adenocarcinoma in situ (AIS)/CIN lesions, and solitary AIS are the most prevalent premalignant lesions of the uterine cervix. As the morphologic distinction of these subtypes is not always straightforward, we performed an immunophenotyping analysis to establish distinguishing profiles for each of these squamous and glandular progenitor lesions of cervical carcinoma. A series of 26 premalignant cervical lesions, comprising 13 cases of AIS, of which 7 represented solitary AIS and 6 were combined with CIN (combined AIS/CIN), as well as 13 solitary high-grade CIN lesions, were immunophenotypically analyzed using antibodies directed against p16, p63, bcl-2, and cytokeratins (CK) 5, 7, 8, 13, 17, 18, and 19. Adjacent normal epithelia were also investigated. CIN lesions expressed the full panel of antibodies. Combined AIS/CIN lesions also expressed the full complement of markers in both the AIS and CIN compartments. However, the expression of p63, bcl-2, CK5, and CK17 was lower in AIS compared with CIN. The solitary AIS lesions could be subdivided into 2 subgroups, 1 expressing the full complement of markers and a second group in which no expression of p63, bcl-2, CK5, and a sporadically CK17 expression was observed. We conclude that 2 phenotypically distinct types of AIS can be identified, that is, AIS with a reserve cell marker phenotype and AIS with an endocervical glandular phenotype. These observations support the view that reserve cells are capable of bidirectional premalignant transformation, that is, into CIN and reserve cell-type AIS, as well as combined AIS/CIN. The endocervical type of AIS is probably a result of the unidirectional transformation of progenitor cells within the glandular cell compartment. Topics: Adenocarcinoma; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Keratins; Proto-Oncogene Proteins c-bcl-2; Retrospective Studies; Tumor Suppressor Proteins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 2010 |
Uterine involvement of malignant mesothelioma detected by analyses of cervicovaginal smear and endometrial biopsy specimens.
Topics: Adult; Calbindin 2; Endometrium; Female; Humans; Keratins; Mesothelioma; Mucin-1; Radiography; S100 Calcium Binding Protein G; Uterine Cervical Neoplasms; Vaginal Smears | 2009 |
Psammoma bodies in cervical smear in association with keratinizing squamous cell carcinoma of cervix: a case report.
The presence of psammoma bodies (PBs) in cervical smears is a rare finding. These structures have been identified in association with a wide range of benign and malignant conditions within the female genital tract. PBs in cervical smears have usually been associated with malignant serous epithelial ovarian tumors. However, many PBs associated with atypical squamous cells were detected in cervical smears of an 83-year-old woman with complaint of postmenopausal bleeding. Colposcopic examination revealed an ulceroinfiltrative growth in the cervix. Histological examination of the biopsy specimen from the growth revealed keratinizing squamous cell carcinoma with multiple and singly arranged PBs. This report suggests that cytologists should aware of the possibilities, on finding PBs associated with atypical cells in cervical specimens and report the cases accordingly. Topics: Aged, 80 and over; Calcinosis; Carcinoma, Squamous Cell; Female; Humans; Keratins; Uterine Cervical Neoplasms; Vaginal Smears | 2009 |
Orbital metastasis of keratinizing squamous cell cervical carcinoma with giant cells. A case report.
A case of orbital metastasis of cervical keratinizing squamous cell carcinoma is presented. The patient, in remission from primary cervical and ovarian cancers, presented with complaints of left eye ptosis and pain. Examination revealed the presence of a moderately tender mass along the left supra-temporal orbital rim and downward displacement of the left globe. Computed tomography revealed a poorly circumscribed mass with superior lateral wall bone loss. Excised tissue contained invasive, poorly differentiated nests of pan keratin and epithelial membrane antigen-positive squamous cells with numerous pleomorphic multinucleated giant cells. Multiple treatment regimes were unsuccessful, and the patient expired due to disease complications after 3 months. Topics: Adult; Carcinoma, Squamous Cell; Fatal Outcome; Female; Giant Cells; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Staging; Orbital Neoplasms; Tomography, X-Ray Computed; Uterine Cervical Neoplasms | 2009 |
[A rare cervical tumor].
Topics: Aged; Eosinophils; Female; Humans; Keratins; Uterine Cervical Neoplasms; Vacuoles | 2008 |
Histopathological and immunohistochemical (cytokeratins AE1/AE3) study of the parametrium of patients with early stage cervical cancer.
This study was undertaken in order to evaluate histopathological and immunohistochemical (cytokeratins AE1/AE3) characteristics of parametrial invasion in patients with early stage cervical cancer.. Thirty patients with stage IB squamous cell carcinoma (SCC) of the cervix submitted to radical hysterectomy from November 2001 to September 2002 were prospectively studied. Histopathological studies were undertaken using tissue samples (n=60) taken from the parametrium, whose surgical margins were inked and the entire parametrial tissue was fixed in 10% buffered formalin and embedded in paraffin for further analysis using hematoxylin-eosin (H&E) staining. Specific patterns of parametrial involvement (continuous invasion, parametrial lymphatic vascular space invasion (LVSI) and/or parametrial lymph nodes' (PMLN) metastasis) were recorded. Parametrial samples, in which the histological examination showed no tumor involvement, were immunohistochemically assessed through monoclonal antibodies for cytokeratins AE1/AE3. Clinicopathological characteristics of the patients were also recorded.. Patient's mean age was 49+/-10 years (27-73 years). Histopathological analysis (H&E) showed parametrium involvement in 12 patients (40%) of whom 11 (92%) presented parametrial LVSI, 9 (75%) continuous invasion and 4 (33%) PMLN metastasis. Micrometastasis was detected in 3/18 (17%) of the patients with histologically negative parametrium by H&E evaluation. Parametrial involvement detected by H&E was associated with tumor recurrence (p=0.009) and survival (p=0.025). This association was not correlated with the presence of parametrial micrometastasis (p=1.00 and 1.00, respectively).. The process of parametrial spreading in patients with SCC of the cervix may develop several histopathological patterns, which are associated with clinicopathological features and prognosis. Our findings highlight the importance to ink the parametria, which is the only way to define the pattern of tumor spreading. The clinical significance of micrometastasis, detected in patients with histologically negative parametrium by H&E, remains to be clear. Topics: Adult; Carcinoma, Squamous Cell; Connective Tissue; Female; Humans; Keratins; Middle Aged; Pelvic Floor; Pelvic Neoplasms; Prospective Studies; Sentinel Lymph Node Biopsy; Survival Analysis; Uterine Cervical Neoplasms | 2008 |
Morphological effects of radiochemotherapy on cervical carcinoma: a morphological study of 50 cases of hysterectomy specimens after neoadjuvant treatment.
The introduction of radiochemotherapy for treatment of advanced cervical cancers represents a new chapter in surgical pathology. The study group included 50 women with a histological diagnosis of advanced cervical carcinoma (43 squamous, 3 adenosquamous, 2 adenocarcinoma, 1 glassy cell, and 1 undifferentiated; International Federation of Gynecology and Obstetrics stage Ib-III) receiving a platinum-based chemotherapy concomitant with external beam radiotherapy before radical surgery. We evaluated the amount of residual neoplastic tissue, depth of invasion, presence of neoplastic embolism, number of metastatic lymph nodes, and alterations of the nonneoplastic stroma and epithelium. We observed neoplastic masses larger than 0.3 cm (no pathological response, pR2) in 14 cases (28%), single or multiple microscopic neoplastic residual (partial pathological response, pR1) in 24 cases (48%), and no invasive neoplastic cells (complete pathological response, pR0) in 12 cases (24%). Residual neoplastic cells showed a wide pattern of alterations such as cytoplasmic eosinophilia, vacuolation, and foamy appearance; the nuclei were enlarged and irregular with clumped chromatin. The mitotic activity was scanty. In some cases, multinucleated neoplastic giant cell coexisted with reactive foreign body-like giant cells. The stroma was fibrous containing inflammatory cells, fibrinous debris, cholesterol clefts, hemosiderin pigments, and microcalcifications. In just 2 cases, we found lymph node metastases. The pathologist has to distinguish neoplastic residuals from reactive changes. In most cases, morphological criteria are sufficient to make a diagnosis, but sometimes, the use of immunohistochemistry (keratins and CD68) is a mandatory method to reveal the nature of the lesion. Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoma; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Cervix Uteri; Combined Modality Therapy; Female; Humans; Hysterectomy; Keratins; Middle Aged; Neoadjuvant Therapy; Uterine Cervical Neoplasms | 2008 |
A combination of serum tumor markers identifies high-risk patients with early-stage squamous cervical cancer.
We aimed to investigate whether pretreatment serum levels of squamous cell carcinoma (SCC) antigen (SCC-Ag), cytokeratin 19 (CYFRA 21-1) and two mucins (CA 15-3 and CA 125) identify patients with occult disease in early-stage SCC of the cervix. Therefore, pretreatment serum samples were obtained from 78 patients with SCC of the cervix (52 IB, 9 IIA and 18 IIB), and tumor markers were measured with commercial immunoassays. SCC-Ag, CYFRA 21-1 and CA 15-3 (analyzed as continuous variables) were significantly associated with overall (OS) and disease-free survival (DFS) in univariate analysis (p < 0.001 in all cases). Multivariate analysis identified lymph node status as the strongest predictor for OS and DFS (p < 0.001 and p = 0.001, respectively), followed by CYFRA 21-1 (p = 0.060 and p = 0.027, respectively) and CA 15-3 (p = 0.082 and p = 0.017, respectively). Clinical cutoff values for each marker were defined by maximizing the log-rank statistics for OS in the total population: 1.1 microg/l for SCC-Ag (n = 47, 60.3%), 1.4 microg/l for CYFRA 21-1 (n = 47, 60.3%), 40 U/ml for CA 15-3 (n = 11, 14.1%) and 30 U/ml for CA 125 (n = 10, 12.8%). Stage IB patients with positive SCC-Ag and CYFRA 21-1 had significantly lower OS (mean 8.3 years, 95% confidence interval, CI, 5.8-10.7 years) and DFS (mean 7.3 years, 95% CI 4.6-10 years) than all other stage IB patients (OS, mean 14.5 years, 95% CI 13.5-15.5 years; DFS, mean 13.9 years, 95% CI 12.5-15.4 years). Stage IB patients with tumors <4 cm or with negative lymph nodes and positive SCC-Ag and CYFRA 21-1 had significantly poorer OS and DFS compared to all other patients in the same group. Elevated levels of both CA 125 and CA 15-3 (3 patients) were associated with an extremely poor prognosis. In conclusion, a combination of SCC-Ag and CYFRA 21-1 may help to identify early-stage cervical cancer patients with occult disease requiring adjuvant therapy. Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Middle Aged; Mucin-1; Neoplasm Staging; Prognosis; Risk; Serpins; Uterine Cervical Neoplasms | 2008 |
Biochemical prognostic factors and risk of relapses in patients with cervical cancer.
No validated tumor marker is currently available for the management of patients with cervical cancer. However, some tumor-associated antigens have been measured in the sera from patients with this malignancy and have been related to the clinical course of disease. Squamous cell carcinoma antigen (SCC) is more sensitive than CYFRA 21-1 for squamous cell cervical cancer. Serum SCC levels are elevated in 28-88% of patients with this malignancy, and correlate with tumor stage, tumor size, cervical stromal invasion, lymph-vascular space involvement, and lymph node status. Some authors reported that pre-treatment serum SCC has no prognostic value, whereas others found that it is related to disease-free survival and/or overall survival at univariate analysis or at multivariate analysis. Serial SCC measurements correlate with tumor response to radiotherapy and/or chemotherapy and the clinical outcome of patients. Increasing serum SCC can precede the clinical diagnosis of relapse in 46-92% of cases, with a median lead time ranging from 2 to 8 months. According to some authors serum SCC assay during the follow-up does not improve the cure rate of patients who will ultimately develop a recurrence. However, it has been recently reported that the performance of a PET in asymptomatic patients with serum SCC elevation can sometimes allow an earlier diagnosis of relapse with a survival benefit. Serum CA 125 levels are raised in 20-75% of patients with cervical adenocarcinoma, and reflect tumor stage, tumor size, histological grade, cervical stromal invasion, lymph-vascular space involvement, and lymph node status. Pre-treatment CA 125 levels appear to have a prognostic value, and rising serum CA 125 may precede or be coincident with the clinical diagnosis of recurrent cervical adenocarcinoma. Topics: Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; Female; Humans; Keratin-19; Keratins; Neoplasm Staging; Prognosis; Risk Factors; Serpins; Uterine Cervical Neoplasms | 2007 |
Paradoxical antiproliferative effect by a murine mammary tumor-derived epithelial cell line.
Despite significant advancement in breast cancer therapy, there is a great need for a better understanding of the mechanisms involved in breast carcinogenesis and progression, as well as of the role of epigenetic contributions from stromal cells in mammary tumorigenesis. In this study, we isolated and characterized murine mammary tumor-derived epithelial and myofibroblast cell lines, and investigated the in vitro and in vivo effect of cellular soluble factors produced by the epithelial cell line on tumor cells.. Morphology, immunophenotype, cytogenetics, invasiveness, and tumorigenicity of epithelial (LM-234ep) and myofibroblast (LM-234mf) cell lines isolated from two murine mammary adenocarcinomas with common ancestor were studied. The in vitro effects of LM-234ep conditioned medium on proliferation, cell cycle distribution, and expression of cell cycle proteins, were investigated in LM-234mf cells, mouse melanoma cells (B16-F10), and human cervical adenocarcinoma cells (HeLa). The in vivo anti-tumor activity of LM-234ep conditioned media was evaluated in subcutaneous tumors formed in nude mice by B16-F10 and HeLa cells.. LM-234ep cells were found to be cytokeratin positive and hipertriploid, whereas LM-234mf cells were alpha-smooth muscle actin positive and hypohexaploid. Chromosome aberrations were found in both cases. Only LM-234mf revealed to be invasive in vitro and to secrete active MMP-2, though neither of the cell types were able to produce progressing tumors. LM-234ep-derived factors were able to inhibit the in vitro growth of LM-234mf, B16-F10, and HeLa cells, inducing cell cycle arrest in G0/G1 phase. The administration of LM-234ep conditioned medium inhibited the growth of B16-F10 and HeLa tumors in nude mice.. Our data suggest the existence of epithelial cell variants with tumor suppressive properties within mammary tumors. To our knowledge, this is the first report showing antiproliferative and antineoplastic activities induced by tumor-derived epithelial cells. Topics: Actins; Adenocarcinoma; Animals; Carcinogenicity Tests; Cell Line, Tumor; Cell Proliferation; Chromosome Aberrations; Culture Media, Conditioned; Epithelial Cells; Female; Gelatinases; Humans; Keratins; Mammary Neoplasms, Experimental; Melanoma; Mice; Mice, Inbred BALB C; Paracrine Communication; Uterine Cervical Neoplasms | 2007 |
Giant cell carcinoma of the uterine cervix: a case report.
Topics: Aged; Biomarkers; Carcinoma, Giant Cell; Female; Humans; Immunohistochemistry; Keratins; Mucin-1; Uterine Cervical Neoplasms | 2006 |
Histopathological and immunohistochemical aspects in both basaloid and spindle cell variant of cervical carcinoma.
The study was performed by using a number of eight cases of cervical carcinomas suiting to basaloid carcinomas and spindle cell carcinomas under the circumstances of usual histopathological staining. Immunohistochemically we used anticytokeratin monoclonal antibody (AE1/AE3) to confirm the epithelial differentiation and also PCNA to evaluate the cell proliferation rate. Tumor positiveness for AE1/AE3 cytokeratin cocktail confirmed its epithelial nature. Immunoexpression for PCNA indicated a high index of cell proliferation for all the cases with a more increased value for the basaloid carcinomas. Topics: Adult; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Proliferating Cell Nuclear Antigen; Uterine Cervical Neoplasms | 2006 |
Cytokeratins 7 and 20 in primary and secondary mucinous tumors of the ovary: analysis of coordinate immunohistochemical expression profiles and staining distribution in 179 cases.
Coordinate expression profiles for cytokeratins 7 and 20 (CK7 and CK20) are useful for distinguishing certain types of adenocarcinomas but use for distinction of primary and secondary mucinous tumors in the ovary is limited due to the existence of a number of tumor types exhibiting overlapping CK7/CK20 immunoprofiles; the use of staining distribution patterns in the distinction of tumors with shared profiles has not been evaluated in detail. We report analysis of both coordinate expression profiles and staining distribution in 179 rigorously classified mucinous tumors in the ovary, including 53 primary tumors [35 atypical proliferative (borderline) mucinous tumors of gastrointestinal type and 18 invasive mucinous carcinomas] and 126 secondary tumors [28 colorectal adenocarcinomas, 54 appendiceal tumors (23 adenocarcinomas, 31 low-grade adenomatous mucinous tumors associated with pseudomyxoma peritonei), 14 pancreatic adenocarcinomas, 8 endocervical adenocarcinomas, 5 gastric adenocarcinomas, 4 gallbladder/biliary tract adenocarcinomas, and 13 adenocarcinomas of unknown primary sites). A CK7+/CK20+ immunoprofile was the most common profile in primary ovarian tumors (74%), upper gastrointestinal tract tumors (78%), and endocervical tumors (88%) but was occasionally observed in lower intestinal tract tumors (colorectal: 11%; appendiceal: 13% of low-grade tumors, 35% of carcinomas). A CK7-/CK20+ immunoprofile was the most common profile in lower intestinal tract tumors (79%) and was uncommon in upper gastrointestinal tract tumors (9%), rarely seen in primary ovarian tumors (4%), and not seen in endocervical tumors. A CK7+/CK20- profile was observed in some primary ovarian (23%), upper gastrointestinal tract (13%), and endocervical tumors (13%) but not in lower intestinal tract tumors. For CK7+ tumors, staining distribution was very frequently diffuse (>50% of tumors cells positive) in primary ovarian, upper gastrointestinal tract, and endocervical tumors, whereas staining distribution was often focal (<50% of tumors cells positive) when present in colorectal and appendiceal carcinomas but not in low-grade appendiceal tumors. For CK20+ tumors, staining distribution was variable but often focal in primary ovarian tumors and nonlower intestinal tract tumors, whereas the pattern was almost always diffuse in lower intestinal tract tumors. Immunohistochemical staining distribution can supplement CK7/CK20 coordinate expression profiles to distinguish subsets of prim Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Coloring Agents; Female; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Pseudomyxoma Peritonei; Uterine Cervical Neoplasms | 2006 |
Distribution of HPV infection and tumour markers in cervical intraepithelial neoplasia from cone biopsies of Mozambican women.
To evaluate human papillomavirus (HPV) infection in whole cervical cone specimens with cervical intraepithelial neoplasia (CIN). In addition, to evaluate the relation between the presence of CIN lesions and HPV infection and the expression of Ki-67, p53, cytokeratins, Gp230 glycoprotein, and simple mucin-type carbohydrates.. Cervical cone specimens from five patients with CIN were studied. For each specimen, serial sections encompassing the whole cone were collected (52 samples). HPV infection and HPV types were detected by the polymerase chain reaction and enzyme immunoassay. The expression of Ki-67, p53, cytokeratins, Gp230, and simple mucin-type carbohydrates was examined immunohistochemically.. All cases showed high risk HPV types, namely types 16, 33, 35, and 58. Four of the five patients were infected by multiple viral types. HPV-58 was always seen in CIN III, whereas HPV-35 was more frequent in CIN I. The expression of Ki-67 and p53 was higher in CIN III lesions. The expression of cytokeratins 8 and 17 showed complete or almost complete overlap with CIN III. Altered expression of Gp230, Tn, and sialyl-T was often seen in all grades of CIN.. When whole cervical cone specimens are evaluated the rate of multiple HPV infection is very high. The expression of cytokeratins 8 and 17 is a useful marker of CIN III. Topics: Biomarkers, Tumor; Biopsy; Female; Humans; Immunoenzyme Techniques; Keratins; Ki-67 Antigen; Mozambique; Neoplasm Proteins; Papillomaviridae; Papillomavirus Infections; Polymerase Chain Reaction; Tumor Suppressor Protein p53; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 2005 |
Keratin profiling studies in the differential diagnosis of carcinomas.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Epithelial Cells; Female; Humans; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 2005 |
High-resolution multi-parameter DNA flow cytometry enables detection of tumour and stromal cell subpopulations in paraffin-embedded tissues.
The accuracy of DNA ploidy measurements of paraffin-embedded tissues is limited by the lack of resolution and the inability to identify the DNA diploid population unequivocally in bimodal DNA histograms. A multi-parameter DNA flow cytometric method has been developed that enables the simultaneous detection of neoplastic and stromal cells in samples from dewaxed 50 microm sections or 2 mm diameter punches of archival tissue blocks. The method combines heat pretreatment in sodium citrate buffer and subsequent enzymatic dissociation with a collagenase/dispase mixture. Cells were simultaneously stained for keratin (FITC), vimentin (R-PE), and DNA (PI) before flow cytometric analysis. The method was applied to 12 paraffin-embedded cervical carcinomas and four colorectal carcinomas. In all cervical cancers, distinct keratin-positive and vimentin-positive cell populations were observed. While the exclusive vimentin-positive cell fractions always yielded unimodal DNA content distributions, bimodal distributions were observed for the keratin-positive cell fractions in nine cervical carcinomas, whereas one cervical carcinoma showed three distinct G0G1 populations. Coefficients of variation of the G0G1 peaks ranged from 1.70% to 4.79%. Average background, aggregate, and debris values were 14.7% (vimentin-positive fraction) and 33.8% (keratin-positive fraction). Flow sorting confirmed that the exclusively vimentin-positive cell fractions represent different normal stromal and infiltrate cells that can serve as an internal ploidy reference enabling discrimination between DNA hypo-diploid and DNA hyper-diploid tumour cell subpopulations. The neoplastic origin of the keratin-vimentin co-expressing cells from two cervical carcinomas was confirmed by genotyping of flow-sorted samples revealing loss of heterozygosity (LOH) of 6p. This improved method obviates the need for fresh/frozen tumour tissue for high-resolution DNA ploidy measurements and enables the isolation of highly purified tumour subpopulations for subsequent genotyping. Topics: Antibodies, Monoclonal; Colorectal Neoplasms; DNA, Neoplasm; Female; Flow Cytometry; Formaldehyde; Hot Temperature; Humans; Keratins; Loss of Heterozygosity; Neoplasm Proteins; Paraffin Embedding; Ploidies; Stromal Cells; Tissue Fixation; Uterine Cervical Neoplasms; Vimentin | 2005 |
Gene expression profile of cervical tissue compared to exfoliated cells: impact on biomarker discovery.
Exfoliated cervical cells are used in cytology-based cancer screening and may also be a source for molecular biomarkers indicative of neoplastic changes in the underlying tissue. However, because of keratinization and terminal differentiation it is not clear that these cells have an mRNA profile representative of cervical tissue, and that the profile can distinguish the lesions targeted for early detection.. We used whole genome microarrays (25,353 unique genes) to compare the transcription profiles from seven samples of normal exfoliated cells and one cervical tissue. We detected 10,158 genes in exfoliated cells, 14,544 in the tissue and 7320 genes in both samples. For both sample types the genes grouped into the same major gene ontology (GO) categories in the same order, with exfoliated cells, having on average 20% fewer genes in each category. We also compared microarray results of samples from women with cervical intraepithelial neoplasia grade 3 (CIN3, n = 15) to those from age and race matched women without significant abnormalities (CIN1, CIN0; n = 15). We used three microarray-adapted statistical packages to identify differential gene expression. The six genes identified in common were two to four fold upregulated in CIN3 samples. One of these genes, the ubiquitin-conjugating enzyme E2 variant 1, participates in the degradation of p53 through interaction with the oncogenic HPV E6 protein.. The findings encourage further exploration of gene expression using exfoliated cells to identify and validate applicable biomarkers. We conclude that the gene expression profile of exfoliated cervical cells partially represents that of tissue and is complex enough to provide potential differentiation between disease and non-disease. Topics: Biomarkers; Biomarkers, Tumor; Cervix Uteri; Computational Biology; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic Markers; Genome, Human; Genomics; Humans; Keratins; Oligonucleotide Array Sequence Analysis; RNA, Messenger; Software; Transcription, Genetic; Up-Regulation; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 2005 |
Cytologic features of high-grade squamous intraepithelial lesion in conventional slides: what is the difference between cases that perform well and those that perform poorly?
Previous studies have suggested that cases of high-grade squamous intraepithelial lesion in conventional smears and in ThinPrep specimens that are frequently misinterpreted as normal have relatively few small and hypochromatic dysplastic cells.. To determine the cytologic differences between conventional Papanicolaou slides of high-grade squamous intraepithelial lesion that perform poorly and those that perform well.. We compared the cytologic features of 22 cases of conventional smears with high-grade squamous intraepithelial lesion that performed poorly in the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology with 45 cases of conventional smears that performed extremely well.. Cases that performed poorly were significantly more likely to have 50 or fewer single dysplastic cells (P = .003) and to have only small dysplastic cells (P = .01). Cases that performed well were also more likely to have more than 500 dysplastic cells (P = .002), to exhibit the presence of large dysplastic cells (P < .001), and to be keratinized (P = .03). Hypochromasia and the number of groups of dysplastic cells were not correlated with performance.. Conventional smears with high-grade squamous intraepithelial lesion with 50 or fewer single dysplastic cells, no large dysplastic cells, and lacking keratinization are highly associated with poor performance in this program. Topics: Carcinoma, Squamous Cell; Cell Count; Diagnostic Errors; Female; Humans; Keratins; Papanicolaou Test; Pathology, Clinical; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears | 2005 |
Detection of microinvasion in vulvar and cervical intraepithelial neoplasia using double immunostaining for cytokeratin and basement membrane components.
Identification of early invasion in vulvar intraepithelial neoplasia 3 (VIN 3) and cervical intraepithelial neoplasia 3 (CIN 3) may be difficult with the use of routine hematoxylin-eosin staining. Presence of obscuring inflammation and tangential tissue sectioning are the most common diagnostic pitfalls.. To examine the utility of double immunostaining for cytokeratin-collagen IV or cytokeratin-laminin in the detection of early invasion in VIN 3 and CIN 3.. The study group consisted of 10 cases of "VIN 3, suspicious for invasion" and 10 cases of "CIN 3, suspicious for invasion." The negative control group consisted of VIN 3 (n = 15) and CIN 3 (n = 10). The positive control group consisted of cases of invasive vulvar carcinoma (n = 11) and invasive cervical carcinoma (n = 25). All cases were double immunostained for cytokeratin and collagen IV and, in a separate reaction, for cytokeratin and laminin. The continuity of the basement membrane and the presence of stromal invasion were assessed in the stained sections.. The staining for collagen IV and laminin yielded identical results. A well-defined, continuous basement membrane was visualized in all cases of VIN 3 and CIN 3. A discontinuous or absent basement membrane was observed around the malignant cells on the invasive tumor front in all cases of vulvar and cervical carcinoma. In 2 of 10 cases of VIN 3, suspicious for invasion and in 4 of 10 cases of CIN 3, suspicious for invasion definitive foci of microinvasion were identified with the use of double immunostaining. A well-defined, continuous basement membrane was present in the remaining cases "suspicious for invasion.". Double immunostaining for cytokeratin- collagen IV or cytokeratin-laminin is useful for evaluation of early invasion in equivocal cases of VIN 3 and CIN 3. Topics: Adenocarcinoma; Basement Membrane; Biomarkers, Tumor; Collagen Type IV; Female; Humans; Keratins; Laminin; Neoplasm Invasiveness; Retrospective Studies; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vulvar Neoplasms | 2005 |
Adenoid basal carcinoma of the uterine cervix: report of two cases with reference to adenosquamous carcinoma.
Adenoid basal carcinoma (ABC) of the uterine cervix is a rare neoplasm with excellent prognosis. Differential diagnosis between ABC and an ABC-like lesion of adenosquamous cell carcinoma (ASC) of the cervix is important due to their contrasting prognosis. Reported herein are two cases of ABC that have been compared with seven ASC exhibiting ABC-like lesions from approximately 2600 resected uterine cervical malignancies diagnosed at Shikoku Cancer Center. The two ABC were incidentally found in the uterine cervix of 69-year-old and 59-year-old Japanese women due to cervical intraepithelial neoplasia grade 3 and to squamous cell carcinoma, respectively. The ABC consisted of infiltrating nests of basaloid cells with low nuclear atypia. The patients remained alive without recurrence for 9 years and 18 months, respectively. An ABC-like lesion was defined as basaloid cell nests simulating ABC, but with some features indicating malignant potential. However, the differential diagnosis was sometimes difficult because two of seven ABC-like lesions were originally diagnosed as ABC. Immunohistochemically, cytokeratin 7 was negative for the basaloid cells of two ABC, but positive for six of six ABC-like lesions of ASC, while cytokeratin 8 was positive for both ABC and ASC. This cytokeratin pattern might provide a good tool for distinguishing between ABC and an ABC-like lesion of ASC when the histological findings are equivocal. Topics: Adult; Aged; Carcinoma, Adenoid Cystic; Carcinoma, Adenosquamous; Carcinoma, Basal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratin-8; Keratins; Ki-67 Antigen; Middle Aged; Uterine Cervical Neoplasms | 2005 |
Occult tumor cells in pelvic lymph nodes and parametrial tissue of small-sized FIGO IB1 squamous cell carcinomas of the uterine cervix--results of a pilot study.
Micrometastases (MM) and occult tumor cell deposits (OTCD) in pelvic tissue may cause recurrences, and immunohistochemistry may improve their detection. We used cytokeratine-immunohistochemistry to investigate 263 pelvic lymph nodes and parametrial tissue for MM and OTCD obtained from eight squamous cell carcinomas (maximum tumor size: 2.5 cm). These patients were treated with radical abdominal hysterectomy (Piver type III) with complete tumor resection without receiving any adjuvant therapy. The mean count of resected pelvic lymph nodes was 32.9 (range 24-47). All lymph nodes were completely embedded, and three step sections were performed for routine histopathologic evaluation. Three patients developed pelvic side wall and five central tumor recurrences within a median time of 25.9 (range 8-55) months. On immunohistochemistry, only one case (12.5%) showed OTCD in a venule in the parametrial tissue. In patients with small cervical carcinomas (< 2.5 cm in largest dimension), OTCD can only rarely be detected by immunohistochemistry after careful handling of resected lymph nodes using step sectioning for routine histologic examination and complete processing of parametrial pelvic tissue. Therefore, tumor recurrence in those patients appears to be due to occult residual tumor cells that were not resected during the classical Wertheim-Meigs-procedure or that were disseminated during the surgical procedure and persisted in situ. Topics: Adult; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Pelvis; Pilot Projects; Uterine Cervical Neoplasms | 2005 |
Comparison of pre-treatment CYFRA 21 - 1 and SCC-Antigen assay in primary cervical carcinoma - a preliminary report.
CYFRA21 - 1, a fragment of cytokeratin19, has been widely assessed as a serum marker of squamous malignancies. Previous studies using CYFRA21 - 1 and SCC-Antigen have shown mixed results but have indicated a better predictive prognostic value for SCC-Ag as compared to CYFRA21-1. The aim of our prospective, observational, pilot study was to evaluate the role of CYFRA21-1 and SCC-Ag in primary cervical carcinoma. Pre-operative serum CYFRA21-1 and SCC-Ag were measured (n = 14) in women with cervical carcinoma and correlated with staging, clinico-pathological parameters and prognostic data. Logistic regression analysis with CYFRA 21 - 1 test status (positive or negative) as a dependent variable showed that nodal metastases (p = 0.001) and lymphovascular space invasion (LVSI) (p = 0.005) were significant predictors, whereas stage and SCC-Ag levels were not significant. There was also no statistically significant correlation between SCC-Ag and CYFRA21-1 levels. If larger studies confirm these preliminary results, the option of laparoscopic surgical staging in patients with raised CYFRA21-1 levels could be considered. Topics: Adenocarcinoma; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Lymphatic Metastasis; Middle Aged; Pilot Projects; Predictive Value of Tests; Prognosis; Prospective Studies; Serpins; Uterine Cervical Neoplasms | 2005 |
Functional analysis of the human papillomavirus type 16 E1=E4 protein provides a mechanism for in vivo and in vitro keratin filament reorganization.
High-risk human papillomaviruses, such as human papillomavirus type 16 (HPV16), are the primary cause of cervical cancer. The HPV16 E1=E4 protein associates with keratin intermediate filaments and causes network collapse when expressed in epithelial cells in vitro. Here, we show that keratin association and network reorganization also occur in vivo in low-grade cervical neoplasia caused by HPV16. The 16E1=E4 protein binds to keratins directly and interacts strongly with keratin 18, a member of the type I intermediate-filament family. By contrast, 16E1=E4 bound only weakly to keratin 8, a type II intermediate-filament protein, and showed no detectable affinity for the type III protein, vimentin. The N-terminal 16 amino acids of the 16E1=E4 protein, which contains the YPLLXLL motif that is conserved among supergroup A viruses, were sufficient to target green fluorescent protein to the keratin network. When expressed in the SiHa cervical epithelial cell line, the full-length 16E1=E4 protein caused an almost total inhibition of keratin dynamics, despite the phosphorylation of keratin 18 at serine 33, which normally leads to 14-3-3-mediated keratin solubilization. Mutant 16E1=E4 proteins which lack the LLKLL motif, or which have lost amino acids from their C termini, and which were compromised in the ability to associate with keratins did not disturb normal keratin dynamics. 16E1=E4 was found to exist as dimers and hexamers, whereas a C-terminal deletion mutant (16E1=E4Delta87-92) existed as monomers and formed multimeric structures only poorly. Considered together, our results suggest that by associating with keratins through its N terminus, and by associating with itself through its C terminus, 16E1=E4 may act as a keratin cross-linker and prevent the movement of keratins between the soluble and insoluble compartments. The increase in avidity associated with multimeric binding may contribute to the ability of 16E1=E4 to sequester its cellular targets in the cytoplasm. Topics: Culture Techniques; Cytoskeleton; Female; Humans; Intermediate Filaments; Keratins; Oncogene Proteins, Fusion; Papillomaviridae; Papillomavirus Infections; Tumor Cells, Cultured; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Viral Proteins | 2004 |
[Clinical significance of sentinel lymph nodes detection in patients with early stage cervical cancer].
To study the value of sentinel lymph nodes (SLN) in prediction of the pelvic lymph nodes status and to determine the significance of SLN detection in pelvic lymph nodes dissection in patients with early stage cervical carcinoma.. From November 2002 to August 2003, 23 patients with early stage cervical carcinoma planned to undergo radical hysterectomy and extensive pelvic lymph nodes dissection received an intracervical injection of technetium-labeled sulfur colloid as well as blue dye to identify and perform resection of SLNs. The SLNs were pathologically compared with non-SLNs with frozen section, paraffin section, and anti-cytokeratin immunohistochemical staining.. Out of 23 patients, SLNs were detected in 19 patients. A total of 59 SLNs were identified and the mean was 3 per patient. The detection rate of SLN was 83%. Sensitivity, specificity and accuracy of the SLN biopsy were 83%, 100% and 95%, respectively.. SLNs detection can predict the pelvic lymph nodes status in early stage cervical carcinoma, but the feasibility and safety of this technique to substitute conventional surgical modality should be evaluated by large series of prospective studies. Topics: Adult; Female; Humans; Hysterectomy; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Middle Aged; Neoplasm Staging; Pelvis; Sentinel Lymph Node Biopsy; Uterine Cervical Neoplasms | 2004 |
Detection of pelvic lymph node micrometastasis in stage IA2-IB2 cervical cancer by immunohistochemical analysis.
The objectives of this study were to (1) determine the incidence of lymph node micrometastasis in cervical cancer by immunohistochemical analysis and (2) determine if the presence of micrometastasis is a poor prognostic feature in early cervical cancer.. We retrospectively reviewed the medical records of 62 patients who underwent radical hysterectomy and lymphadenectomy for FIGO stage IA2-IB2 cervical cancer at Stanford University Hospital from 1990 to 2000. Forty-nine patients with negative lymph nodes were identified. A total of 976 formalin-fixed paraffin-embedded pelvic lymphadenectomy specimens were serially sectioned and stained with anti-cytokeratin antibodies AE1 and AE1/CAM5.2.. Six patients had stage IA2 disease, 37 had stage IB1, and 6 had IB2. The mean age of the patients was 44 years (range, 24-76). Seventy-one percent had squamous cell carcinomas, 22% had adenocarcinomas, and 6% had other types. Lymph node micrometastases were immunohistochemically detected in 4 of the 49 (8.1%) patients, comprising 4 of 976 (0.41%) pelvic lymph nodes examined. Twelve of 45 (15.6%) patients with negative nodes had lymph-vascular space invasion (LVSI) whereas 3 of 4 (75%) patients with micrometastases had LVSI. At a mean follow-up time of 39.4 months, 2 of 4 (50%) patients with micrometastasis had recurrent disease, while 3 of 45 (6.7%) patients without micrometastasis developed recurrent disease.. These preliminary data suggest that immunohistochemical detection of pelvic lymph nodes is more frequent in patients with LVSI and may identify patients needing adjuvant chemoradiation. Topics: Adult; Aged; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Uterine Cervical Neoplasms | 2004 |
Keratinocyte-specific POU transcription factor hSkn-1a represses the growth of cervical cancer cell lines.
The POU transcription factor human Skn-1a (hSkn-1a) specifically promotes the proliferation of keratinocytes and enhances their differentiation. We examined the effects of hSkn-1a on cervical cancer cell lines of epithelial origin, in which the differentiation program is interrupted. From HeLa/Tet-On, a clone that can be induced to make hSkn-1a by doxycycline (HeLa/hSkn-1a) was prepared and characterized. Shortly after the induction, the cells expressed cytokeratin 10 (K10), a major marker protein in differentiating keratinocytes. While maintained for several days in the presence of doxycycline, the HeLa/hSkn-1a cells showed a slightly prolonged time of population doubling, the occasional appearance of flat cells with lowered DNA synthesis, and a low level of apoptotic DNA fragmentation. In SiHa and HeLa S3 cultures, K10 mRNA and apoptotic DNA fragmentation were detected at 48 h after infection with an adenoviral vector capable of expressing hSkn-1a. A colony inhibition assay showed that the growth of HeLa S3, SiHa, CaSki, and C-33A cells was repressed, as seen from the decreased number and average size of the drug-resistant colonies at 2 or 3 weeks after transfection with a plasmid that can express hSkn-1a and neomycin resistance gene. These results suggest that the expression of hSkn-1a represses the growth of the cervical cancer cells through the partial resumption of the differentiation pathway followed by slow suppression of cell replication and apoptosis. Topics: Apoptosis; Cell Differentiation; Cell Division; Cell Line, Tumor; Doxycycline; Female; HeLa Cells; Humans; Keratinocytes; Keratins; Transfection; Uterine Cervical Neoplasms | 2004 |
Keratins 8, 10, 13, and 17 are useful markers in the diagnosis of human cervix carcinomas.
Several candidate tumor markers for cervical neoplasia have been identified. Among those are keratin markers, whose precise implications in the diagnosis are still under debate. In the present study, we aimed to clarify the usefulness of studying the expression of keratins 8, 10, 13, and 17 for diagnostic purposes in human cervix carcinomas. Forty-four invasive squamous carcinomas, 10 cervical intraepithelial neoplasia grade III (CIN III), and 10 reference cervix were examined immunohistochemically with monoclonal antibodies. Expression of keratins in reference exocervix, CIN III, and invasive carcinomas was as follows: keratin 8--0, 44.4%, and 57.1%, respectively; keratin 10-77.8%, 40%, and 19%, respectively; keratin 13--100%, 22.2%, and 25%, respectively; keratin 17-0, 40%, and 73.2%, respectively. In invasive carcinomas, expression of keratin 10 was significantly associated with keratinizing carcinomas. In conclusion, we observed that expression of keratins 8 and 17 and loss of keratins 10 and 13 are good markers of malignant transformation in human cervix. Keratin expression patterns, namely expression of keratin 10, can be useful for subtyping and grading squamous cell carcinomas of the cervix. Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Sensitivity and Specificity; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 2004 |
Identification of micrometastases in histologically negative lymph nodes of early-stage cervical cancer patients.
Despite histologically negative lymph nodes, approximately 15% of patients with early-stage cervical cancer will develop recurrence. Micrometastases have been shown to be important in staging and treatment of breast cancers and melanoma and have been identified by polymerase chain reaction analysis in cervical cancers. This study sought to estimate the frequency of micrometastases identified by immunohistochemistry in histologically negative lymph nodes and compare this to other known risk factors for recurrence of cervical cancer.. Early-stage (stages IA2, IB1, and IB2) cervical cancer patients of all histologic subtypes were identified from the surgical logs of the Los Angeles County-University of Southern California Medical Center for the period 1994-2000. One hundred thirty-two patients had histologically negative lymph nodes. Immunohistochemical assay was performed on 3,106 lymph nodes by using antibodies against cytokeratins AE-1 and CAM 5.2 in combination according to standard protocols. The stained nodes were then evaluated for the presence of micrometastases and compared against the respective clinicopathologic information in each case.. Micrometastases were detected in 19 of 132 (15%, 95% confidence interval [CI] 9%, 22%) patients, found in 29 of the 3,106 (0.9%) lymph nodes evaluated. Vascular space invasion was seen in 50 of 132 cases (38%, 95% CI 30%, 47%) and in 8 of 19 (42%, 95% CI 21%, 66%) cases with micrometastases. Surgical margins of the resected specimen were negative in 120 of 132 cases (91%, 95% CI 84%, 95%) and in 16 of 19 (84%, 95%CI 60%, 96%) of those cases with micrometastases. Micrometastases were seen most frequently in pelvic lymph nodes (25 of 29, 86%). Patients with more than 20 lymph nodes removed were more likely to demonstrate metastasis (P <.001). There was no statistically significant association between micrometastasis and vascular space invasion or tumor volume.. Micrometastases are identifiable in histologically negative lymph nodes in 15% (95% CI 9%, 22%) of early-stage cancer patients, a frequency which approximates the recurrence rate for patients with negative nodes. In this series, patients with greater numbers of lymph nodes analyzed were more likely to have lymph node micrometastasis identified. There appears to be no relationship between tumor volume and the identification of micrometastases. Although micrometastases can be identified in histologically negative lymph nodes, their presence is not strongly associated with other known factors of cervical cancer recurrence. Further research is needed to determine whether the presence of lymph node micrometastases is associated with an unfavorable prognosis.. II-3 Topics: Adult; Biomarkers; California; Carcinoma, Squamous Cell; Female; Hispanic or Latino; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Pelvis; Prognosis; Uterine Cervical Neoplasms | 2004 |
Possible association between HPV16 E7 protein level and cytokeratin 19.
The mechanisms employed by human papillomaviruses (HPVs) to control the replication of the viral genome and the expression of the viral genes are extremely complex and further complicated by the fact that the viral life cycle is intricately tied to the differentiation program of its host epithelial tissue. Indeed, HPV-induced immortalization of keratinocytes and disruption of the normal cytokeratin (CK) expression pattern progress pari passu during the stepwise process that preludes to squamous cell carcinoma. In our study, we have analyzed the interaction occurring between HPV type 16 E7 mRNA and the intermediate cytokeratin filaments 7 and 19 and report data in favor of a possible association between HPV16 E7 protein level and CK19. Topics: Carcinoma, Squamous Cell; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Keratin-7; Keratinocytes; Keratins; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus E7 Proteins; RNA, Messenger; Transcription Factors; Uterine Cervical Neoplasms; Zinc Fingers | 2004 |
Clinical evaluation of a new molecular method for detection of micrometastases in head and neck squamous cell carcinoma.
To better detect occult cervical metastases.. RNA from 153 cervical lymph nodes was analyzed for the presence of squamous cell carcinoma using quantitative cytokeratin (CK) 14 real-time reverse transcription polymerase chain reaction (RT-PCR). Detection of CK RNA in pathologically negative nodes was further analyzed by semi-step sectioning and CK immunohistochemistry. Subjects Thirteen consecutive patients with head and neck squamons cell carcinoma (HNSCC) presenting to the Department of Otolaryngology/Head and Neck Surgery of the University of North Carolina at Chapel Hill for neck dissection.. Cytokeratin detection was deemed nonspecific if expressed at fewer than 50 molecules of CK 14 RNA per nanogram total RNA. Of 35 HNSCCs, 33 expressed CK 14 RNA, and 15 lymph nodes with routine pathologically positive metastasis were also positive for CK 14 RNA. Four lymph nodes that were pathologically negative nodes were positive for CK 14 RT-PCR, with 2 containing metastases detected by semi-step sectioning.. Cytokeratin 14 RT-PCR is very sensitive for detecting micrometastasis in lymph nodes that are negative by routine pathological examination, with a relatively high false-positive rate. Quantitative CK 14 RT-PCR could be used to identify nodes negative for tumor by standard pathological analysis that should be examined by step sectioning and CK immunohistochemistry. Identification of micrometastases in patients with HNSCC will allow for appropriate and aggressive treatment of patients with metastatic disease. Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; False Positive Reactions; Female; Head and Neck Neoplasms; Humans; Keratins; Lymph Node Excision; Lymphatic Metastasis; Molecular Diagnostic Techniques; Neck Dissection; Neoplasm Staging; North Carolina; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Sensitivity and Specificity; Uterine Cervical Neoplasms; Women's Health | 2004 |
Evaluation of NMP179 for the detection of squamous intraepithelial neoplasia in ThinPrep cervical slides using a combination of double immunostaining and morphometric methods of analysis.
This study investigates the potential value of the nuclear matrix protein NMP179 as a marker of abnormal squamous cells in ThinPrep slides. Forty-six cervical scrapes were collected as cell suspensions and ThinPrep slides were prepared. They were double-immunostained for NMP179 and Cytokeratin 18 (CK18), an endocervical cell marker. The method of analysis adopted for the study was designed to distinguish the abnormal squamous cells from benign epithelial cell so that the percentages of abnormal squamous cells that expressed the marker could accurately be determined. Initially, an attempt was made to identify benign and abnormal cells in the ThinPrep slides on the basis of their morphology and immunostaining patterns. Discrimination between the various types of epithelial cells was incomplete using this approach and a more precise method of discrimination between the different epithelial cell types was carried out using a combination of double immunostaining (NMP179 and CK18) and morphometry using nuclear area and nuclear cytoplasmic ratios. Once the different epithelial cell types had been identified, the specificity and sensitivity of NMP179 were determined. The optimal sensitivity (89.9%) was achieved at the N/C ratio 0.36; however, the specificity of NMP179 was very low for all N/C ratios and ranged from 38.8% to 42.2%. Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Nuclear Matrix-Associated Proteins; Sensitivity and Specificity; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears | 2004 |
Combined signet ring cell and glassy cell carcinoma of the uterine cervix arising in a young Japanese woman: a case report with immunohistochemical and histochemical analyses.
Signet ring cell carcinoma and glassy cell carcinoma are both rare histological subtypes of uterine cervical cancer. This report is of a case of uterine cervical carcinoma arising in a 29-year-old woman who had major components of signet ring cell carcinoma and glassy cell carcinoma within the same tumor. Histochemical and immunohistochemical analyses, including high and low molecular weight cytokeratins, p63 and MUC5AC, additionally demonstrated the squamous and adenocarcinomatous differentiation in the neoplastic cells, which showed otherwise unclassifiable morphology on the haematoxylin-eosin sections. A wide range of differentiation described above supports the speculation that glassy cell carcinoma may arise from the multipotential immature cells that can differentiate into both squamous and glandular cells. It would be precise to classify this tumor as adenosquamous carcinoma. Although adenosquamous carcinoma is not a rare histological subtype in the uterine cervix, it should be necessary to report the presence of glassy cells and signet ring cells when present because the presence of both components is associated with an unfavorable clinical behavior. Topics: Adult; Biomarkers, Tumor; Carcinoma, Adenosquamous; Carcinoma, Signet Ring Cell; Chemotherapy, Adjuvant; DNA-Binding Proteins; Female; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Mucin 5AC; Mucins; Neoplasms, Multiple Primary; Phosphoproteins; Trans-Activators; Transcription Factors; Treatment Outcome; Tumor Suppressor Proteins; Uterine Cervical Neoplasms | 2004 |
Patterns of disease recurrence influenced by hematogenous tumor cell dissemination in patients with cervical carcinoma of the uterus.
The presence of isolated tumor cells (ITC) in the bone marrow at the time of primary diagnosis indicates an increased risk for subsequent development of distant metastases in various solid tumors. This study evaluates the prevalence and prognostic significance of ITC in patients with primary carcinoma of the cervix uteri.. We immunocytochemically analyzed bone marrow aspirates of 130 patients with newly diagnosed carcinoma of the cervix uteri for the presence of cytokeratin(CK)-positive cells from May 1994 to January 2001. We used a quantitative immunoassay with the monoclonal anti-CK antibody A45-B/B3 and evaluated 2 x 10(6) bone marrow cells per patient. Patients were followed prospectively for a median of 43 (range, 1-85) months.. Isolated tumor cells were found in the bone marrow of 38 patients (29%). The presence of ITC did not correlate with the International Federation of Gynecology and Obstetrics (FIGO) tumor stage (P = 0.61), pelvic and paraaortal lymph node involvement (P = 0.41), histopathologic grading (P = 0.67), the histologic type of the carcinoma (P = 0.93), invasion of lymph nodes (P = 0.93) and blood vessels (P = 0.92), or with menopausal status (P = 0.17). The bone marrow status at the time of primary diagnosis did not correlate with the overall survival as estimated by Kaplan-Meier analysis (P = 0.30). However, distant metastases occurred in 5% of the patients (n = 5) with negative bone marrow status and in 15% of the patients (n = 6) with positive bone marrow status (P = 0.054). The median distant disease-free survival period was 78 months (95% confidence interval 73-82) in patients with negative bone marrow status and 72 months (95% CI 61-82) in patients with positive bone marrow status (P = 0.051). Multivariate analysis revealed the presence of ITC as a significant, independent risk factor for the subsequent development of distant metastases (relative risk 3.6, P = 0.046).. Despite the locoregional predominance of cervical carcinoma at the time of primary diagnosis, the presence of ITC in the bone marrow indicates an increased risk for the development of distant metastases. This information may prove useful to stratify patients for systemic treatment. Topics: Adult; Bone Marrow Neoplasms; Carcinoma; Combined Modality Therapy; Female; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Prognosis; Proportional Hazards Models; Risk Factors; Survival Analysis; Uterine Cervical Neoplasms | 2003 |
Cervical polyp with eccrine syringofibroadenoma-like features.
Topics: Adenoma, Sweat Gland; Biomarkers, Tumor; Eccrine Glands; Female; Fibroadenoma; Humans; Keratins; Middle Aged; Polyps; Sweat Gland Neoplasms; Treatment Outcome; Uterine Cervical Neoplasms | 2003 |
Immunoprofile of cervical and endometrial adenocarcinomas using a tissue microarray.
Adenocarcinomas of the uterine cervix show a wide range of morphological features, and can be confused with endometrial adenocarcinoma in biopsy or curetting specimens. The objective of this study was to use tissue microarray technology to evaluate the immunoprofile of a large set of uterine adenocarcinomas with an extended panel of antibodies, comparing the profile of primary cervical and endometrial adenocarcinomas. A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 141 hysterectomy specimens. Duplicate 0.6-mm cores were obtained from 57 cervical adenocarcinomas (16 in situ and 41 invasive) and 84 endometrial adenocarcinomas. Tissue array sections were immunostained with 21 commercially available antibodies [B72.3, CD 99, carcinoembryonic antigen (CEA), c-kit, pancytokeratin, CK 5/6, CK 7, CK8/18, CK19, CK 20, CK 22, EMA, estrogen receptor (ER), KP-1, melan-A, p53, PLAP, S-100, synaptophysin, TTF-1, and vimentin] utilizing the avidin-biotin (ABC) technique. Hierarchical clustering analysis of the tumors was done based on the immunostaining results. Only ER ( P<0.001), CEA ( P=0.04), vimentin ( P<0.001), and CK 8/18 ( P=0.002) showed a significantly different frequency of positivity in endometrial relative to cervical adenocarcinomas. ER, vimentin, and CK 8/18 were more likely to be expressed in endometrial adenocarcinomas, while cervical adenocarcinomas more frequently expressed CEA. We were able to identify immunoprofiles that were highly specific for endocervical adenocarcinoma (ER(-), vimentin(-), CK 8/18(-), CEA(+)) or endometrial adenocarcinoma (ER(+), vimentin(+), CK 8/18(+), CEA(-)), but most tumors showed an intermediate, non-specific immunophenotype. Hierarchical clustering analysis was useful in the interpretation of these intermediate immunophenotypes. Papillary serous adenocarcinoma of the endometrium was less likely to express vimentin ( P=0.002) than endometrioid carcinoma of the endometrium. Topics: Adenocarcinoma; Carcinoembryonic Antigen; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Receptors, Estrogen; Uterine Cervical Neoplasms; Vimentin | 2003 |
Mixed papillary transitional cell carcinoma and adenocarcinoma of the uterine cervix: a clinicopathologic study of three cases.
Although tumors consisting of a combination of transitional cell carcinoma (TCC) and adenocarcinoma have been described in the endometrium, they have not been documented in the uterine cervix to our knowledge. Three such cervical cases are reported in this article. Three patients, whose ages ranged from 40 to 61 years, presented with vaginal bleeding and malignant cells on routine Papanicolaou smears. The initial diagnoses based on a biopsy specimen were poorly differentiated squamous cell carcinoma in two patients and adenocarcinoma with a solid component in the third patient. All patients underwent radical hysterectomy. The hysterectomy specimens each contained a polypoid endocervical mass with minimal invasion of the cervical stroma. On microscopic examination, each tumor consisted of a component of papillary TCC admixed with an adenocarcinoma of endometrioid type. Both carcinomatous components were immunoreactive for cytokeratin (CK) 7 but not CK20. The three patients were alive and disease-free from 10 months to 4 years postoperatively. Recognition of this unusual variant of cervical carcinoma is important to delineate its clinical and pathologic features and establish prognostic differences, if any, from other histologic subtypes of cervical carcinoma. Papillary TCC mixed with adenocarcinoma broadens the morphologic spectrum of transitional cell neoplasms of the uterine cervix. Topics: Adenocarcinoma; Adult; Carcinoma, Transitional Cell; Female; Humans; Hysterectomy; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; Neoplasms, Multiple Primary; Papanicolaou Test; Uterine Cervical Neoplasms; Uterine Hemorrhage; Vaginal Smears | 2003 |
Uterine tumor resembling ovarian sex-cord tumor: report of a case mimicking cervical adenocarcinoma.
Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are unusual neoplasms with histologic features that resemble those within ovarian Sertoli and granulosa cell tumors. We report the case of a 24-year-old woman with a UTROSCT presenting as a cervical mass, which on initial evaluation was thought to represent cervical adenocarcinoma. The patient's cervical biopsy specimen contained epithelioid cells arranged in tubules and anastomosing cords, without significant cellular atypia or mitotic activity. Because this morphology elicited a broad differential diagnosis, immunohistochemical studies were performed. The tumor was found to be diffusely positive for cytokeratin cocktail, calretinin, and desmin, focally positive for CK7 and SMA, and negative for EMA, CEA, inhibin, CD10, CK20, chromogranin, and synaptophysin. Ultrastructural examination revealed occasional gland-like lumens with cells joined by desmosomes and a continuous basal lamina. UTROSCTs have features that may cause them to be confused with more common tumors, especially in limited biopsy samples, and should be included in the differential diagnosis when a gland-forming neoplasm with an unusual appearance is identified in a cervical or endometrial biopsy specimen. Topics: Actins; Adenocarcinoma; Adult; Biopsy; Calbindin 2; Cell Nucleus; Cytoplasm; Desmin; Diagnosis, Differential; Female; Humans; Hysterectomy; Immunohistochemistry; Keratin-7; Keratins; Microscopy, Electron; Muscle, Smooth; Ovarian Neoplasms; S100 Calcium Binding Protein G; Sex Cord-Gonadal Stromal Tumors; Uterine Cervical Neoplasms; Uterine Neoplasms | 2003 |
Primary cervical adenocarcinoma with intestinal differentiation and colonic carcinoma metastatic to cervix: an investigation using Cdx-2 and a limited immunohistochemical panel.
Cdx-2 is expressed in normal colonic epithelia and in most colorectal adenocarcinomas. No data exist on Cdx-2 expression in primary cervical adenocarcinoma with colonic differentiation.. To ascertain the utility of Cdx-2 and a limited immunohistochemical panel in differentiating between primary cervical adenocarcinoma with intestinal differentiation and secondary (colonic) cervical adenocarcinoma, which call for different surgical and chemotherapeutic treatment protocols.. We examined cervical tract adenocarcinomas in women with previously negative medical histories for neoplastic disease and in women with colonic carcinoma. An immunohistochemical panel consisting of cytokeratin 7, cytokeratin 20, carcinoembryonic antigen, and a new marker, Cdx-2, was evaluated in all cases. The clinical data, the morphologic features, and the immunohistochemical staining patterns were compared.. Of the tumors diagnosed as metastatic intestinal adenocarcinoma of the cervix, based on clinical data and hematoxylin-eosin-stained sections, all were Cdx-2 positive, whereas Cdx-2 was not expressed in any of our cases of primary cervical adenocarcinoma with colonic differentiation. Carcinoembryonic antigen was expressed both in primary cervical tumor and in secondary (intestinal) cervical adenocarcinoma. Cytokeratin 20 was not expressed in our cases of cervical adenocarcinoma, and it was not expressed in 7.15% of cervical metastases from intestinal carcinoma. Immunostaining with cytokeratin 7 was positive in cervical adenocarcinoma, but was negative in secondary (intestinal) cervical adenocarcinoma.. Our immunohistochemical analysis shows that Cdx-2 has good specificity and would be a good marker to use in a limited panel of immunohistochemical markers, such as cytokeratin 7, cytokeratin 20, and carcinoembryonic antigen, to distinguish primary cervical adenocarcinoma from intestinal metastases to the cervix. Topics: Adenocarcinoma; Carcinoembryonic Antigen; Carcinoma; CDX2 Transcription Factor; Cell Differentiation; Colon; Colonic Neoplasms; Diagnosis, Differential; Female; Homeodomain Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Trans-Activators; Uterine Cervical Neoplasms | 2003 |
Prognostic significance of intratumour microvessel density and haemoglobin level in carcinoma of the uterine cervix.
The prognostic significance of intratumour microvessel density (IMD) and haemoglobin (Hb) level was studied in 152 (FIGO stage IB-IIIB) cervical cancer patients before radiotherapy. Patients' age and tumour stage, grade and degree of keratinization were also studied. IMD measurement expressed as the mean vessel count per 1 mm2 was performed on formalin-fixed, paraffin-embedded tumour biopsies stained with anti-factor VIII antibody (DAKO Ltd.) using immunohistochemistry and the vascular hot-spot technique. The median age of patients was 55 years (29-80). Median values for IMD and Hb level were: 142.5 (range 56.3-476.6) vessels/mm2 and 129 (range 81-160) gil, respectively. The median time of follow-up was 26 months, with a range of 2-145 months. Tumour stage (p = 0.7009), grade (p = 0.6660) and degree of keratinization (0.2669) were not significant in the Kaplan-Meier univariate analysis. However, patients' age > 50 years (p = 0.0079). high vascularity (IMD > 190.0 vessels/mm2, minimal cut-off point, p = 0.0503) and Hb concentration > 116 g/l (p = 0.0213) were favourable prognostic factors for cervical cancer treated with radiotherapy. In the Cox multivariate analysis only higher vascularity (IMD > 190/mm2 and Hb concentration > 116 g/l were favourable prognostic factors in terms of patients' survival. However, when a Cox analysis was done separately for keratinizing and non-keratinizing tumours, it was found that higher vascularity was significant only for keratinizing, and higher Hb level only for non-keratinizing cancers. Topics: Adult; Aged; Aged, 80 and over; Anemia; Capillaries; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Hemoglobins; Humans; Keratins; Life Tables; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Neovascularization, Pathologic; Prognosis; Proportional Hazards Models; Survival Analysis; Treatment Outcome; Uterine Cervical Neoplasms | 2002 |
Small cell carcinoma of the cervix: a clinicopathologic and immunohistochemical study of 23 cases.
Twenty-three patients with primary small cell carcinoma of the uterine cervix are presented. Their ages ranged between 23 and 63 years (average, 43 years). Blood spotting or vaginal bleeding was the most common clinical presentation. Histologically, the tumors were densely cellular and showed trabecular nesting or a sheet-like pattern. The neoplastic cells had scant cytoplasm, round nuclei, absence of nucleoli, and finely dispersed chromatin. Nuclear molding, single cell necrosis, and high mitotic activity were found in all tumors. There was a minor component of large cell neuroendocrine carcinoma in three cases, while foci of adenocarcinoma were identified in two cases. Immunohistochemical studies were performed in all 23 tumors which showed immunoreactivity for cytokeratin. Ten small cell carcinomas were immunoreactive for chromogranin, 13 for synaptophysin, and 10 expressed p53 protein. Treatment modalities included hysterectomy alone or combined with chemotherapy and/or radiation therapy. A few patients received chemotherapy and/or radiation alone. Follow-up information was obtained in 22 cases; 15 patients died of tumor between 6 and 43 months, while seven patients have remained alive 12 to 273 months. One patient was lost to follow-up. Small cell carcinoma of the cervix is a highly aggressive neoplasm. However, early diagnosis and combined therapeutic modalities may lead to longer survival in some patients. Although the use of immunohistochemistry may be helpful in the diagnosis, small cell carcinoma still remains a morphologic diagnosis. Topics: Adenocarcinoma; Adult; Biomarkers; Carcinoma, Small Cell; Chromogranins; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Middle Aged; Synaptophysin; Treatment Outcome; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms | 2002 |
Evaluation of prognostic factors following flow-cytometric DNA analysis after cytokeratin labelling: II. Cervical and endometrial cancer.
In gynecologic oncology valid prognostic factors are necessary to define biologically similar subgroups for analysis of therapeutic efficacy. This study is the first published prospective study concerning prognostic significance of DNA ploidy and S-phase fraction in cervical and endometrial cancer following enrichment of tumor cells by cytokeratin labelling. Epithelial cells were labeled by FITC-conjugated cytokeratin antibody (CK 5, 6, 8, and CK 17) prior to flow cytometric cell cycle analysis in 91 specimens of cervical cancer and 73 samples of endometrial cancer. In cervical cancer neither DNA-ploidy nor S-phase fraction were relevant prognostic parameters. But CV of the G(0)G(1)-peak showed prognostic relevance in cervical cancer cells, even in multivariate analysis. This interesting observation, however, seems to have no therapeutic consequence due to the small discrimination capacity of CV. In endometrial carcinoma, gross DNA-aneuploidy (DNA-index > 1.3) and a high percentage of proliferating cells (>75th percentile) were univariate and multivariate highly significant prognostic factors for recurrence-free survival. Especially DNA-aneuploidy (DI>1.3) is one of the most important independent molecular biological prognostic factors. While diagnostic curettage we could identify risk patients even preoperatively by determination of the prognostic factors like histologic tumor type, grading, cervical involvement and DNA-ploidy. Thereby these patients could be treated primarily in an oncologic center. In conclusion, our investigations showed that the determination of DNA-ploidy should be done in endometrial carcinoma. In cervical cancer no clinical significance for determination of DNA-parameters was found. Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; DNA, Neoplasm; Endometrial Neoplasms; Evaluation Studies as Topic; Female; Flow Cytometry; G1 Phase; G2 Phase; Humans; Keratins; Middle Aged; Mitosis; Multivariate Analysis; Neoplasm Recurrence, Local; Ploidies; Predictive Value of Tests; Prognosis; Resting Phase, Cell Cycle; S Phase; Survival Analysis; Uterine Cervical Neoplasms | 2002 |
Serum squamous cell carcinoma antigen and CYFRA 21-1 in cervical cancer treatment.
To analyze whether serum squamous cell carcinoma (SCC) antigen and cytokeratin-19 fragments (CYFRA) levels can assist in selecting patients with locally advanced cervical cancer who will benefit from combined treatment or additive surgery.. Of 114 patients with cervical cancer Stage IB-IV, the first 39 patients received radiotherapy, the following 75 patients received identical radiotherapy plus concomitant chemotherapy (3 cycles of carboplatin and 5-fluorouracil). SCC antigen and CYFRA 21-1 serum levels were measured before treatment, after therapy, and during follow-up. Baseline tumor markers were related to tumor stage and size and clinical outcome.. Before treatment, SCC antigen was elevated (>1.9 microg/L) in 60% and CYFRA 21-1 (>2.2 microg/L) in 46% of patients. For all patients, disease-free survival (DFS) was better after combined treatment (67% vs. 43%, p < 0.0005). For patients with elevated baseline SCC antigen, DFS was better after combination therapy (67% vs. 27%, p = 0.001) which resulted more frequently in a normal SCC antigen (93% vs. 65%, p = 0.004). In contrast, in those with a normal baseline CYFRA 21-1, combined therapy resulted in a better DFS (p = 0.04). Patients who achieved a normal SCC antigen or CYFRA 21-1 after treatment had a better DFS (respectively 63 vs. 17% and 64 vs. 30%). Elevated SCC antigen posttreatment indicated residual tumor in 11/12 patients (92%), elevated CYFRA 21-1 in 7/10 patients (70%). Forty-seven patients had a tumor recurrence. At recurrence, SCC antigen was raised in 70% and CYFRA 21-1 in 69%.. In patients with an elevated pretreatment SCC antigen, SCC antigen normalized more frequently with combined treatment and those patients had a better DFS. Elevated SCC antigen or CYFRA 21-1 levels after treatment completion indicated residual tumor in respectively 92% and 70%. The presence of elevated posttreatment levels of SCC antigen or CYFRA 21-1 indicates the need for additional salvage surgery. SCC antigen proved to be superior to CYFRA 21-1 in predicting DFS and disease recurrence. Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Combined Modality Therapy; Female; Humans; Keratin-19; Keratins; Middle Aged; Neoplasm Staging; Serpins; Uterine Cervical Neoplasms | 2002 |
A panel of immunohistochemical stains, including carcinoembryonic antigen, vimentin, and estrogen receptor, aids the distinction between primary endometrial and endocervical adenocarcinomas.
The histological distinction between a primary endometrial and a primary endocervical adenocarcinoma is often difficult, especially in small biopsy specimens. A preoperative distinction is important because primary surgical management differs between the two tumors. Cases of primary endometrioid endometrial (n=30) and primary endocervical (n=26) adenocarcinoma of endocervical type were stained immunohistochemically with the monoclonal antibodies against carcinoembryonic antigen (CEA), vimentin, estrogen receptor (ER), and 34 beta E12. In all cases the origin of the adenocarcinoma was confirmed by examination of the definitive pathology specimen. There was diffuse positive nuclear staining for ER in 28 of 30 (93%) endometrial adenocarcinomas. ER was negative in 16 of 26 endocervical adenocarcinomas, and there was focal weak nuclear staining in the other cases. Vimentin was positive in 29 of 30 (97%) endometrial adenocarcinomas but in only 2 of 26 (8%) endocervical adenocarcinomas. CEA was positive in 25 of 26 (96%) endocervical adenocarcinomas, mostly with diffuse membranous and cytoplasmic staining. Positivity with CEA was present in 21 of 30 (70%) endometrial adenocarcinomas but was largely confined to squamoid areas with only 12 tumors exhibiting focal membranous staining of the glandular component. 34 beta E12 was diffusely positive in all except one cervical adenocarcinoma. In endometrial carcinomas, positivity was strongest in squamoid areas but there was positive staining, either focally or diffusely, of the glandular component in 27 cases. In summary, primary endometrioid endometrial adenocarcinomas are characterized by diffuse, strong, positive staining for vimentin and ER and negative or very focal, positive staining of the glandular component for CEA. In contrast, primary endocervical adenocarcinomas are characterized by CEA positivity, which is usually but not always diffuse, negativity for vimentin, and negativity or focal weak positivity for ER. 34 beta E12 is of no value in the distinction between endometrial and endocervical adenocarcinomas. A panel of immunohistochemical stains, comprising CEA, vimentin, and ER, generally allows confident preoperative distinction between a primary endometrial and endocervical adenocarcinoma. Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Receptors, Estrogen; Uterine Cervical Neoplasms; Vimentin | 2002 |
Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study.
We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction. Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Mucin-1; Uterine Cervical Neoplasms; Vimentin | 2002 |
Glassy cell carcinoma of the uterine cervix: histochemical, immunohistochemical, and molecular genetic observations.
Glassy cell carcinoma (GCC) of the uterine cervix is characterized by distinctive cytological features and an aggressive clinical course. Although this tumor has been usually considered a poorly differentiated variety of adenosquamous carcinoma (ASC), a clarification of the phenotype and histogenesis of GCC is still required. We examined three GCCs and four ASCs for histochemical and immunohistochemical phenotypes and molecular genetic status, comparing them with five nonkeratinizing squamous cell carcinomas and five endocervical-type mucinous adenocarcinomas. GCCs had a profile of cytokeratin expression similar to that of reserve cells or immature squamous cells of the cervix. In addition to squamous differentiation, GCCs sporadically produced intestinal-type mucin. HPV 18 was detected in two of three GCCs and two of four ASCs. GCCs may originate from multipotential stem or reserve cells that undergo early squamous differentiation. The presence of HPV 18 might stimulate biphasic squamous and glandular differentiation. Topics: Adenocarcinoma, Mucinous; Carcinoma, Adenosquamous; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Microsatellite Repeats; Molecular Biology; Mucin-1; Mucin-2; Mucins; Oncogene Proteins, Viral; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Uterine Cervical Neoplasms | 2002 |
Detecting cytokeratin 19 mRNA in the peripheral blood cells of cervical cancer patients and its clinical-pathological correlation.
The aim of this study was to study the presence of cytokeratin 19 (CK19)-expressing cancer cells in the blood of preoperative patients with FIGO stage Ib and IIb cervical cancers who received radical hysterectomy and to investigate the cells' clinical significance.. CK19 mRNA in the blood cells of the patients was detected preoperatively by a newly designed nested reverse transcriptase-polymerase chain reaction, which excluded pseudogenes a and b, performed on 84 patients with stage Ib and IIb cervical carcinoma. Possible correlations between clinicopathological factors were then analyzed.. The sensitivity of this assay was 1 CK19-mRNA-positive cell per 10(6) peripheral blood mononuclear cells. Results showed that 21.4% of the 84 patients with cervical carcinoma had CK19-mRNA-positive cells in the blood, in comparison with 5.7% of the 35 patients with benign gynecological tumors and 0% of the 28 healthy controls (P = 0.037 and 0.006, respectively). The positive tests in the cervical cancer patients were not associated with prognostic factors including stage, pelvic lymph node metastasis, pathological types, bulky tumor size (> or =4 cm), differentiation, parametrial extension, lymphovascular space involvement, deep stromal invasion, or age.. This study revealed the presence of circulating CK19-expressing cancer cells in the blood of patients with untreated early-stage cervical carcinomas, indicating that cervical cancer disseminated early. The survival effect of this phenomenon must be clarified. This detection assay provides an early checkpoint in the multistep process for developing metastasis in cervical cancer patients. Topics: Adult; Female; Humans; Keratins; Middle Aged; Neoplastic Cells, Circulating; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity; Uterine Cervical Neoplasms | 2002 |
Highly differentiated keratinizing squamous cell cancer of the cervix.
Topics: Adenocarcinoma; Carcinoma, Squamous Cell; DNA, Neoplasm; DNA, Viral; Female; Humans; In Situ Hybridization; Keratins; Papillomaviridae; Papillomavirus Infections; Polymerase Chain Reaction; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 2002 |
Immunohistochemical staining in the distinction between primary endometrial and endocervical adenocarcinomas: another viewpoint.
Several studies have reported on the use of antibodies to monoclonal carcinoembryonic antigen (CEA) and vimentin (VIM) to distinguish between adenocarcinomas of endometrial (EM) and endocervical (EC) origin, with variably enthusiastic results. It is still unclear whether site of origin or pathway of differentiation (endometrioid [em] versus mucinous [m]) is more important in predicting immunohistochemical differences. In the present study, paraffin blocks from adenocarcinomas of known origin were retrieved and immunostained with monoclonal antibodies to VIM and CEA, as well as cytokeratins (CK) 4, 18, and 20, estrogen receptor (ER), and progesterone receptor (PR). Positivity was scored on a scale from 0 to 12, with emphasis on the pattern of differentiation (tumors with mixed patterns received separate scores for the em and m foci). Mean CEA scores for emEM (n = 27), mEM (17), mEC (10), and emEC (6) were 0.4, 0.9, 5.1, and 1.2, respectively. VIM scores were 6.9, 1.3, 0, 4.4; ER, 5.7, 4.2, 0, 1.6; PR, 7.6, 2.8, 0.1, 6.0; CK4, 9.2, 4.4, 8.5, 10.6; CK18, 6.4, 3.4, 5.5, 8.4; CK20, 0.7, 0, 0.5, 0.4. Both site and differentiation influenced these results, with the latter more important for VIM and PR, the former for ER, both for CEA (only mEC was frequently strongly positive), and neither for the CKs studied. No one stain or combination reliably distinguished endometrial from endocervical origin. The only immunostaining pattern that might identify a site of origin with more accuracy than hematoxylin & eosin evaluation alone is the combination of high VIM and ER scores in an endometrioid carcinoma, suggesting with about 95% accuracy in this series an endometrial origin of the tumor. Topics: Adenocarcinoma, Mucinous; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Ovarian Neoplasms; Receptors, Estrogen; Receptors, Progesterone; Uterine Cervical Neoplasms; Vimentin | 2002 |
Radioimmunodetection of cervical carcinoma xenografts with (111)In-labeled MAb Cx-99 detected by a hand-held gamma detector.
To establish a radioimmunodetection (RAID) system for localization of cervical cancer by labeling 111-indium ((111)In) to a monoclonal antibody against cytokeratin 19 (MAb Cx-99), and detecting it with a hand-held gamma detector in an animal model.. MAb Cx-99 was labeled with 111-Indium by the DTPA chelating method. From the second day to the seventh day after injection of this immunoconjugate into athymic nude mice bearing cervical cancer cell line CC7T xenografts, the biodistribution ratios of tumor and non-tumor radioactivity were detected by a hand-held gamma detector. Data were also correlated with the data detected by the conventional gamma counter.. The labeling efficiency of this (111)In-labeled MAb Cx-99 and (111)In-labeled MOPC was 91.6% and 95.5%, respectively. After injection, the liver, kidney and lung were initially noticed to have high radioactivity, but the localization of tumor/tissue ratios increased progressively as time passed, indicating the effect of delayed detection for distinguishing tumor from non-tumor tissues. Except for the spleen, the range of tumor/tissue ratios was 1.18-32.7 and 1.14-39.35 for the fourth day and the seventh day, respectively. The tumor/spleen ratio remained low until the seventh day after injection, thus indicating that the spleen might have a different excretion rate.. This study indicated the feasibility of a hand-held detection system in the localization of cervical cancer after injection of (111)In-labeled MAb Cx-99. The effect of delayed detection was obvious by the decreasing high bindings in the liver, spleen and kidney, with the applicable detection time being four to seven days after injection. Topics: Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Female; Humans; Indium Radioisotopes; Keratins; Mice; Mice, Inbred BALB C; Mice, Nude; Predictive Value of Tests; Radioimmunodetection; Sensitivity and Specificity; Transplantation, Heterologous; Tumor Cells, Cultured; Uterine Cervical Neoplasms | 2002 |
Expression of the p53 homologue p63 in early cervical neoplasia.
p63, a homologue of the tumor suppressor gene p53, is expressed in embryonic, adult murine, and human basal squamous epithelium and encodes both transactivating and dominant negative transcript isoforms. Mouse embryos functionally deficient in p63 fail to replenish basal squamous epithelial cells, resulting in multiple defects that include absent genital squamous epithelium. This study investigated the expression of p63 in the human cervical transformation zone and early cervical neoplasia.. Tissue localization of p63 was determined by immunohistochemistry in a wide range of epithelia. A correlation was also made between p63 expression and squamous basal cell (keratin 14), endocervical columnar cell (mucicarmine), and cell-cycle specific (Ki-67) markers.. p63 expression by immunostaining delineated basal and parabasal cells of maturing ectocervical squamous mucosa, squamous metaplasia in the cervix, and basal and subcolumnar cells of the cervical transformation zone. In atrophic epithelia immunostaining for p63 was present in all cell strata. In early cervical neoplasia, p63 expression was inversely correlated with both squamous cell maturation and nonsquamous differentiation in CIN. This biomarker also identified basal cells in a subset of preinvasive cervical neoplasms with endocervical cell differentiation that were bcl-2 and keratin 14 negative.. In the lower female genital tract, p63 is preferentially expressed in immature cells of squamous lineage and is not linked to cell proliferation. The broader range of p63 expression relevant to keratin 14 and bcl-2 indicates that p63 may identify additional subsets of benign and neoplastic epithelial basal cells in the cervical transformation zone and may be useful in studying cell differentiation in the early stages of neoplastic change in this region. Topics: Adenocarcinoma; Atrophy; Biomarkers, Tumor; Carcinoma in Situ; Cell Cycle; Cell Differentiation; Cervix Uteri; DNA-Binding Proteins; Epithelium; Female; Gene Expression; Genes, Tumor Suppressor; Humans; Keratin-14; Keratins; Ki-67 Antigen; Membrane Proteins; Phosphoproteins; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 2001 |
Molecular quantification and mapping of lymph-node micrometastases in cervical cancer.
A proportion of patients with cancer and lymph nodes negative on histology will develop recurrence. Reverse-transcriptase PCR (RT-PCR) is a highly sensitive method for detection of lymph-node micrometastases, but accurate quantitative assessment has been difficult.. We studied primary tumours and 156 lymph nodes from 32 patients with cervical cancer (stage IA2, IB1, and IB2) and 32 lymph nodes from nine patients with benign disease. A fully quantitative, real-time RT-PCR assay was used to document absolute copy numbers of the epithelial marker cytokeratin 19. Primers and probe were designed not to amplify either of the two cytokeratin 19 pseudogenes.. All primary tumours and histologically involved lymph nodes (six) had more than 106 copies of cytokeratin 19 mRNA per microg total RNA. Expression of cytokeratin 19 (up to 1.1 x 10(5) copies per microg RNA) was detected in 66 (44%) of 150 histologically uninvolved lymph nodes, and in nodes from 16 of 32 patients with cervical cancer. 15 of these 16 patients with evidence of micrometastases had the highest cytokeratin 19 transcription level in a first lymph-node drainage station (three obturator, six internal, and six external iliac node). Transcription of cytokeratin 19 was found at a low level in just one of 32 lymph nodes obtained from nine patients with benign disease. Median copy number of cytokeratin 19 transcription was significantly higher (>10(3) copies) in association with adverse prognostic features.. The results suggest that about 50% of early-stage cervical cancers shed tumour cells to the pelvic lymph nodes. The amount of cytokeratin 19 expression was related to clinicopathological features. Further studies are required to document the clinical implications of molecular micrometastases. Topics: Adult; Aged; Base Sequence; Female; Follow-Up Studies; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Molecular Sequence Data; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transcription, Genetic; Uterine Cervical Neoplasms | 2001 |
Nonspecific down-regulation of CD8+ T-cell responses in mice expressing human papillomavirus type 16 E7 oncoprotein from the keratin-14 promoter.
The E7 oncoprotein of human papillomavirus 16 (HPV16) transforms basal and suprabasal cervical epithelial cells and is a tumor-specific antigen in cervical carcinoma, to which immunotherapeutic strategies aimed at cytotoxic T-lymphocyte (CTL) induction are currently directed. By quantifying major histocompatibility complex class I tetramer-binding T cells and CTL in mice expressing an HPV16 E7 transgene from the keratin-14 (K14) promoter in basal and suprabasal keratinocytes and in thymic cortical epithelium, we show that antigen responsiveness of both E7- and non-E7-specific CD8+ cells is down-regulated compared to non-E7 transgenic control mice. We show that the effect is specific for E7, and not another transgene, expressed from the K14 promoter. Down-regulation did not involve deletion of CD8+ T cells of high affinity or high avidity, and T-cell receptor (TCR) Vbeta-chain usage and TCR receptor density were similar in antigen-responsive cells from E7 transgenic and non-E7 transgenic mice. These data indicate that E7 expressed chronically from the K14 promoter nonspecifically down-regulates CD8+ T-cell responses. The in vitro data correlated with the failure of immunized E7 transgenic mice to control the growth of an E7-expressing tumor challenge. We have previously shown that E7-directed CTL down-regulation correlates with E7 expression in peripheral but not thymic epithelium (T. Doan et al., J. Virol. 73:6166-6170, 1999). The findings have implications for the immunological consequences of E7-expressing tumor development and E7-directed immunization strategies. Generically, the findings illustrate a T-cell immunomodulatory function for a virally encoded human oncoprotein. Topics: Animals; CD8-Positive T-Lymphocytes; Down-Regulation; Female; Humans; Immunization; Immunologic Memory; Keratin-14; Keratins; Mice; Oncogene Proteins, Viral; Papillomavirus E7 Proteins; Promoter Regions, Genetic; Receptors, Antigen, T-Cell; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocytes, Cytotoxic; Uterine Cervical Neoplasms | 2001 |
Lobular endocervical glandular hyperplasia is a metaplastic process with a pyloric gland phenotype.
Lobular endocervical glandular hyperplasia of the uterine cervix is a rare pseudoneoplastic lesion of the uterine cervix, described recently. Our aim was to characterize the clinicopathological and immunohistochemical features of lobular endocervical glandular hyperplasia, to elucidate its pyloric gland phenotype, and to distinguish it from adenoma malignum of the uterine cervix.. Nine cases of lobular endocervical glandular hyperplasia were studied histologically and immunohistochemically. The average age of the nine patients was 48.8 years (range 38-64 years). Six cases were found incidentally, whereas in three cases a watery vaginal discharge and imaging studies suggested adenoma malignum preoperatively. Microscopically, lobular endocervical glandular hyperplasia ranged from 1 mm to 20 mm (mean 6.8 mm) in the largest horizontal extent and 1 mm to 10 mm (mean 3.9 mm) in depth, and was characterized by lobular arrangements of small glands composed of low columnar cells with pale eosinophilic cytoplasm and bland nuclei. Three cases showed a pseudo-invasive growth. Intracytoplasmic mucin was predominantly PAS-positive, and seven cases showed immunoreactivity for M-GGMC-1, an antibody that reacts with pyloric gland-type mucin. Only focal and faint reactivity for CEA was seen, and ER was negative in all cases. The cytokeratin profile was CK7+/20- in all cases, in keeping with their Müllerian derivation. All three lesions examined contained chromogranin-positive endocrine cells. After surgery all patients are well without recurrent disease (mean follow-up was 48.4 months).. Lobular endocervical glandular hyperplasia is a morphologically distinct pseudoneoplastic glandular lesion, which has unique phenotypic characteristics shared by pyloric glands of the stomach. Although most are found incidentally, some cases may show clinical and radiological features resembling those of adenoma malignum. Topics: Adenocarcinoma, Mucinous; Adult; Carcinoembryonic Antigen; Cervix Uteri; Chromogranin A; Chromogranins; Diagnosis, Differential; Female; Gastric Mucosa; Humans; Hyperplasia; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Metaplasia; Middle Aged; Mucins; Receptors, Estrogen; Uterine Cervical Neoplasms | 2001 |
Highly differentiated keratinizing squamous cell cancer of the cervix: a rare, locally aggressive tumor not associated with human papillomavirus or squamous intraepithelial lesions.
The purpose of this study is to report an unusual variant of cervical squamous cell carcinoma, not associated with either human papillomavirus infection or antecedent squamous intraepithelial lesions. Five women had a diagnosis of invasive cervical cancer discovered at hysterectomy performed for prolapse (two cases), leiomyoma (one case), or a vaginal fistula (two cases). The women ranged in age from 47 to 78 years (mean 59 years). Four of the five had a history of normal Papanicolaou (Pap) smears; the other had a Pap smear diagnosis of atypical squamous cells of undetermined significance (ASCUS). All had large cervical tumors (two with parametrial involvement and one with vaginal involvement) that showed extensive keratin formation, an inverted pattern of growth, and, except for one case, minimal cytologic atypia. There was extensive hyperkeratosis and parakeratosis adjacent to each tumor; none had evidence of squamous intraepithelial lesion. Human papillomavirus testing by polymerase chain reaction in situ hybridization and reverse-transcribed polymerase chain reaction in situ was negative in each case, compared with a detection rate of 107 of 108 (99%) for squamous intraepithelial lesion-associated cervical squamous cell and adenocarcinomas. Two of the women died of extensive local recurrence; two other women were recently diagnosed. We conclude that highly differentiated keratinizing squamous cell carcinoma of the cervix is a rare entity not associated with human papillomavirus infection or squamous intraepithelial lesion and thus difficult to detect on routine cervical cancer screening. Topics: Adult; Aged; Carcinoma, Squamous Cell; DNA, Neoplasm; DNA, Viral; Female; Humans; In Situ Hybridization; Keratins; Middle Aged; Papillomaviridae; Papillomavirus Infections; Reverse Transcriptase Polymerase Chain Reaction; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 2001 |
Ectopic prostatic tissue in the uterine cerrix.
Topics: Adult; Choristoma; Female; Humans; Keratins; Male; Molecular Weight; Prostate; Prostate-Specific Antigen; Uterine Cervical Diseases; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 2001 |
Loss of cytokeratin 14 expression is related to human papillomavirus type and lesion grade in squamous intraepithelial lesions of the cervix.
In a recent study of low-grade cervical squamous intraepithelial lesions (SILs), we reported that infection with both low- and high-risk human papillomaviruses (HPVs) upregulated cyclin A, B, E, and Ki67 expression in basal and suprabasal cells. In view of the intricate link between cell cycle exit, proliferation, and differentiation, we examined the morphologic distribution of cytokeratins 13 and 14 and involucrin expression in 49 low-grade SILs infected with HPV types 6, 11, 16, 18, 31, 33, 39, 42, 43, 44, 45, 51, 52, 56, 58, and 66; 2 lesions contained both low- and high-risk HPVs. The findings were compared with 30 high-grade SILs infected with HPV types 16, 31, 33, 51, 58, 66, and 67; 3 of these were infected with 2 different HPVs. In low-grade lesions, the differentiation markers were expressed normally, showing that differentiation proceeds despite upregulation of cell cycle--associated proteins. Loss of involucrin (3 of 33) and cytokeratin 13 (8 of 33) expression occurred only in the high-grade lesions and was therefore related to lesion grade. Loss of cytokeratin 14 expression was also significantly more frequent in high-grade than in low-grade lesions (19 of 33 v 12 of 51; P < .01). In addition, cytokeratin 14 expression was significantly less frequent in the intermediate and superficial layers of low-grade SILs infected with high-risk HPVs than in those infected with low-risk HPVs (3 of 27 v 14 of 24; P < .001). These findings are consistent with in vitro data and suggest that abnormalities of both cell cycle control and squamous differentiation are important in HPV-associated neoplastic transformation. Topics: DNA, Viral; Female; Humans; Immunoenzyme Techniques; In Situ Hybridization; Keratin-14; Keratins; Papillomaviridae; Papillomavirus Infections; Polymerase Chain Reaction; Protein Precursors; Transcription Factor AP-1; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 2001 |
Four-color multiparameter DNA flow cytometric method to study phenotypic intratumor heterogeneity in cervical cancer.
Multiparameter DNA flow cytometry using a one-laser bench-top flow cytometer has been restricted to three different colors. The two laser FACSCalibur has recently been introduced, allowing four-color analysis. Therefore, we optimized and extended our three-color method (Corver et al., 1994, Corver et al. 1996) to a four-color analysis of phenotypic intra-tumor heterogeneity using a bench-top flow cytometer.. First, the effect of a range of different propidium iodide (PI) and TO-PRO-3 iodide (TP3) concentrations on the coefficient of variation (CV) of the DNA histograms was measured using paraformaldehyde-fixed lysolecithin-permeabilized peripheral blood lymphocytes (PBLs) and SiHa and HeLa cervical cancer cells. Second, labeling freshly isolated cervical cancers from solid tumors was optimized with a mixture of anti-keratin antibodies. Third, the FACSCalibur hardware was modified, thereby allowing the simultaneous measurement of allophycocyanin (APC) fluorescence (FL4) in combination with FL3 pulse processing (FL3-W vs. FL3-A). The optimized procedure was then applied to cell suspensions from four different human cervical cancers to study phenotypic intratumor heterogeneity. Cell suspensions were simultaneously stained for DNA (PI, fluorescence) and three cellular antigens: (a) the epithelial cell-adhesion molecule (Ep-CAM; APC fluorescence), (b) keratin (R-phycoerythrin [RPE] fluorescence) to identify the epithelial fraction, and (c) vimentin (fluorescein-isothiocyanate [FITC] fluorescence) to label stromal cells.. Overall, PI produced better CVs than did TP3. The optimal concentration of PI was 50-100 microM for all cells tested. Average CVs were 1.76% (PBL), 3.16% (HeLa), and 2.50% (SiHa). Optimal TP3 concentrations were 0.25-2.0 microM. Average CVs were 2. 58% (PBL), 5.16% (HeLa), and 3.96% (SiHa). Inter- or intra-DNA stem line heterogeneity of Ep-CAM expression was observed in the keratin-positive fractions. Vimentin-positive, keratin-negative cells were restricted to the DNA diploid fraction.. PI is a superior DNA stain to TP3 when using intact normal PBL and human cancer cells. Four-color high-resolution multiparameter DNA flow cytometry allows the identification of intratumor subpopulations using PI as DNA stain and FITC, RPE, and APC as reporter molecules. The FACSCalibur bench-top flow cytometer can be used for this purpose, allowing the application of this technique in clinical laboratories. Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Carbocyanines; Cell Adhesion Molecules; DNA; Epithelial Cell Adhesion Molecule; Female; Flow Cytometry; Fluorescent Antibody Technique; Fluorescent Dyes; Humans; Keratins; Lymphocytes; Phenotype; Phycocyanin; Propidium; Tumor Cells, Cultured; Uterine Cervical Neoplasms | 2000 |
Can initial serum cyfra 21-1, SCC antigen, and TPA levels in squamous cell cervical cancer predict lymph node metastases or prognosis?
The aim of this study was to determine whether lymph node metastases or prognosis can be predicted by initial serum Cyfra 21-1, tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) levels in squamous cell cervical cancer.. Pretreatment serum levels of 92 patients were correlated with clinicopathologic parameters and prognostic data. The clinical performance of the tests was evaluated by their receiver operating characteristic curves. The prognostic power of the variables was assessed using Cox regression analysis.. Serum levels of each marker were significantly related to tumor stage, size, and depth of infiltration. The clinical performance of each marker in predicting lymph node metastases or parametrial involvement was poor. In the stepwise Cox regression analysis, regarding patients with early stage cervical cancer (stage Ib/IIa, n = 63), tumor size (P = 0.0005) was the only independent prognostic factor for disease-free interval. Lymph node status (P = 0.0014), tumor size (P = 0.004), and parametrial involvement (P = 0.025) were independent risk factors for survival. Considering all patients with stages Ia through IVb disease, tumor size (P = 0.0001) and TPA level (P = 0. 026) were independent risk factors for disease-free interval, whereas tumor size (P = 0.0001) and parametrial involvement (P = 0. 0002) were risk factors for survival.. Pretreatment Cyfra 21-1, TPA, and SCC-Ag levels were strongly related to tumor burden, but insufficiently reliable for identifying patients at risk of the presence of lymph node metastases or parametrial involvement. Serum levels of each marker showed no independent prognostic value in early stage cervical cancer. Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Serpins; Tissue Polypeptide Antigen; Uterine Cervical Neoplasms | 2000 |
Ectopic production and localization of beta-human chorionic gonadotropin in lymphoepithelioma-like carcinoma of the cervix: a case report.
A 32-year-old woman underwent a suction curettage for missed abortion. The initial serum human chorionic gonadotropin (beta-hCG) level was 40 IU/ml. The histologic examination of the uterine curettage specimen showed scant strips of a poorly differentiated malignant neoplasm and no chorionic villi. The tumor showed strong immunoreactivity for cytokeratin (AE1/AE3) and beta-hCG but no reactivity for human placental lactogen. The combination of histologic appearance, beta-hCG immunoreactivity, and elevation of serum beta-hCG raised a strong suspicion for epithelioid trophoblastic tumor (ETT). Postcurettage serial serum beta-hCG levels remained in the range of 20 to 45 micrograms/ml. Computerized tomographic scan showed a 1.0-cm circumscribed mass in the upper endocervix. A radical hysterectomy and pelvic lymphadenectomy were performed. Gross examination of the hysterectomy specimen likewise showed a well-circumscribed mass in the upper endocervix. Histologic examination revealed an undifferentiated carcinoma accompanied by intense lymphoplasmacytic infiltrate. A final diagnosis of lymphoepithelioma-like carcinoma (LELC) was rendered. LELC with elevated serum beta-hCG level and immunoreactivity to beta-hCG should be distinguished from ETT in a small endocervical curettage sample. Topics: Abortion, Missed; Adult; Carcinoma, Squamous Cell; Chorionic Gonadotropin, beta Subunit, Human; Diagnosis, Differential; Female; Humans; Hysterectomy; Keratins; Lymphocytes; Necrosis; Placental Lactogen; Plasma Cells; Pregnancy; Trophoblastic Neoplasms; Uterine Cervical Neoplasms | 2000 |
Serum CYFRA 21-1 in cervical cancer patients treated with radiation therapy.
A fragment of cytokeratin 19, referred to as CYFRA 21-1, is abundant in the serum of many patients with malignant tumors and is recognized as one of the established tumor markers, especially for non-small-cell lung cancer. In this study, the clinical usefulness of CYFRA 21-1 was investigated in cervical cancer patients treated with radiation therapy with reference to squamous-cell-carcinoma-related antigen (SCC-Ag), a common tumor marker of cervical squamous cell carcinoma.. The serum levels of CYFRA 21-1 and SCC-Ag of 50 patients with squamous cell carcinoma of the uterine cervix were measured before and after radiation therapy.. CYFRA 21-1 was positive in 52% of the patients. The incidence increased with the stage of the cancer, and post-treatment increases were a sign of disease progression. During radiation, serum levels of CYFRA 21-1 decreased significantly and reflected the radiation effect well. In addition, CYFRA 21-1 was negative in all patients without distant metastasis at the end of radiation therapy. Compared with SCC-Ag, patients were less often positive for CYFRA 21-1, but there was a statistically positive correlation between the two markers (correlation matrix=0.69).. CYFRA 21-1 can be used in monitoring the outcome of patients with squamous cell carcinoma of the uterine cervix. It may be particularly useful for patients without SCC-Ag. Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Radiotherapy Dosage; Uterine Cervical Neoplasms | 2000 |
Distinction between HLA class I-positive and -negative cervical tumor subpopulations by multiparameter DNA flow cytometry.
The study of the molecular-genetic basis of heterogeneity of HLA class I expression in solid tumors is hampered by the lack of reliable rapid cell-by-cell isolation techniques. Hence, we studied the applicability of a flow cytometric approach (Corver et al.: Cytometry 2000;39;96-107).. Cells were isolated from five fresh cervical tumors and simultaneously stained for CD45 or vimentin (fluorescein isothiocyanate fluorescence), Keratin (R-phycoerythrin fluorescence), HLA class I (APC fluorescence), and DNA (propidium iodide fluorescence). A dual-laser flow cytometer was used for fluorescence analysis. Tissue sections from the corresponding tumors were stained for HLA class I antigens, keratin, vimentin, or CD45.. Flow cytometry enabled the simultaneous measurement of normal stromal cells (vimentin positive), inflammatory cells (CD45 positive), epithelial cells (keratin positive), and DNA content readily. Normal stromal/inflammatory cells served as intrinsic HLA class I-positive as well as DNA-diploid references. Good DNA histogram quality was obtained (average coefficient of variation < 4%). Intratumor keratin positive subpopulations differing in HLA class I expression as well as DNA content could be clearly identified. Losses of allele-specific HLA class I expression found by immunohistochemistry were also detected by flow cytometry.. We conclude that multiparameter DNA flow cytometry is a powerful tool to study loss of HLA class I expression in human cervical tumors. The method enables flow-sorting of discrete tumor and normal cell subpopulations for further molecular genetic analysis. Topics: Antibodies, Monoclonal; DNA, Neoplasm; Down-Regulation; Female; Flow Cytometry; Genetic Heterogeneity; Histocompatibility Antigens Class I; HLA-A Antigens; HLA-A11 Antigen; HLA-A24 Antigen; HLA-B Antigens; Humans; Keratins; Leukocyte Common Antigens; Ploidies; Uterine Cervical Neoplasms | 2000 |
Growth inhibitory effects and radiosensitization induced by fatty aromatic acids on human cervical cancer cells.
Evidences have been reported that phenylacetic (PA) and phenylbutyric (PB) fatty aromatic acids can exert tumor growth inhibition in vitro and in vivo. Moreover, clinical trials also showed some activity for these drugs to modulate the expression of genes implicated in tumor growth, metastasis, immunogenicity, and to potentiate the efficacy of cytotoxic agents. The aim of the study was to examine the effects of PA and PB on the growth as well as sensitization to cisplatin and radiation in human cervical cancer cells. The effects of PA and PB on the proliferative activity and apoptosis induction in cervical tumor tissue was investigated. Both PA and PB exhibited a time- and dose-dependent antiproliferative activity in SW756 and ME180 cell lines: after 72-h treatment, the IC50 (concentration able to inhibit 50% of cell growth) of PB was 1.9 +/- 0.2 mM and 1.5 +/- 0.2 mM in SW756 and ME180 cells, respectively, while the IC50 of PA was 13.0 +/- 1.7 mM and 10.0 +/- 1.2 mM in SW756 and ME180 cells, respectively. In tumor tissue biopsies obtained from patients affected by squamous cervical cancer, both drugs resulted in a marked reduction of the percentage of bromodeoxyuridine-labeled cells compared with untreated samples [19.0 +/- 1.63% in untreated tissues with respect to 1.30 +/- 0.54% and 4.20 +/- 2.50% of stained cells after treatment with PA (30 mM) (P < 0.0001) and PB (5 mM) (P < 0.0001), respectively]. Moreover, analysis of the staining with M30 monoclonal antibody revealed that PA (30 mM) and PB (5 mM) were able to produce a marked increase in the number of stained apoptotic nuclei with respect to untreated samples. Finally, PB and PA were shown to enhance the sensitivity of SW756 to radiation and to exert an additive effect when combined with cisplatin. A significant reduction of the processed form of p21ras and rhoB proteins in the membrane fraction of cells exposed to PA and PB was observed. When farnesol, which is able to circumvent the enzymatic step inhibited by PA and PB, was added to the medium only a partial reversal of the growth inhibition and potentiation of sensitivity to radiation induced by PA and PB were found. In conclusion, the growth inhibitory properties of fatty aromatic acids suggest that these molecules could represent the prototype of a new class of compounds with some therapeutic potential in cervical cancer. Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Apoptosis; Bromodeoxyuridine; Cell Cycle; Cell Division; Cisplatin; Combined Modality Therapy; DNA Fragmentation; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Fatty Acids; Female; Humans; Inhibitory Concentration 50; Keratins; Phenylacetates; Phenylbutyrates; Proto-Oncogene Proteins p21(ras); Radiation-Sensitizing Agents; rhoB GTP-Binding Protein; Time Factors; Tumor Cells, Cultured; Uterine Cervical Neoplasms | 2000 |
Can keratin 8 and 17 immunohistochemistry be of diagnostic value in cervical cytology? A feasibility study.
Based on results from evaluation of tissue sections from premalignant lesions of the uterine cervix, the authors examined the hypothesis that immunostaining of Papanicolaou-stained cytologic smears with monoclonal antibodies to keratins 8 and 17 allows detection of cervical intraepithelial neoplasia (CIN) with progressive potential. They also investigated whether detection of these two keratin subtypes could be of help in the analysis of normal and/or poor quality cytology smears.. Sixty-one Papanicolaou-stained smears, representing 25 normal smears, 8 CIN 1, 7 CIN 2, 18 CIN 3, and 3 cervical carcinomas, were stained with CAM 5.2 and E3, which are capable of detecting keratin 8 and 17, respectively. The percentages of immunoreactive normal, metaplastic, dysplastic, and malignant epithelial cells were determined.. In normal cervical smears, keratin 8 was detected in endocervical columnar cells and sporadically in immature squamous metaplastic cells. Keratin 17 was identified in reserve cells and frequently in immature squamous metaplasic cells. In CIN, the number of cases in which keratin 8 was present increased with the severity of the lesion. Keratin 17 was found in the majority of CIN lesions, irrespective of grade. Intensity of immunostaining and number of cells stained per lesion varied and were also not related to the severity of CIN.. The use of the keratin 8 antibody in normal cervical smears enabled the detection of endocervical cells in cases where they were thought to be absent, particularly in cases with severe inflammation. Staining with keratin 17 enabled the identification of reserve cells or immature metaplastic cells, which were often misinterpreted as parabasal cells. The application of antibodies to these subtypes of keratins in cervical cytology can to a certain extent help in the identification of CIN and may in future be tested in automated screening. Topics: Carcinoma, Squamous Cell; Cervix Uteri; Cytodiagnosis; Diagnosis, Differential; Epithelial Cells; Feasibility Studies; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Papanicolaou Test; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears | 1999 |
Differential expression of keratins 10, 17, and 19 in normal cervical epithelium, cervical intraepithelial neoplasia, and cervical carcinoma.
To examine the value of immunohistochemistry in defining a keratin profile to aid cervical histopathological diagnosis.. Immunohistochemical localisation of keratins 17, 10, and 19 was studied in 268 cervical biopsies from 216 women including normal epithelia (with and without human papilloma virus), low and high grade cervical intraepithelial neoplasia, and invasive carcinoma. The percentage of positive immunostaining was scored using a Kontron MOP videoplan image analyser.. All major categories of cervical epithelia expressed these keratins to varying degrees. The median percentage of immunostaining for keratin 10 was 40% in normal tissue compared with just 1% in invasive carcinoma (p < 0.0001). The medians for keratin 17 were 0% in the normal group and 80% in carcinomas (p < 0.0001). By contrast, there was no significant difference in staining for keratin 19. Using a combination of the keratin 10 and 17 percentages, it was possible to separate the carcinomas from the benign conditions with a sensitivity of 100% and a specificity of 93%. Further analyses within the groups revealed more extensive staining for keratins 10 and 19 in reserve cell hyperplasia, immature squamous metaplasia, and congenital transformation zone.. The morphological variety within the cervix is reflected, in part, by distinct keratin patterns. There are striking differences in the patterns of keratins 10 and 17 between infiltrating squamous carcinoma and normal cervical epithelia. Topics: Biomarkers, Tumor; Cervix Uteri; Diagnosis, Differential; Epithelium; Female; Humans; Keratins; Neoplasm Invasiveness; Neoplasm Proteins; Precancerous Conditions; Retrospective Studies; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1999 |
The evaluation of cytokeratin 18 expression in cervical squamous cell carcinoma.
Topics: Carcinoma, Squamous Cell; Evaluation Studies as Topic; Female; Humans; Immunoenzyme Techniques; Keratins; Uterine Cervical Neoplasms | 1999 |
Expression of transglutaminase K in normal cervix tissue and cervix carcinomas.
The localization and expression of transglutaminase K has been investigated immunohistochemically in normal cervix tissue (n = 15) and in cervix carcinomas (n = 23). The distribution of the transglutaminase K was compared with the staining patterns of cytokeratin 10, Ki-67, p53, and oestrogen and progesterone receptors in these tumours. Weak to strong membrane-bound immunoreactivity for transglutaminase K was detected in almost all cervix carcinomas analyzed. The immunostaining was heterogeneous, with visual differences between individual tumour cells. 66.7% of normal cervix tissues revealed no immunoreactivity for the transglutaminase K. In normal cervix tissue, the immunoreactivity was confined to upper cervix layers, predominantly to the superficial and intermediate cell layers. The intensity of both the immunostaining and the number of transglutaminase K-positive cells were upregulated in cervix carcinomas as compared to normal cervix tissue. When the coexpressions of transglutaminase K with markers of proliferation and differentiation were analyzed, no statistically significant correlation was found. Our findings indicate that (1) transglutaminase K is upregulated at the protein level in cervix carcinomas as compared to normal cervix tissue; (2) upregulation of the transglutaminase K in cervix carcinoma is not exclusively induced by alterations of epithelial differentiation or proliferation, but by different, unknown mechanisms; and (3) upregulation of transglutaminase K in cervix carcinomas may play an important role for the regulation of tumour invasive properties by modulating cell-cell interactions. Topics: Biomarkers; Cell Differentiation; Cell Division; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Receptors, Estrogen; Receptors, Progesterone; Transglutaminases; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms | 1999 |
Frequent expression of beta-human chorionic gonadotropin (beta-hCG) in squamous cell carcinoma of the cervix.
Human chorionic gonadotropin (beta-hCG) has been detected within tissue homogenates, culture fluid, and sera of patients with squamous cell carcinoma of the cervix. Studies regarding in vivo localization of beta-hCG in squamous cell carcinoma of the cervix are scant and conflicting. Cervical samplings (biopsy and/or curettage specimens) of 63 cases of poorly differentiated invasive squamous cell carcinoma of the cervix were initially stained by the immunoperoxidase technique for the presence of beta-hCG and human placental lactogen (hPL). Based on beta-hCG reactivity, patients were divided into beta-hCG-positive and beta-hCG-negative groups. Thirty-three of the 63 (52%) cases showed localization of beta-hCG in tumor cells. Subsequent specimens of patients, who underwent surgical treatment, were likewise examined for beta-hCG reactivity. These surgical specimens showed focal beta-hCG reactivity in the beta-hCG-positive group only. The beta-hCG reactivity was seen in both high-grade SIL (CIN III), invasive squamous cell carcinoma, and its metastases. The focal beta-hCG reactivity was predominantly confined to the peripheral tumor cells at the stromal-epithelial interface in noninvasive and invasive lesions. Intensity of immunostaining was moderate to strong. The beta-hCG staining was observed in different cancer stages and in various age groups. No hPL reactivity was seen in any cases. Poorly differentiated squamous cell carcinoma of uterine cervix showing immunoreactivity for beta-hCG should be distinguished from choriocarcinoma and other trophoblastic tumors. Topics: Adult; Aged; Carcinoma, Squamous Cell; Chorionic Gonadotropin, beta Subunit, Human; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Retrospective Studies; Uterine Cervical Neoplasms | 1999 |
Cytokeratin 10/13, 14, 7, 8, and 18 in invasive squamous cell carcinoma and adenocarcinoma of the uterine cervix.
Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Female; Humans; Keratins; Uterine Cervical Neoplasms | 1999 |
Cancer of the uterine cervix: sensitivity and specificity of serum Cyfra 21.1 determinations.
The purpose was to evaluate the usefulness of serum Cyfra 21.1 assay for the monitoring of patients with uterine cervix cancer.. Pre-treatment sera and complete follow-up of the patients were available for SCC and Cyfra 21.1 for 79 patients Another group of 50 patients was studied to evaluate the specificity, sensitivity, negative or positive predictive values of the markers. The cut-off value for Cyfra 21.1 (1.1 ng/ml) was established by ROC curve analysis.. A positive or negative concordance between SCC and Cyfra 21.1 was observed in 65.8% of the cases. Positive SCC and negative Cyfra 21.1 were found in 22.8% of the sera, while the inverse was observed in 11.4% of the cases. The mean concentrations of SCC and Cyfra 21.1 were correlated to FIGO stages, with Cyfra 21.1 being elevated in 100% of stages III and IV. Cyfra 21.1 was also correlated with the extension of the cancer, and to the presence of metastases. The mean concentrations of both markers were significantly higher in the sera of patients with constant progression (P < or = 0.0019). Analysis of 186 results from 91 patients followed-up with a median of 3.29 years showed a sensitivity of 89.5% for Cyfra 21.1, 75.0% for SCC, and a specificity of 86.4% and 99.1%, respectively. The positive predictive values were 91.9% for Cyfra 21.1 and 98.3% for SCC, and the negative predictive values 92.7% and 85.2%, respectively. Median lead times, calculated from the records of 18 selected patients with complete resection of the tumour, were found to be 60 days for Cyfra 21.1 and 50 days for SCC (P > 0.05).. In cervical cancer Cyfra 21.1 is very well-correlated to the tumour burden and the extent of the disease. In the case of recurrence, this marker rises more often than SCC. We therefore propose the use of Cyfra 21.1 for the monitoring of cervical cancer. Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Middle Aged; Prospective Studies; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Uterine Cervical Neoplasms | 1998 |
[The change of localization on cytokeratin of uterine cervix and the relationship to the pattern of invasion in cervical cancer].
An immunohistochemical study of 63 cases of uterine cervical cancer was undertaken. It was confirmed that the biological character of the cancer cells derived from the reserve cells changed over the course of invasion. Squamous cell carcinoma had positive keratin antibodies such as CK 10/13 (DE-K 13), CK 14 (NCL-LL 002) and CK 7 (OV-TL 12/30). In invasive squamous cell carcinoma, CK 14 positive cells were piled up and tended to be stained positive by PCNA and laminin. There were two types of staining, one of which revealed CK 14 strongly positive, and the other weakly positive. The first type differed from the second in depth and localization. The cells on the margin of a cluster of cancer cells were stained positive with CK 14 as in normal basal cells. The results obtained suggested: 1) squamous cell carcinoma has not only the character of normal squamous cells, but also that of the cells derived from the cervical glands. 2) cancer cells may develop in accordance with the character of basal cells, and the patterns of invasion change according to the character of basal cells in cancer tissue. Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness; Proliferating Cell Nuclear Antigen; Uterine Cervical Neoplasms | 1998 |
Value of a panel of antibodies to identify the primary origin of adenocarcinomas presenting as bladder carcinoma.
Adenocarcinomas may arise primarily from the urinary bladder, but secondary involvement from adenocarcinomas arising in adjacent organs is more common. In the present study we tried to differentiate primary urinary bladder adenocarcinomas from adenocarcinomas arising from the surrounding organs, based on their antigen profiles in routinely processed, paraffin-embedded tissue specimens. We analysed the staining results using stepwise linear discriminant analysis.. We investigated the usefulness of a panel of antibodies against cytokeratin 7, E48, cytokeratin 20, PSA, PSAP, CEA, vimentin, OC125 and HER-2/neu, to discriminate primary bladder adenocarcinoma from adenocarcinomas arising from the prostate, urachus, colon, cervix, ovary and endometrium. In the differential diagnosis with urinary bladder adenocarcinoma, an overall correct classification was reached for 77% and 81% of urachal and colonic carcinomas, respectively, using CEA, for 93% of prostatic adenocarcinomas using PSA, for 82% and 70% of cervical and ovarian adenocarcinomas, respectively, using OC125, and for 91% of endometrial adenocarcinomas using vimentin. Adding other antibodies did not improve the classification results for any of these differential diagnoses.. For the surgical pathologist, a panel of antibodies consisting of CEA, PSA, OC125 and vimentin is helpful to differentiate primary urinary bladder adenocarcinomas from adenocarcinomas originating from prostate and endometrium, less helpful in differentiation with urachal carcinoma, and not helpful in differentiation with colonic, cervical and ovarian carcinoma. Topics: Abdominal Neoplasms; Acid Phosphatase; Adenocarcinoma; Antibodies, Monoclonal; Antibody Specificity; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Papillary; Cell Adhesion Molecules; Diagnosis, Differential; Endometrial Neoplasms; Female; Glycoproteins; GPI-Linked Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Neoplasms, Unknown Primary; Ovarian Neoplasms; Prostate; Prostate-Specific Antigen; Receptor, ErbB-2; Urachus; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms; Vimentin | 1998 |
Goblet-cell mucinous epithelium lining the endometrium and endocervix: evidence of metastasis from an appendiceal primary tumor through the use of cytokeratin-7 and -20 immunostains.
Differential staining with cytokeratin (CK)-7 and CK-20, two members of a complex family of proteins in human epithelial cells, proved critical in showing that the extremely well-differentiated goblet-cell (intestinal) mucinous epithelium lining the surface of the endometrium and endocervix in two patients and the fallopian tube in one was identical to that of the coincident appendiceal neoplasms. One of these patients also had a large ovarian tumor that grossly and microscopically resembled a mucinous cystadenoma of borderline malignancy and would have been considered primary except for the CK stains (CK-20 positive and CK-7 negative), which suggested metastasis from the appendix, presumably by a transtubal route. Topics: Appendiceal Neoplasms; Biopsy; Endometrial Neoplasms; Epithelium; Fallopian Tubes; Female; Goblet Cells; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; Mucins; Ovarian Neoplasms; Uterine Cervical Neoplasms | 1998 |
Immunohistochemical analysis of 1,25-dihydroxyvitamin D3 receptor in cervical carcinoma.
The immunohistochemical localization and expression of 1,25-dihydroxyvitamin D3 receptors (VDR) has been investigated in normal human cervical tissue (n = 15) and in cervical carcinomas (n = 23). VDR immunoreactivity (monoclonal antibody 9A7gamma) was compared with the staining patterns of transglutaminase K, cytokeratin 10 and Ki-67 in these tumours. Moderate to strong nuclear immunoreactivity for VDR was detected in almost all cervical carcinomas analysed. VDR staining was homogeneous, with no visual differences between individual tumour cells. Some 60% of normal cervical tissues revealed weak immunoreactivity for VDR. In normal cervical tissue, nuclear VDR staining was confined to the lower cervical layers, predominantly to the basal cell layer. Both the intensity of VDR immunostaining and the number of VDR-positive cells were up-regulated in cervical carcinomas compared with normal cervical tissue. No visual correlation was found for the coexpression of VDR with markers of proliferation and differentiation. Our findings indicate that: (1) cervical tissue may be a new target organ for therapeutically applied vitamin D analogues; (2) VDR is up-regulated at the protein level in cervical carcinomas compared with normal cervical tissue; (3) up-regulation of VDR in cervical carcinoma is induced not exclusively by alterations in epithelial differentiation or proliferation, but by different, unknown mechanisms; and (4) calcitriol and new vitamin D analogues exerting fewer calcaemic side-effects may be promising new drugs for the treatment or chemoprevention of metastasizing cervical carcinomas as well as of cervical precancerous lesions. Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Cell Nucleus; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Receptors, Calcitriol; Transglutaminases; Uterine Cervical Neoplasms | 1998 |
Coexpression of cholesterol sulfate and cytokeratin as tumor markers in well-differentiated squamous cell carcinoma of the human uterine cervix.
The expression of cholesterol sulfate (CS) is known to increase during squamous differentiation of keratinocytes and to activate the epsilon, eta, and zeta forms of protein kinase C as a signal transduction molecule for the subsequent expression of transglutaminase-1 (TG-1) and cytokeratins. To gain further insight into the regulation of cellular differentiation and tumorigenesis by CS, we examined the concentration and the potential for synthesis of CS in seven and four surgical specimens from human ovarian and uterine cervical cancer patients, respectively, and eight cell lines established from human uterine cervical cancer patients and compared them for the rate of expression of cytokeratin. CS was present in all of the uterine cervical cancer tissue specimens but only in the mucinous type of cystadenocarcinoma among ovarian cancer tissue specimens, and cytokeratin was highly expressed in the tissues with a high concentration of CS, which were classified as well-differentiated on the basis of morphological examination. Similarly, cells derived from a keratinizing type of well-differentiated cervical carcinoma demonstrated strong potential for synthesis of CS, stained positive with anti-cytokeratin antibody, and exhibited a higher specific activity of TG-1, whereas the cells without CS did not stain positive with anti-cytokeratin antibody and exhibited a lower specific activity of TG-1. These findings indicate that CS is coexpressed with TG-1 and cytokeratin in the well-differentiated types of squamous cell cancers as a tumor marker. Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cholesterol Esters; Female; Humans; Immunohistochemistry; Keratins; Lipid Metabolism; Lipids; Ovarian Neoplasms; Tumor Cells, Cultured; Uterine Cervical Neoplasms; Uterine Neoplasms | 1998 |
Increased expression of cytokeratins 14, 18 and 19 correlates with tumor progression in the uterine cervix.
The expression of cytokeratins (CKs) in normal cervical epithelium, low grade squamous intraepithelial lesions (SIL), high grade SILs and squamous cell carcinoma (SCC) were analyzed using four different monoclonal antikeratin antibodies. In normal cervical epithelium, CK 18 showed strong immunoreactivity in basal and parabasal layers. CK 19 and 14 were expressed only in the basal layer while CK 13 was found selectively n the spinal cells. As the lesions progressed from low grade SIL to high grade SIL, immunoreactivity of CK 18, 19 and 14 in the basal cell compartment increased while the expression of CK 13 decreased. In SCC, as well-differentiated tumors showed decreased immunoreactivity for CK 18, 19 and 14 with CK 13 showing a strong and focal (localized) immunoreactivity. Undifferentiated carcinomas totally lacked CK 13 reactivity. Our findings therefore suggest that expression of CK 18, 19 and 14 may be directly related to tumor grade and CK 13 may be a marker of differentiation in cervical lesions. Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1997 |
Cytokeratins and the evaluation of tumor differentiation in squamous lesions of the uterine cervix.
The differential expression of cytokeratins in epithelial or squamous cells has been demonstrated to be altered during the process of carcinogenesis. This altered expression of cytokeratins (CKs) may be closely related with epithelial differentiation and may remain stable in malignant tumors. In the present study an analysis using two monoclonal antibodies, CK 8.12 antibody specific for CK type 13 and 16 and CK 8.60 antibody specific for CK type 1, 10 and 11 was done in different grades of lesions in the uterine cervix. Changes from the normal expression pattern were seen in high grade Squamous intraepithelial lesions (SIL) (CIN-2/3) and invasive squamous cell carcinoma (SCC). No conspicuous difference in the staining expression between normal/benign cervical tissue and low grade SIL (CIN-I) was evident. Statistical analysis also revealed a significant correlation between the expression of these CK types to the differentiation status of the cervical lesions analyzed. Alterations in the expression of these CKs can be correlated to the differentiation pathway which may be deregulated during cervical carcinogenesis. The findings of the present study suggest that the expression of CK types 13 and 16 and 1, 10 and 11 using CK 8.12 and CK 8.60 antibodies respectively may serve as markers of differentiation in cervical squamous neoplasms. Topics: Adult; Analysis of Variance; Carcinoma, Squamous Cell; Cell Differentiation; Cell Transformation, Neoplastic; Cervix Uteri; Female; Humans; Immunochemistry; Keratins; Middle Aged; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1997 |
Quantitative determination of the epidermal growth factor receptor in cervical cancer and normal cervical epithelium by 2-color flow cytometry: evidence for down-regulation in cervical cancer.
Expression of epidermal growth factor receptor (EGFR) was quantified by 2-color flow cytometry in cervical cancer (n = 73) and normal cervical epithelium (n = 11). EGFR was determined using a murine monoclonal EGFR antibody, and number of bound antibodies was quantified adding calibration beads with defined antigenic binding sites. Tumor cells were identified by simultaneous DNA staining. Epithelium of normal cervical tissue was detected by labeling for cytokeratin. Results were compared with EGFR quantification by autoradiography on cryostat sections using a radioligand binding assay. A high degree of correlation was found between the 2 methods. In cervical carcinomas 14,600 binding sites/cell (median; range, 160-283,000 binding sites/cell) were detected, considerably less compared with normal cervical squamous epithelium, which was 30,700 binding sites/cell (median; range, 19,900-44,000 binding sites/cell). This finding clearly contrasts with other reports of enhanced EGFR expression in cervical cancer. The discrepancy may be explained by contamination of tissue homogenates used for radioligand or enzyme immunosorbent assays by non-epithelial tissue elements with low or absent EGFR expression. Interference with quantitative EGFR determination in epithelial cells may result in false low estimates of EGFR expression predominantly in normal cervical tissue. This should be avoided by identifying tumor and normal epithelial cells prior to analysis. In our study, 63% of cervical cancers expressed low levels of EGFR compared with normal cervical epithelium, and only 10% showed overexpression. There is evidence that cervical carcinomas overexpressing EGFR represent a small, but biologically distinct group of cervical cancers exhibiting enhanced aggressiveness associated with poor survival of the patients. Topics: Antibodies, Monoclonal; Autoradiography; Binding Sites, Antibody; Biomarkers; Cervix Uteri; Down-Regulation; Epidermal Growth Factor; Epithelial Cells; Epithelium; ErbB Receptors; Female; Flow Cytometry; Humans; Iodine Radioisotopes; Keratins; Prospective Studies; Regression Analysis; Uterine Cervical Neoplasms | 1997 |
Serum M3/M21 in cervical cancer patients.
Cytokeratins are polypeptides which constitute a subclass of intermediate filaments in epithelial cells. The serum tumour marker M3/M21 is based on monoclonal antibodies against the epitopes M3 and M21 of cytokeratin 18. In the present study, we measured M3/M21 serum levels in 50 patients with FIGO stage IB-IIB cervical cancer and in 50 control subjects using a two-site radiometric immunoassay directed against soluble fragments of cytokeratin 18. Median serum levels of M3/M21 in patients with cervical cancer and in normal controls were 70.6 U/ml (range 0-397.7) and 6.5 U/ml (range 0-205.2), respectively (Mann-Whitney U-test, P = 0.0001). Median serum levels of M3/M21 prior to therapy and 4 weeks after therapy were 104.2 U/ml (range 24.6-397.7) and 39.3 U/ml (range 0-234.7), respectively (Mann-Whitney U-test, P = 0.004). We found a significant correlation between elevated M3/M21 serum levels and metastatic disease in pelvic lymph nodes (Mann-Whitney U-test, P = 0.002). 24 patients relapsed after complete remission. In these patients, elevated M3/M21 serum levels before the detection of relapse by computed tomography was observed in 13 cases. Considering these preliminary results, further studies with an increased number of patients are justified to clarify the prognostic value and the monitoring abilities of M3/M21 in cervical cancer patients. Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carrier Proteins; Epitopes; Female; Humans; Keratins; Predictive Value of Tests; Retrospective Studies; Uterine Cervical Neoplasms | 1997 |
The independence of intrinsic radiosensitivity as a prognostic factor for patient response to radiotherapy of carcinoma of the cervix.
A study was made of the prognostic value of pretreatment measurements of tumour radiosensitivity (surviving fraction at 2 Gy, SF2) in 128 patients with stage I-III carcinomas of the uterine cervix undergoing radiotherapy. The median follow-up time was 47 months. In a univariate analysis stratifying patients according to the median value, radiosensitivity was a significant prognostic factor for overall survival, local control and metastasis-free survival. The 5-year survival rate for tumours with SF2 values below the median was 81% and was significantly greater than the rate of 51% for those with SF2 values above the median. In bivariate analyses, SF2 was shown to be independent of disease stage, tumour grade, patient age, colony-forming efficiency and tumour diameter. In a multivariate analysis, radiosensitivity was the most important variable and, after allowing for this, only stage was a significant independent predictor of treatment outcome. These data indicate that, in carcinoma of the cervix treated with radiotherapy, pretreatment tumour intrinsic radiosensitivity is an important prognostic parameter and contributes to prognosis independently of other established and putative parameters. Topics: Adenocarcinoma; Adult; Age Factors; Aged; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Prognosis; Radiation Tolerance; Survival Rate; Time Factors; Treatment Outcome; Uterine Cervical Neoplasms | 1997 |
Cervical squamous cell carcinoma in situ with intraepithelial extension to the upper genital tract and invasion of tubes and ovaries: report of a case with human papilloma virus analysis.
A 55-year-old woman, who was found to have malignant squamous cells on a routine cervical smear, underwent a conization biopsy, followed by hysterectomy with bilateral salpingo-oophorectomy. No gross tumor was present in the uterus, but both ovaries, which were of normal size, contained multiple cysts filled with light brown, soft material. Microscopic examination showed squamous cell carcinoma in situ of the cervix with contiguous spread to the endometrium, fallopian tubes, and ovaries; squamous cell carcinoma extensively replaced the endometrial and tubal epithelium, focally invaded the wall of the fallopian tubes, and involved the parenchyma of both ovaries. Although an invasive cervical carcinoma occasionally spreads to the ovary, this case illustrates that exceptionally an in situ tumor spreads along the epithelium of the upper genital tract and the ovarian surface and invades the ovary and tubes. The detection of human papillomavirus DNA in the cervical, endometrial, tubal, and ovarian tumors by the polymerase chain reaction suggests a role for human papilloma virus infection in this case. Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Endometrial Neoplasms; Fallopian Tube Neoplasms; Female; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Middle Aged; Ovarian Neoplasms; Papillomaviridae; Uterine Cervical Neoplasms | 1997 |
Resistance to retinoic acid and altered cytokeratin expression of human papillomavirus type 16-immortalized endocervical cells after tumorigenesis.
Human papillomaviruses (HPVs) and cigarette smoking are epidemiologically associated with cervical cancer. We recently found that HEN-16 and HEN-16-2 HPV type 16-immortalized endocervical cells form tumors after treatment with cigarette smoke condensate and derived 2 tumor cell line cultures, HEN-16T and HEN-16-2T, respectively. Here, we examine the molecular pathologic effect of tumorigenesis. HEN-16T and HEN-16-2T exhibit unchanged status and expression of integrated HPV 16 DNA. However, the expression of the cytokeratin CK7 and CK13 endocervical cell markers is more homogeneous in monolayer and organotypic raft cultures after tumorigenesis. For the effect of retinoic acid on monolayers for growth inhibition, HEN-16T were significantly less sensitive than the normal and immortalized non-tumorigenic cells. HEN-16-2T were completely resistant. Moreover, the rafts from both tumorigenic cell line cultures were resistant to retinoic acid and continued to display thick rafts and homogeneous severe dysplasia/carcinoma in situ. In contrast, the non-malignant HEN-16 and HEN-16-2 rafts were thinner, and treatment with retinoic acid blocked the formation of severe dysplasia, reconstructing an epithelium resembling that of the normal endocervix. Our results support the significance of non-viral factors in the mechanism by which cigarette smoking induces tumorigenesis in the late stages of HPV-initiated progression to cervical cancer. Importantly, our data indicate that the sensitivity to retinoic acid of the HPV-containing endocervical cells is lost following tumorigenesis in vitro and possibly in women. Topics: Cell Division; Cell Line, Transformed; Cell Transformation, Neoplastic; Cell Transformation, Viral; DNA, Viral; Drug Resistance; Female; Humans; Keratins; Keratolytic Agents; Papillomaviridae; Tretinoin; Uterine Cervical Neoplasms | 1996 |
Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice.
High-risk human papillomaviruses (HPVs), including type 16, have been identified as factors in cervical carcinogenesis. However, the presence and expression of the virus per se appear to be insufficient for carcinogenesis. Rather, cofactors most likely are necessary in addition to viral gene expression to initiate neoplasia. One candidate cofactor is prolonged exposure to sex hormones. To examine the possible effects of estrogen on HPV-associated neoplasia, we treated transgenic mice expressing the oncogenes of HPV16 under control of the human keratin-14 promoter (K14-HPV16 transgenic mice) and nontransgenic control mice with slow release pellets of 17beta-estradiol. Squamous carcinomas developed in a multistage pathway exclusively in the vagina and cervix of K14-HPV16 transgenic mice. Estrogen-induced carcinogenesis was accompanied by an incremental increase in the incidence and distribution of proliferating cells solely within the cervical and vaginal squamous epithelium of K14-HPV16 mice. Expression of the HPV transgenes in untreated transgenic mice was detectable only during estrus; estrogen treatment resulted in transgene expression that was persistent but not further upregulated, remaining at low levels at all stages of carcinogenesis. The data demonstrate a novel mechanism of synergistic cooperation between chronic estrogen exposure and the oncogenes of HPV16 that coordinates squamous carcinogenesis in the female reproductive tract of K14-HPV16 transgenic mice. Topics: Animals; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Chloramphenicol O-Acetyltransferase; Delayed-Action Preparations; Estradiol; Female; Genes, Viral; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Mice; Mice, Transgenic; Oncogenes; Papillomaviridae; Proliferating Cell Nuclear Antigen; Promoter Regions, Genetic; RNA, Messenger; Uterine Cervical Neoplasms; Vaginal Neoplasms | 1996 |
Analysis of response to radiation therapy of patients with cervical adenocarcinoma compared with squamous cell carcinoma. MIB-1 and PC10 labeling indices.
The MIB-1 monoclonal antibody is a marker of cycling cells and the PC10 monoclonal antibody is a marker of proliferating cell nuclear antigen in paraffin sections. This study was conducted to elucidate the difference in response to radiotherapy (RT) between cervical adenocarcinomas and squamous cell carcinomas, focusing on cell proliferation.. A total of 196 biopsy specimens taken from the cervical carcinomas of 14 consecutive patients with adenocarcinoma and 62 patients with squamous cell carcinoma before and after RT at doses of 9 and 27 Grays (Gy) were investigated for MIB-1 and PC10 immunoreactivities.. In adenocarcinomas, the mean MIB-1 labeling indices before and after RT at 9 and 27 Gy were 28%, 21%, and 26%, respectively, whereas the mean PC10 labeling indices were 15%, 13%, and 14%, respectively. In squamous cell carcinomas, the mean MIB-1 labeling indices before and after RT at 9 and 27 Gy were 38%, 53%, and 26%, respectively, and the mean PC10 labeling indices were 23%, 23%, and 11%, respectively.. Cervical adenocarcinomas have a lower cycling cell population and their indices show no change during RT. Squamous cell carcinomas have a higher cycling cell population and show a transient increase of the MIB-1 cycling cell population at 9 Gy of RT. These findings suggest a difference in response to RT between adenocarcinomas and squamous cell carcinomas. Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Adenosquamous; Carcinoma, Endometrioid; Carcinoma, Squamous Cell; Cell Cycle; Cell Nucleus; Female; Humans; Keratins; Ki-67 Antigen; Neoplasm Proteins; Neoplasm Staging; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Treatment Outcome; Uterine Cervical Neoplasms | 1996 |
Expression of Ep-CAM in cervical squamous epithelia correlates with an increased proliferation and the disappearance of markers for terminal differentiation.
Ep-CAM, an epithelial adhesion molecule, is absent in normal squamous epithelia but can be detected in some squamous carcinomas. Using a panel of monoclonal antibodies to keratinocyte differentiation and proliferation markers, we investigated the association of EP-CAM expression with differentiation-related and/or neoplastic changes in cervical epithelium. Normal endocervical glandular epithelium (Both columnar and reserve cells) appeared strongly positive for EP-CAM, whereas ectocervical squamous epithelial cells did not express this molecule. Expression of Ep-CAM (in basal cells) was sometimes observed in morphologically normal ectocervical tissue but only in areas bordering cervical intraepithelial neoplasia (CIN) lesions. At the early stages of neoplasia the expression of Ep-CAM was regularly present in squamous epithelium, in general consistent with the areas of atypical, undifferentiated cells. Thus, in CIN grades I and II, the basal/suprabasal layers of the epithelia were positive, whereas in CIN grade III lesions, up to 100% of the cells over the whole thickness of the epithelium sometimes excluding the very upper layers, expressed Ep-CAM. A clear increase, not only in number of positive cells but also in levels of Ep-CAM expression (intensity) was observed during progression from CIN I to CIN III. Expression of Ep-CAM in ectocervical lesions did not coincide with a reappearance of the simple epithelium cytokeratins (CK8 and CK18). On the other hand, expression of Ep-CAM in atypical cells of CIN lesions correlated with the disappearance of CK13, which normally marks cells undergoing squamous differentiation. As was shown with Ki-67, a marker for proliferating cell populations, the areas of Ep-CAM expression were also the areas of enhanced proliferation. Cells expressing Ep-CAM did not express involucrin, a marker for cells committed to terminal differentiation. In the majority of both squamous and adenocarcinomas of the cervix a strong expression of Ep-CAM was observed, although some decrease in the expression (both the intensity and the number of positive cells), as compared with CIN III lesions, was observed in the areas of squamous differentiation. This study demonstrates that the expression of Ep-CAM in cervical squamous epithelium is associated with abnormal proliferation of cell populations that are not committed to terminal differentiation. Topics: Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Cell Adhesion Molecules; Cell Differentiation; Cell Division; Cervix Uteri; Epithelial Cell Adhesion Molecule; Epithelium; Female; Humans; Keratins; Metaplasia; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1996 |
Study of a new tumor marker, CYFRA 21-1, in squamous cell carcinoma of the cervix, and comparison with squamous cell carcinoma antigen.
The diagnostic value of a new tumor marker, CYFRA 21-1, was studied in the blood samples collected from 22 controls, and 87 pre-treatment patients with squamous cell carcinoma of the cervix. Sensitivity and specificity of CYFRA 21-1 was compared with those of squamous cell carcinoma antigen (SCC) measured in the sera of the same patients. Serum CYFRA 21-1 levels were higher in patients with squamous cell carcinoma than in controls (p < 0.05), and correlated with FIGO stage (Stage IIb-IV vs. Stage Ib-IIa, p = 0.0477). Using 2.5 ng/ml as cut-off value, elevated CYFRA 21-1 levels were found in 13.6% of controls, 34.8% of patients with Stage Ib-IIa squamous cell carcinoma of the cervix, and 63.5% of patients with Stage IIb-IV squamous cell carcinoma of the cervix. However, there was less sensitivity and specificity of CYFRA 21-1 than those of SCC in detecting squamous cell carcinoma of the cervix. CYFRA 21-1 may not be a better tumor marker than SCC for squamous cell carcinoma of the cervix. Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratins; Middle Aged; Peptide Fragments; Reference Values; Serpins; Uterine Cervical Neoplasms | 1996 |
[Immunohistochemical study of cytokeratin and vimentin expression in mixed type of adenocarcinoma and squamous cell carcinoma].
To clarify the pattern of cytokeratin and vimentin expression in mixed adenocarcinoma and squamous cell carcinoma of the uterine cervix, twenty-three cases of formalin-fixed paraffin-embedded specimen were examined immunohistochemically using a panel of four different monoclonal anti-cytokeratin antibodies and anti-vimentin antibody. Fifty-seven cases of benign or malignant tissue were selected for controls. The results were summarized as follows. 1) In four cases of co-existing adenocarcinoma and squamous cell carcinoma, their immunostaining patterns were compatible with original histological cell type. 2) In four cases of adenoacanthoma, high molecular weight-cytokeratin (HCK) was positive in each acanthomatous component and only a small part of one adenocarcinomatous component. 3) In twelve cases of cervical adenosquamous carcinoma, HCK were positive in four adenocarcinomatous components. Out of eight cases with non-stained adenocarcinomatous components, six cases showed negativity for HCK even in the squamous cell carcinomatous component. 4) Though vimentin was negative in all cases of mixed type of cervical carcinoma, some cases of mixed type endometrial carcinoma were stained positively for vimentin. It was indicated from our study that adenosquamous carcinoma of the cervix could originate either in reserve cells or columunar epithelium and that vimentin positive cases could originate in the endometorial gland. Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Paraffin Embedding; Uterine Cervical Neoplasms; Vimentin | 1996 |
Serum levels of cytokeratin 19 fragments in cervical cancer.
Serum levels of a cytokeratin 19 fragment, Cyfra 21-1, were measured using an immunoradiometric assay in 33 women before initial treatment and in 8 women with recurrent tumor. The serum level of Cyfra 21-1 was significantly increased in women with tumors of advanced stage (FIGO) and those with recurrence. The incidence of positivity for Cyfra 21-1 tended to increase with tumor spread. Compared with squamous cell carcinoma (SCC) antigen, the sensitivity of Cyfra 21-1 was comparable to that of SCC antigen. The serum level of Cyfra 21-1 and that of SCC antigen showed a positive correlation. While the use of the serum Cyfra 21-1 level may be limited in cervical cancer by its relatively low sensitivity, a combination assay of Cyfra 21-1 and SCC antigen may be useful in the diagnosis and follow-up of patients with cervical squamous cell carcinoma. Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma, Squamous Cell; Female; Humans; Immunoradiometric Assay; Keratins; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Peptide Fragments; Serpins; Uterine Cervical Neoplasms | 1996 |
Differential regulation of human ectocervical epithelial cell line proliferation and differentiation by retinoid X receptor- and retinoic acid receptor-specific retinoids.
Retinoids are important regulators of human papillomavirus (HPV)-immortalized cervical epithelial cell differentiation and have been successfully used in the treatment of HPV-involved cervical cancer. In the present study, we examine the effects of a series of natural and synthetic retinoids on differentiation and proliferation of HPV-16-positive lines, ECE16-1 and CaSki. Retinoic acid receptor alpha (RAR alpha), RAR gamma, and retinoid X receptor alpha (RXR alpha) are the major retinoid receptor subtypes expressed when ECE16-1 cells are grown in retinoid-free medium. Our results indicate that ligands that interact with RARs only or both RARs and RXRs, including all-trans-retinoic acid (all-trans-RA), 9-cis-retinoic acid (9-cis-RA), 13-cis-retinoic acid (13-cis-RA), and several synthetic retinoids, suppress ECE16-1 cell proliferation, regulate expression of the retinoid-responsive differentiation marker cytokeratin K5, and increase RAR beta mRNA levels. In contrast, ligands that specifically interact with RXRs do not suppress proliferation and are less efficient regulators of gene expression. CaSki cells express greatly reduced RAR and RXR levels compared to ECE16-1 cells. However, both RAR- and RXR-specific ligands increase CaSki number by > or = 20%. In addition, RXR-specific ligands suppress cytokeratin K5 mRNA levels slightly, compared to RAR-specific ligands that strongly suppress K5 mRNA levels. We also compare the effects of these agents on the proliferation of other cervical cell lines, including ECE16-D2, ME180, and SiHa cells. ECE16-D2 and ME180 cells are growth suppressed by RAR-specific, but not RXR-specific, retinoids. SiHa cells are not responsive to either class of retinoid. Our results indicate that: (a) the response of different human cervical cell lines varies following treatment with receptor type-specific retinoids; and (b) the relationship between retinoid regulation of proliferation and differentiation can be uncoupled. Topics: Cell Differentiation; Cell Division; Cell Transformation, Viral; Female; Humans; Keratins; Papillomaviridae; Receptors, Retinoic Acid; Retinoid X Receptors; Retinoids; RNA, Messenger; Transcription Factors; Tumor Cells, Cultured; Uterine Cervical Neoplasms | 1996 |
DNA cell-cycle analysis of cervical cancer by flow cytometry using simultaneous cytokeratin labelling for identification of tumour cells.
DNA ploidy and cell-cycle distribution were determined by flow cytometry in fresh tumour tissue of 53 cervical carcinomas. Epithelial cells were labelled by a fluorescein-isothiocyanate-conjugated cytokeratin antibody (CK6, CK18) to study the influence of contaminating stromal and inflammatory cells on results of cell-cycle analysis of tumour cells. Without identification of cytokeratin-positive cells 30/53 (57%) tumours were found to be DNA-aneuploid compared to 43/53 (81%) after gating for cytokeratin. Only 7 of 15 DNA-multiploid tumours could be detected without cytokeratin staining. In addition, cytokeratin-negative cells, which are found in all tumours, can be used as an internal standard for the calculation of ploidy and for quality control (coefficient of variation, linearity) of each individual sample. Cell-cycle analysis revealed significantly higher S-phase and G2M-phase fractions in cytokeratin-gated compared to ungated samples (13.1% versus 10.0% and 8.0% versus 5.4%; P < 0.001). This difference was more pronounced in DNA-diploid than DNA-aneuploid tumours. In conclusion, about 30% of DNA-aneuploid tumours could only be detected after cytokeratin labelling of epithelial cells. Owing to the identification of cytokeratin-positive cells the influence of non-tumoural cell elements on cell-cycle analysis was reduced markedly. Therefore, in cervical cancer, cytokeratin labelling can optimize both the determination of DNA ploidy and cell-cycle analysis. Topics: Cell Cycle; DNA, Neoplasm; Female; Flow Cytometry; Humans; Keratins; Ploidies; Prognosis; Uterine Cervical Neoplasms | 1995 |
Cytokeratin subunit 19 measured by CYFRA 21-1 assay in follow-up of cervical cancer.
The purpose of this study was to evaluate the serum tumor markers CYFRA 21-1 and squamous-cell carcinoma antigen (SCC) in the follow-up of squamous-cell cervical cancer patients. One hundred-ninety-three serum samples, which were collected pretherapeutically and during follow-up of 30 patients suffering from squamous-cell cervical cancer FIGO stage III, were analyzed for SCC and CYFRA 21-1. Cutoff values for SCC and CYFRA 21-1 were 3 and 3.3 micrograms/liter, respectively. Fifteen cases were keratinizing and 15 nonkeratinizing squamous-cell carcinomas. Serum tumor marker results were correlated to the results of the clinical and radiologic examinations. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum SCC and serum CYFRA 21-1 for the whole study group and separately for the keratinizing and nonkeratinizing squamous-cell carcinoma group. Sensitivity, specificity, PPV, and NPV of serum SCC were 66, 91, 93, and 60%, respectively. Serum CYFRA 21-1 showed a sensitivity of 63%, specificity of 96%, PPV of 96%, and NPV of 59%. The combination of SCC and CYFRA 21-1 increased the sensitivity to 78%, with a specificity, PPV, and NPV of 87, 91, and 69%, respectively. In keratinizing squamous-cell carcinoma serum SCC, CYFRA 21-1 and the combination of both had a sensitivity of 76, 64, and 85%, respectively. In nonkeratinizing squamous-cell carcinoma sensitivity was 58, 61, and 72%, respectively. The detection of cervical cancer recurrences with SCC is improved by the combination with CYFRA 21-1. Especially in nonkeratinizing squamous-cell carcinoma CYFRA 21-1 showed promising results. Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Keratins; Neoplasm Recurrence, Local; Predictive Value of Tests; Retrospective Studies; Sensitivity and Specificity; Serpins; Uterine Cervical Neoplasms | 1995 |
Prevention of carcinoma in situ of human papillomavirus type 16-immortalized human endocervical cells by retinoic acid in organotypic raft culture.
To determine the effect of retinoic acid on the development of severe dysplasia or carcinoma in situ from endocervical cells containing human papillomavirus (HPV) type 16.. Two independent lines of HPV 16-immortalized endocervical cells were reconstructed into two squamous epithelial tissues using the organotypic raft culture system to examine the differentiated phenotype. The effect of retinoic acid on dysplastic morphology of differentiation of the epithelia was examined by light microscopy of stained sections and electron microscopy. The endocervical cell type cytokeratin expression pattern was determined by indirect immunofluorescence using specific monoclonal antibodies. Ribonucleic acid expression of the HPV 16 E7 oncogene was examined by in situ hybridization.. Untreated HPV 16-immortalized endocervical cells were reconstructed into squamous dysplastic lesions resembling carcinoma in situ observed in women. Retinoic acid-treated rafts formed epithelia composed of two to three cell layers of columnar-like cells resembling simple epithelium of the endocervix. Electron microscopy and cytokeratin expression patterns confirmed the histology of a differentiated endocervical phenotype after treatment with retinoic acid. Expression of HPV 16 E7 was modestly lower in treated epithelia, preferentially in basal cells.. Retinoic acid prevents the histology and cytokeratin differentiation markers of carcinoma in situ of HPV 16-immortalized endocervical cells. Because the epithelia closely mimic HPV 16-containing severe dysplasias and native endocervical epithelium in women, this immortalized endocervical cell-raft system may be useful as a model to assess the efficacy of agents such as retinoic acid for preventing progression of these lesions to malignant cervical carcinoma. Topics: Carcinoma in Situ; Cell Line, Transformed; Cell Transformation, Neoplastic; Cells, Cultured; Cervix Uteri; Female; Humans; Keratins; Microscopy, Electron; Papillomaviridae; Tretinoin; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1995 |
Cytokeratin fragment 21-1 in gynecologic malignancy: comparison with cancer antigen 125 and squamous cell carcinoma-related antigen.
We measured serum cytokeratin fragment 21-1 (CYFRA 21-1) levels by a solid-phase immunoradiometric assay in 102 healthy Japanese women, and set the reference value at 1.9 ng/ml (mean +2 SD of the serum levels based on a linear distribution). Pretreatment serum CYFRA 21-1 levels were also analyzed in 235 women with benign (n = 94) or malignant (n = 141) gynecologic disease, and were compared with the serum levels of CA 125 and SCC. The respective positivity rates for CYFRA 21-1 and CA 125 were 64.0 and 77.2% in ovarian malignancy, while they were 4.2 and 30.8% in benign ovarian masses. CYFRA 21-1 had an accuracy of 61.3% in diagnosing ovarian malignancy, which was higher than that of CA 125 (53.4%). The positive predictive value of CYFRA 21-1 for ovarian malignancy reached 94.1%, which was significantly (p < 0.005) higher than that of CA 125 (68.8%). These findings indicate the potential usefulness of CYFRA 21-1 as a tumor marker for ovarian malignancy. In addition, the positivity rates fo CYFRA 21-1 in cervical cancer (51.2%) and endometrial cancer (52.2%) were also similar to the respective rates for SCC and CA 125, which suggests that CYFRA 21-1 seems to be a general tumor marker for gynecologic malignancy. Topics: Adolescent; Adult; Biomarkers, Tumor; CA-125 Antigen; Cysts; Endometrial Neoplasms; Female; Genital Neoplasms, Female; Humans; Immunoradiometric Assay; Keratins; Middle Aged; Ovarian Diseases; Ovarian Neoplasms; Reference Values; Uterine Cervical Neoplasms; Uterine Diseases; Uterine Neoplasms | 1995 |
Recognition of atypical reserve cell hyperplasia in cervical smears and its diagnostic significance.
In this study, the histological, cytological, and electron microscopical features of cervical atypical reserve cell hyperplasia are presented. The most important feature of atypical reserve cells in smears is the absence of cytoplasm. Thus, they must be recognized on the absence and not on the presence of a feature, which makes identifying these cells a controversial issue. These stripped nuclei are erroneously believed to be degenerated cylindrical cells, and accordingly are ignored. The atypical reserve cell nuclei are easily damaged in the smear process; however, the MIB-1 staining shows that these disrupted nuclei are derived from proliferating cells. In a follow-up histological study of cases diagnosed as mild dysplasia in a smear, it was found that the presence of MIB-1 positive staining atypical reserve cells was closely related to the development of carcinoma in situ. Recognizing the atypical reserve cells and observing their proliferating activity in a smear might prove to be more important than focusing on the better-known dysplastic cells. Topics: Antibodies, Monoclonal; Biomarkers; Carcinoma in Situ; Cervix Uteri; Female; Humans; Hyperplasia; Keratins; Ki-67 Antigen; Neoplasm Proteins; Nuclear Proteins; Precancerous Conditions; Uterine Cervical Neoplasms; Vaginal Smears | 1995 |
Clinical value of pretreatment serum Cyfra 21-1, tissue polypeptide antigen, and squamous cell carcinoma antigen levels in patients with cervical cancer.
The clinical value of pretreatment serum concentrations of cytokeratin 19 fragments, measured by Cyfra 21-1, was compared with tissue polypeptide antigen (TPA) and squamous cell carcinoma antigen (SCC-Ag) in 78 patients with squamous cell cervical cancer.. Serum levels were compared with tumor stage, size, lymph node status, parametrial involvement, and prognostic data. The clinical performance of the different tests was evaluated by their receiver operating characteristic (ROC) curves.. Serum levels of all markers were related significantly to tumor stage and size. Elevated serum levels of these markers were not found to be predictive for the presence of lymph node metastases. In contrast, a positive relation was found between quantitative serum Cyfra 21-1, TPA, and SCC-Ag levels and the presence of either lymph node metastases or parametrial involvement (i.e., extracervical disease). An elevated, i.e. positive, serum Cyfra 21-1 level was related significantly to the presence of extracervical disease (P = 0.020). The clinical performance of each serum marker in predicting lymph node metastases or parametrial involvement appeared to be similar as expressed by their ROC curves. In the univariate analysis, Cyfra 21-1, TPA, and SCC-Ag showed prognostic value with respect to disease free interval and survival. Elevated serum levels were associated with a poor prognosis. However, after adjusting for tumor stage and size, none of these markers remained statistically significant.. Cyfra 21-1 may be of additional value in assessing stage of disease, tumor size, and the presence of extracervical disease in patients with cervical cancer. Determining its value during follow-up warrants further study. Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Female; Humans; Immunoenzyme Techniques; Immunoradiometric Assay; Keratins; Lymphatic Metastasis; Middle Aged; Peptides; Prognosis; ROC Curve; Sensitivity and Specificity; Serpins; Survival Rate; Tissue Polypeptide Antigen; Uterine Cervical Neoplasms | 1995 |
Human papillomavirus 18-immortalized endocervical cells with in vitro cytokeratin expression characteristics of adenocarcinoma.
To determine whether human papillomavirus (HPV) 18 has a role in the development of adenocarcinoma from human endo- or ectocervical cells.. Secondary cultures of human endo- and ectocervical cells were assayed for immortalization by HPV 18 DNA using lipofection. The effects of immortalization on the patterns of cytokeratin expression were determined by indirect immunofluorescence using monoclonal antibodies. The differentiation phenotype of the immortalized cells was investigated by a modified in vivo implantation system.. Both endo- and ectocervical cells were immortalized by HPV 18. The immortalized cells contained integrated HPV 18 DNA and expressed E6-E7 RNA. The immortalized endocervical cells had a cytokeratin phenotype characteristic of adenocarcinoma, whereas the immortalized ectocervical cells retained a distinct cytokeratin expression pattern of normal parental cells. In an in vivo implantation system, endocervical cells formed a lesion resembling severe dysplasia or carcinoma in situ, whereas ectocervical cells developed into a lesion resembling mild dysplasia. Both cell lines were nontumorigenic in nude mice.. Both endo- and ectocervical cells are targets for immortalization by HPV 18. Based on cytokeratin expression patterns, immortalized endocervical cells, but not ectocervical cells, may be useful as a model for premalignant lesions that progress into adenocarcinoma. Topics: Adenocarcinoma; Animals; Blotting, Northern; Blotting, Southern; Cell Line, Transformed; Cell Transformation, Viral; Cervix Uteri; DNA, Viral; Female; Fluorescent Antibody Technique; Gene Expression; Humans; Keratins; Mice; Mice, Nude; Papillomaviridae; Phenotype; Tumor Cells, Cultured; Uterine Cervical Neoplasms | 1994 |
Human papillomavirus type 18 E6* mRNA in primary tumors and pelvic lymph nodes of Hungarian patients with squamous cervical cancer.
Seven biopsy specimens from squamous-cell carcinomas of the uterine cervix were examined by RT-PCR for human-papilloma-virus(HPV)-specific transcripts. With our HPV18-transcription-specific primer pair (5' nts 127-149; 3' nts 587-607), all 7 were shown to contain one strong viral mRNA signal from the early 6/early 7 open reading frames (E6/E7 ORFs). Sequence analysis of the cloned PCR product proved that the transcript was generated by splicing out an intron in E6 from nucleotides 233 to 416, thereby corresponding to the HPV18 E6* spliced mRNA. Nine out of 9 metastatic and 5 of 7 histologically negative lymph nodes from the same patients were also found to be positive for the same mRNA transcript. However, 4 HPV18 unrelated primary tumors and the connected regional pelvic lymph nodes (3 metastatic, 7 histologically negative) were negative for the HPV18 E6* mRNA. Cytokeratin signals indicating tumor cells of epithelial origin were detected in 7 out of the 9 transcript-positive lymph nodes with histological signs of metastasis and in 2 out of the 5 transcript-positive histologically negative lymph nodes. This suggests that the dispersion of the epithelial monoclonal tumor cells was lymphogenic in origin. Topics: Adult; Base Sequence; Carcinoma, Squamous Cell; DNA Primers; DNA, Neoplasm; DNA, Viral; Female; Gene Amplification; Genes, Viral; Globins; Humans; Hysterectomy; Keratins; Lymph Nodes; Middle Aged; Molecular Sequence Data; Neoplasm Staging; Papillomaviridae; Pelvis; Polymerase Chain Reaction; RNA, Messenger; RNA, Viral; Transcription, Genetic; Uterine Cervical Neoplasms | 1994 |
Invasive squamous cell carcinoma and cervical intraepithelial neoplasia III of uterine cervix. Morphologic differences other than stromal invasion.
The authors compared 69 cases of surgically proven invasive squamous cell carcinoma (ISCC) of uterine cervix with 48 cone biopsy specimens that showed cervical intraepithelial neoplasia (CIN) grade III. Histologic features that were preferentially associated with ISCC included the following: giant bizarre cells (66.7% in ISCC, 6.26% in CIN III, P < .01); large keratinized cells (87% in ISCC, 0% in CIN III, P < .01); keratin pearls (40.6% in ISCC, 0% in CIN III, P < .01); necrosis (79.7% in ISCC, 8.3% in CIN III, P < .01); and neovascularization (56.5% in ISCC, 0% in CIN III). In 51 (74%) cases of ISCC, a CIN III component was present, of which 18 (35.3%) showed large keratinized cells or keratin pearls in the in situ components. None of the CIN III cases showed more than one of the above features. In the ISCC group, the above features occurred with similar frequency in microinvasive and frankly invasive tumors. The authors' results agree with previous Papanicolaou-smear cytologic studies, which found that ISCC can be distinguished accurately from CIN III by the morphology of the neoplasm. The authors concluded that cervical biopsy specimens that show two or more of the above features are highly suggestive of ISCC, even when stromal tissue is absent or insufficient for the assessment of invasion. Furthermore, in cervical biopsy specimens showing CIN III, the presence of large keratinized cells or keratin pearls may signify the presence of invasive lesions elsewhere in the cervical mucosa. Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Giant Cells; Humans; Keratins; Middle Aged; Necrosis; Neoplasm Invasiveness; Neoplasm Staging; Neovascularization, Pathologic; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1994 |
Human uterine cervical epithelial cells grown on permeable support--a new model for the study of differentiation.
The purpose of the present study was to establish culture conditions for human uterine cervical epithelial cells on permeable support and to determine how it affects cervical cell differentiation. Human ectocervical epithelial cells (hECE), HPV-16 immortalized hECE cells (ECE16-1) and Caski cells were grown on collagen-coated filters. Culture conditions, density of cells in culture and expression of epithelial and cervical-cell phenotypic markers were determined and compared in cells grown on filter and on solid support. Compared with the latter, cultures on filter had a higher cell density, hECE cells stratified to 5-12 cell layers compared to 1-3 on solid support, and cells of all three types expressed intercellular tight junctions. The cytokeratin profiles revealed differences between the three cell types as well as differences within the same cell species when grown on filter, compared to solid support. Of particular importance was the finding of a higher expression of K-13 in hECE grown on filter compared to solid support; K-13 is a marker of ectocervical cell differentiation. The cytokeratin profiles of the cultured hECE, ECE16-1 and Caski cells resembled those of ectocervical, squamous metaplastic and endocervical epithelia, respectively. hECE and ECE16-1 expressed involucrin protein, the level of which in both was higher in cells grown on filter compared to solid support. Polarization of the cultures was determined by morphology (stratification of hECE cells, expression of pseudomicrovilli in the apical cell membrane), selective apical vs. basolateral secretion of [35S]methionine- and [35S]cysteine-, [3H]fucose- and [14C]glucosamine-labeled molecules, and positive short-circuit current (Isc) under voltage-clamp conditions. Confluency of the cultures was determined by measuring transepithelial unidirectional fluxes of inert molecules with different molecular weights (MWs) through the paracellular pathway, and by measuring transepithelial conductance. The results indicated transepithelial permeability of 7-22.10(-6) cm.sec-1, which was 5-100 fold smaller compared to blank inserts, with a cut-off MW of 40-70 kDa for hECE and Caski cells. Transepithelial conductance ranged 18.5 to 51.5 mS.cm-2, indicating a leaky but confluent epithelia. Collectively the results indicate the epithelial nature of the cells and their improved differentiation when grown on filter support; hECE is a model for ectocervical epithelium while ECE16-1 and Caski express phenoty Topics: Carcinoma, Squamous Cell; Cell Differentiation; Cell Line, Transformed; Cell Polarity; Cells, Cultured; Ceramics; Cervix Uteri; Collagen; Culture Techniques; Epithelial Cells; Epithelium; Female; Humans; Hydrocortisone; Keratins; Permeability; Polytetrafluoroethylene; Protein Precursors; Tretinoin; Tumor Cells, Cultured; Uterine Cervical Neoplasms; Vimentin | 1994 |
Tumor marker studies of cervical smears: an immunohistochemical approach.
Immunoreactivity with monoclonal antibodies against epithelial membrane antigen (EMA), vimentin, squamous epithelium-specific keratin, nonsquamous epithelium-specific keratin, and polyclonal antibodies epithelial cells of 55 cervical smears using the avidin-biotin-peroxidase complex and indirect immunoperoxidase methods to detect antigens. Most of the abnormal squamous cells with few normal cells were reactive for EMA but the intensity of the reaction was variable in both cases. There was no correlation in the reactivity between normal and abnormal cells with different cytokeratins varying in their molecular weight. Vimentin was also reactive with both cells. The results of this experiment suggest that antibodies used, appear to be of limited usefulness in the diagnosis of cervical smears. Topics: Biomarkers, Tumor; Female; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mucin-1; Mucins; Sensitivity and Specificity; Uterine Cervical Neoplasms; Vaginal Smears; Vimentin | 1994 |
Expression of cytokeratin 10, 13, and involucrin as prognostic factors in low stage squamous cell carcinoma of the uterine cervix.
The identification of pretreatment markers with predictive significance for the presence of lymph node metastases and treatment outcome in low stage cancer of the uterine cervix is clinically important. Because the presence of differentiation-related markers varies in this type of cancer, the authors investigated whether loss of these markers is related to a poor clinical course.. An indirect immunoperoxidase technique was applied to formalin fixed, paraffin embedded tissue sections of 80 patients with International Federation of Gynecology and Obstetrics Stage IB and IIA primary squamous cell cervical carcinomas for detection of expression of cytokeratin 10 and 13, and involucrin. Comparisons were made of the expression of each of these markers among 40 patients with regional node metastases and 40 age-matched patients with no lymph node metastases. Differences in the frequency of expression of these markers also were analyzed in relation to histopathologic characteristics, recurrence, and survival.. Expression of cytokeratin 10, 13, and involucrin was found in 24, 64, and 53%, respectively, of all patients studied. The authors found no differences between patients with positive regional lymph nodes and those with negative lymph nodes. Expression of cytokeratin 13 and involucrin was associated with tumor grade (P = 0.01). No relationship was found between expression of the markers used and recurrence or survival in the entire group. Within the lymph node-positive group, however, the survival rate of patients with tumors with cytokeratin 13 expression was significantly higher than that of patients with tumors lacking cytokeratin 13 expression (P = 0.02).. Expression of cytokeratin 10, 13, or involucrin in the primary tumor is of no predictive value with respect to the presence of regional lymph node metastases in low stage squamous cell cervical cancer. However, cytokeratin 13 expression appears to be of prognostic significance in patients with positive regional lymph nodes. Topics: Adult; Aged; Antibodies, Monoclonal; Biomarkers; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Prognosis; Protein Precursors; Retrospective Studies; Uterine Cervical Neoplasms | 1994 |
Detection of keratin subtypes in routinely processed cervical tissue: implications for tumour classification and the study of cervix cancer aetiology.
We investigated the expression of keratin subtypes 7, 8, 10, 13, 14, 17, 18 and 19 in the normal cervix, in cervical intraepithelial neoplasia (CIN) lesions and in cervical carcinomas, using a selected panel of monoclonal keratin antibodies, reactive with routinely processed, formalin fixed paraffin embedded tissue fragments. The reaction patterns derived for each keratin antibody were compared with known expression patterns of the various epithelia, previously examined in frozen tissues. Although the reactivity of the antibodies was generally acceptable, considerable modifications to the manufacturers' staining instructions were often necessary. For some antibodies, which were previously thought to be reactive with fresh frozen tissue only, we developed staining protocols rendering them reactive with routinely processed material. As with previous findings in frozen sections we observed increasing expression of keratins 7, 8, 17, 18 and 19 with increasing grade of CIN. In cervical carcinomas the differences in keratin detectability between the main categories were more pronounced than in frozen sections, probably due to fixation and processing. For routine pathology, keratin phenotyping of cervical lesions may be of value in classification. The fact that keratin 7 was detected for the first time in reserve cells, and that this keratin was also found to be expressed in a considerable number of CIN lesions and cervical carcinomas supports the suggestion that reserve cells are a common progenitor cell for these lesions. Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Adenosquamous; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; Epithelial Cells; Epithelium; Female; Histological Techniques; Humans; Immunoenzyme Techniques; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1994 |
Cellular and hormonal mechanisms associated with malignant bone resorption.
To obtain a better understanding of the cellular and hormonal mechanisms responsible for the malignant bone resorption associated with metastatic carcinoma, we sought to identify whether tumor cells or tumor infiltrating macrophages were capable of lacunar bone resorption.. Tumor cells and tumor-infiltrating macrophages (TIMS), (nonspecific esterase and F4/80 positive: cytokeratin and tartrate-resistant acid phosphatase and calcitonin response negative), were isolated from carcinomas that developed after subcutaneous implantation of human breast, colon, and cervical carcinoma cell lines into MFI athymic nude mice. These cells were cultured alone or with stromal cells on bone slices and evidence of lacunar resorption sought by scanning electron microscopy.. After 7 to 14 days in co-culture with UMR106 osteoblast-like cells in the presence of 1,25-dihydroxy vitamin D3, only cells of the TIM population differentiated into osteoclast-like cells (nonspecific esterase-negative: tartrate-resistant acid phosphatase-positive) capable of extensive lacunar bone resorption.. Cells within the TIM population but not tumor cells are capable of differentiation into osteoclast-like cells which can resorb bone extensively. Both 1,25 dihydroxyvitamin D3 and bone stromal cells are necessary for this to occur. TIM differentiation into cells capable of lacunar resorption could account for a component of the extensive osteolysis associated with carcinomatous skeletal metastases. Topics: Adenocarcinoma; Animals; Bone Resorption; Breast Neoplasms; Calcitonin; Calcitriol; Carcinoma, Squamous Cell; Cell Differentiation; Cells, Cultured; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Macrophages; Mice; Mice, Nude; Microscopy, Electron, Scanning; Neoplasm Transplantation; Osteoblasts; Osteoclasts; Time Factors; Tumor Cells, Cultured; Uterine Cervical Neoplasms | 1994 |
Prognostic significance of serum fragments of cytokeratin 19 measured by Cyfra 21-1 in cervical cancer.
Pretreatment sera of 78 patients with squamous cell cervical cancer were tested for the presence of cytokeratin 19 (CK 19) fragments to determine the relationship among this parameter, tumor stage, various histopathologic characteristics, and prognosis. For the quantitative determination of CK 19 fragments in serum, the enzyme assay Cyfra 21-1 was used. This assay, based on the simultaneous sandwich principle, utilizes two different monoclonal antibodies. The test was considered positive when levels of Cyfra 21-1 were > or = 1.2 micrograms/liter. Cyfra 21-1 was positive in the majority of patients and in all patients with advanced disease (FIGO III or IVa). A highly significant relationship was found between pretreatment Cyfra 21-1 level and FIGO stage (P < 0.0001). Mean Cyfra 21-1 concentration was elevated in the case of macroinvasive disease (FIGO Ib, IIa, IIb, III, IVa). A distinct relationship was found between tumor size (P < 0.001; r = 0.73) and Cyfra 21-1 level. In the univariate Cox analysis Cyfra 21-1 level was significantly related to both disease-free interval (P < 0.0001) and survival (P < 0.0001) of patients. Patients with an increased Cyfra 21-1 level had a significantly worse prognosis. However, in the stepwise Cox regression analysis, these variables had no additional value over known prognostic factors such as FIGO stage and tumor size. It is concluded that Cyfra 21-1 may be of significance as an additional marker in the management of patients with cervical cancer, but further investigation is needed. Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Humans; Immunoenzyme Techniques; Keratins; Life Tables; Middle Aged; Neoplasm Staging; Peptide Fragments; Prognosis; Proportional Hazards Models; Reagent Kits, Diagnostic; Survival Rate; Uterine Cervical Neoplasms | 1994 |
[Cytokeratin expression in spinocellular carcinoma of the uterine cervix].
Expression of cytokeratins 7, 8, 10, 14, 18 and 19 was studied in 48 cases of advanced (stage II and III) squamous cell carcinomas of the uterine cervix. Despite of the degree of differentiation, the expression of simple epithelia cytokeratins 8 (72.9%) and 19 (97.9%) was high. A subset of eight (16.6%) predominantly poorly differentiated tumours had the expression restricted to simple epithelia pattern (cytokeratin 7 and/or 8 and 18 and/or 19). In twenty cases (41.7%) the cytokeratin 14 was added to this pattern, representing an intermediate differentiation level, while the other twenty tumours, usually exhibiting more pronounced squamous differentiation had the most complete cytokeratin pattern including class 10. This grouping was of no prognostic significance but might represent a valuable tool in the classification of cervical squamous cell carcinoma. Topics: Carcinoma, Squamous Cell; Female; Histocytochemistry; Humans; Keratins; Uterine Cervical Neoplasms | 1994 |
Expression of keratins 1, 6, 15, 16, and 20 in normal cervical epithelium, squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma.
Expression of keratins 1, 6, 15, 16, and 20 was examined in normal cervical epithelia, squamous metaplasia, various grades of cervical intraepithelial neoplasia, and both squamous cell carcinomas and adenocarcinomas of the cervix with monospecific antibodies. Ectocervical epithelium contains all of these keratins except keratin 20. They show a heterogeneous distribution, with a basally restricted detection of keratin 15. Endocervical columnar cells were found to contain significant amounts of keratin 16, whereas the subcolumnar reserve cells expressed considerable amounts of keratin 15 and 16, and frequently keratin 6. These reserve cell keratins were also found in immature and mature squamous metaplastic epithelium. In the cervical intraepithelial neoplastic lesions they were generally found with increasing intensity as the severity of the lesion progressed. In the keratinizing variety of squamous cell carcinoma of the cervix, these three keratins seem to constitute an important part of the intermediate filament cytoskeleton, whereas in nonkeratinizing squamous cell carcinoma, they occur to a much lesser extent. Surprisingly, these keratins were also occasionally found in adenocarcinomas. From these data we conclude that the keratin phenotype of reserve cells and endocervical columnar cells is more complex than previously suggested. In particular, the keratins occurring in reserve cells are also present in most of the premalignant and in a considerable number of the malignant lesions of the cervix. The differentiation features of the various carcinoma types are, however, reflected in their specific keratin filament composition. Topics: Adenocarcinoma; Carcinoma; Carcinoma, Squamous Cell; Cervix Uteri; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Reference Values; Uterine Cervical Neoplasms | 1993 |
Retinoid status controls the appearance of reserve cells and keratin expression in mouse cervical epithelium.
We describe an animal model to induce the histogenesis of squamous metaplasia of the cervical columnar epithelium, a condition usually preceding cervical neoplasia. This model is based on dietary retinoid depletion in female mice. Control sibling mice fed the same diet but with all-trans-retinoic acid (at 3 micrograms/g diet) showed the normal endocervical epithelial and glandular columnar morphology, typical of a simple epithelium without subcolumnar reserve cells. The stratified squamous ectocervical epithelium of these mice fed all-trans retinoic acid showed intense immunohistochemical staining in basal and suprabasal cells with mono-specific antibodies against keratins K5, K14, K6, K13, and, suprabasally, with antibodies specific for K1 and K10. At the squamocolumnar junction, the adjacent columnar epithelium (termed "suprajunctional") did not show staining for K5, K14, K6, K13, K1, and K10 but specifically stained for keratin K8, typical of simple epithelia and absent from the adjacent ectocervical squamous stratified lining (termed "subjunctional"), in striking contrast. Sections of the squamocolumnar junction from mice kept on the vitamin A-deficient diet for 10 weeks showed suprajunctional isolated patches of reserve cells, proximal and distal to the junction. These cells were detected prior to any symptoms of vitamin A deficiency, such as loss of body weight or respiratory discomfort. The subcolumnar reserve cells induced by vitamin A deficiency displayed positive staining for K5 and K14. As deficiency became severe, the reserve cells occupied the entirety of the suprajunctional basement membrane. This epithelium eventually became stratified and squamous metaplastic, the squamocolumnar junction was no longer discernible, and the entire endocervical epithelium and the endometrial glands lost K8 positivity, while acquiring K5, K14, K6, K13, K1, and K10 keratins typical of the ectocervix under normal conditions of vitamin A nutriture. Vitamin A deficiency also altered keratin expression and localization in squamous subjunctional epithelium. In situ hybridization studies for K1 and K5 mRNA showed their major site of expression at the basal (K5) and immediately suprabasal (K1) cell layers. The localization of both K5 and K1 proteins in these same cell layers, and above, is consistent with transcriptional regulation of these keratins. Early vitamin A deficiency caused the appearance of single subcolumnar reserve cells expressing K5 mRNA. After these ce Topics: Animals; Carcinoma, Squamous Cell; Cervix Uteri; Diet; Disease Models, Animal; Epithelium; Female; Immunohistochemistry; In Situ Hybridization; Keratins; Metaplasia; Mice; Mice, Inbred BALB C; Mice, Nude; Phenotype; Precancerous Conditions; Retinoids; RNA, Messenger; Tretinoin; Uterine Cervical Neoplasms; Vitamin A Deficiency | 1993 |
Mesonephric adenocarcinoma of the uterine cervix with focal endocrine cell differentiation.
A case of cervical adenocarcinoma arising in diffuse mesonephric hyperplasia is presented. The hyperplastic and neoplastic tubules showed focal endocrine cell differentiation. Endocrine cells stained with the Grimelius technique, and were immunoreactive for chromogranin and serotonin. Antisera to additional specific hormones were negative. The natural history of this rare tumor is uncertain; the patient presented in this report is free of disease at 10-year follow-up. Topics: Adult; Cell Differentiation; Cervix Uteri; Chromogranins; Female; Humans; Hysterectomy; Immunoenzyme Techniques; Keratins; Mesonephroma; Serotonin; Staining and Labeling; Uterine Cervical Neoplasms; Uterus; Vimentin | 1993 |
Immunohistochemical studies of the uterine cervix after CO2 laser conization.
To investigate the process of the maturation of cervical epithelium after CO2 laser conization.. Specimens from the uterine cervix (248) resected from 31 premenopausal females who had hysterectomy after CO2 laser conization were studied with 2 kinds of anti-keratin monoclonal antibodies (PKK-1, KL-1).. (i) The epithelium covered stroma after 4-6 weeks. (ii) In the normal S-C junction, KL-1 was localized to the middle and upper layers, and PKK-1 to the basal layer. (iii) The staining patterns of KL-1 and PKK-1 in the S-C junctions after conization could be classified into 4 groups according to localization and staining intensity. (iv) The S-C junction appeared normal in all specimens 7 weeks after conization.. The regenerating epithelium covered the stroma within 4-6 weeks, but resolution of squamous epithelial metaplasia only occurred 7 weeks after conization. Topics: Adult; Cell Differentiation; Cervix Uteri; Diagnosis, Differential; Epithelium; Female; Humans; Keratins; Laser Therapy; Time Factors; Uterine Cervical Neoplasms; Vaginal Smears; Wound Healing | 1993 |
Prognostic factors in invasive cervical carcinomas associated with human papillomavirus (HPV). Quantitative data and cytokeratin expression.
As a part of a larger programme to search for the prognostic factors in cervical cancer, quantitative morphometry, demonstration of AgNORs and expression of different cytokeratin polypeptides (SK2-27, SK1, A 53-B/A2) were used to study a series of 85 cervical squamous cell carcinomas, previously analysed for the presence of human papillomavirus (HPV) DNA by in situ hybridization and polymerase chain reaction (PCR). The following nuclear profile parameters were calculated: nuclear area, perimeter, maximum diameter, ellipsoidity (form Ell), regularity (form Ar) and roundness (form Pe). In each case, the number of small (< 3 microns), large (> 3 microns), the total number and the ratio large/small AgNORs were registered. The cancer cell density and the lymphoid cell density were assessed. In the survival analysis, neither the expression of different cytokeratin polypeptides or the pattern of cytokeratin staining proved to be an independent variable. Similarly, none of the nuclear profile parameters analysed possessed an independent prognostic value in the survival analysis. The ratio of large/small AgNORs proved to be a significant independent prognostic predictor (p = 0.0104), second only to the lymphoid cell density. Also the total number of AgNORs was a prognostic indicator. This suggests that AgNOR size and ratio reflect tumor proliferation also in cervical squamous cell carcinoma, as shown in other human malignancies. Similarly, the density of cancer cell nuclei proved to be an independent prognostic predictor (p = 0.0601) in that the tumours in patients with longer survival showed lower density of the nuclei.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Neoplasm Invasiveness; Nucleolus Organizer Region; Papillomaviridae; Polymerase Chain Reaction; Prognosis; Reproducibility of Results; Retrospective Studies; Silver Staining; Uterine Cervical Neoplasms | 1992 |
[The expression of cytokeratin No. 17 in squamous cell cancer of the cervix uteri: an immunohistochemical study of 19 cases].
Monoclonal antibodies E3 against cytokeratin No. 17 were used for immunohistochemical examination of samples from 19 squamous-cell carcinomas of the uterine cervix and 10 cases of squamous-cell metaplasia of the endocervix. The above antibodies selectively labelled reserve cells of the cervical canal mucosa, basal layer of mature metaplastic epithelium and parabasal and basal cells of immature metaplastic squamous epithelium. In large-cell keratinizing, non-keratinizing and small-cell carcinomas, the expression of cytokeratin No. 17 revealed tendency to basal orientation and was in many respects similar to that in metaplastic squamous epithelium. It was suggested that all the squamous-cell carcinomas studied originated from reserve (metaplastic) cells. Topics: Adult; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Middle Aged; Molecular Weight; Uterine Cervical Neoplasms | 1992 |
[Immunohistochemical study on keratin of squamous cell carcinoma of the uterine cervix].
An immunohistochemical study of squamous metaplasia (n = 10), dysplasia (n = 18), squamous cell carcinoma (n = 48) and 3 cases of adenosquamous carcinoma of the uterine cervix with anti-56KD keratin and 68KD keratin antibodies was performed. In the cases of squamous metaplasia, there were two types of staining of which one type had 56KD positive and 68KD negative and another type had both positive. In the cases of dysplasia, there were two types of staining the same as in squamous metaplasia. But in the cases of carcinoma in situ (CIS) (n = 25), there were three types of staining of which the first type had both 56KD and 68KD negative (n = 7), the second type had 56KD positive and 68KD negative (n = 15), and the third type had both 56KD and 68KD positive (n = 3). In invasive carcinoma (n = 23), there were two types of staining the same as in dysplasia of which one type had 56KD positive and 68KD negative (n = 17) and another type had both positive (n = 6). The keratin negative cases in CIS showed morphologically atypical reserve cell hyperplasia composed of atypical small cells with round nuclei and had a small lesion compared with other types. This result suggested that keratin negative CIS was an early form of CIS which was keratin positive. The results indicating that all dysplasia had 56KD keratin positive and CIS had not always 56KD keratin positive suggested that dysplasia was not always a precursor lesion of CIS.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cervix Uteri; Female; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Metaplasia; Molecular Weight; Neoplasms, Multiple Primary; Uterine Cervical Neoplasms | 1992 |
Basal-cell keratins in cervical reserve cells and a comparison to their expression in cervical intraepithelial neoplasia.
Expression of keratins 5, 14 and 17 in endocervical subcolumnar reserve cells was detected by means of immunohistochemical studies using polypeptide specific monoclonal antibodies. These particular keratins that were found among others in basal cells could also be detected to a variable extent in metaplastic and dysplastic cervical lesions. In some cases of immature squamous metaplasia all three keratin subtypes were expressed throughout the full thickness of the epithelium. In contrast, in mature squamous metaplasia a compartmentalization of these keratins was observed. Mature squamous metaplastic epithelium showed a keratin distribution pattern comparable to ectocervical squamous epithelium, with the exception of keratin 17, which was only sporadically found in the basal layer of ectocervical epithelium and was always present in the basal cells of mature squamous metaplastic epithelium. During progression of cervical intraepithelial neoplasia a clear increase in the expression of keratin 17 was observed. However, also keratins 5 and 14 were expressed. Our results demonstrate that a considerable number of premalignant lesions of the uterine cervix express the same keratins as found in the progenitor reserve cells. Lesions that lack expression of keratin 17 may form a distinct group, which are regressive in nature and do not progress into cervical cancer. Topics: Cervix Uteri; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Neoplasm Staging; Uterine Cervical Neoplasms | 1992 |
The solid variant of adenoid cystic carcinoma of the cervix.
We studied seven examples of the solid variant of adenoid cystic carcinoma of the uterine cervix in postmenopausal women who presented with vaginal bleeding and a large ulcerated or polypoid cervical mass. The tumors lacked the characteristic cribriform pattern of conventional adenoid cystic carcinoma. The neoplastic cells were small, undifferentiated, or basaloid and grew in cords, nests, trabeculae, and nodules. Foci of squamous cell carcinoma were seen in three tumors and areas of necrosis in four. A characteristic feature was the production of abundant periodic acid-Schiff's procedure (PAS)-positive basement membrane material that was immunoreactive for collagen IV and that in some areas compressed tumor cells. Electron microscopy on three cases showed globules and cylinders of redundant basal lamina. The tumor cells were joined by desmosomes and contained bundles of tonofilaments. Material similar to basement membrane material appeared to be intracytoplasmic in two tumors. No neurosecretory granules or myoepithelial cells were found. Four deaths were tumor related. Two patients are currently alive, but with local recurrence or metastases; another is alive and well 19 months after surgery. We believe that the solid variant of adenoid cystic carcinoma of the cervix is a distinctive neoplasm that should be separated from small cell carcinomas with or without endocrine features, adenoid basal cell carcinoma, and squamous cell carcinoma. Topics: Aged; Basement Membrane; Carcinoma, Adenoid Cystic; Cell Nucleus; Collagen; Cytoplasm; Female; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mucin-1; Necrosis; Staining and Labeling; Uterine Cervical Neoplasms | 1992 |
Patterns of keratin subsets in normal and abnormal uterine cervical tissues. An immunohistochemical study.
We investigated the use of three monoclonal antikeratin antibodies on routinely formalin-fixed and paraffin-embedded punch and cone biopsies of the normal human uterine cervix and its metaplastic and premalignant lesions. Monoclonal antibodies used were AE8, which is specific for keratin 13; 34BE12, which reacts with keratins of the stratified squamous epithelium; and CAM5.2, which is specific for keratin 8. All these antibodies performed well in routinely processed surgical pathology material. AE8 antibody stained the suprabasal layer of the normal squamous epithelium. Squamous metaplasia and dysplasia were stained in 50% of the cases. Normal suprabasal distribution of the keratin 13, however, was lost in all positive dysplasia cases. CAM5.2 reacted with normal columnar cells in all cases, and squamous metaplasia was focally positive in 20% of the cases. Dysplasia showed a positive reaction in 30% to 40% of the cases. The 34BE12 antibody was reacting with the full thickness of the squamous epithelium. Squamous metaplasia and dysplasia were positive in 80% of the cases. In addition, 34BE12 stained reserve cell hyperplasia, making it a useful marker for this condition. Our results demonstrate that keratin immunohistochemistry with the above-listed antibodies gives pathogenetically interesting information on cervical lesions. Topics: Antibodies, Monoclonal; Carcinoma in Situ; Cervix Uteri; Condylomata Acuminata; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Uterine Cervical Diseases; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1992 |
Acantholytic squamous cell carcinoma of the uterine cervix with amyloid deposition.
An 84-year-old woman suffered for 1 year from intermittent vaginal bleeding. Clinical examination revealed a large ulcerative cervical tumor that was histologically classified as well-differentiated squamous cell carcinoma. Acantholytic areas, apoptotic cell death, and pronounced amyloid deposition characterized the tumor. No evidence of papilloma virus infection was found in immunohistochemical examination or in nucleic acid in situ hybridization. Amyloid formed globular structures surrounded by neoplastic cells that reacted with cytokeratin antibodies. Although the amyloid itself was not labeled, electron microscopy showed filamentous degeneration of the squamous cells analogous to that described in different types of cutaneous keratin-derived amyloidoses. It was concluded that similar pathogenetic mechanisms are involved both in the cutaneous amyloidosis and in the amyloid deposition of squamous cell carcinoma. Topics: Aged; Aged, 80 and over; Amyloid; Carcinoma, Squamous Cell; Female; Humans; Keratins; Microscopy, Electron; Plasma Cells; Uterine Cervical Neoplasms | 1992 |
[Immunohistologic characterization of skin metastases in a patient with simultaneous cancers of the rectum and cervix].
A patient with skin metastases several years after surgical treatment of carcinoma of the cervix and the rectum is presented. Comparative histology and immunohistochemical analysis with anti-cytokeratin antibodies implicated the carcinoma of the cervix as the source of the skin infiltrates. Based on this patient's case record, the use of anti-cytokeratin antibodies for identification and subtyping of epithelial or carcinoma cells is discussed with special reference to cytokeratin 7. Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Combined Modality Therapy; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Staging; Neoplasms, Second Primary; Rectal Neoplasms; Skin; Skin Neoplasms; Uterine Cervical Neoplasms | 1992 |
The effect of sodium butyrate on the growth characteristics of human cervix tumour cells.
Sodium butyrate has been shown to affect cell proliferation, and, at concentrations above approximately 0.5 mM, to cause cell death in some tumour cell lines. When combined with cytotoxic drugs increase in chemosensitivity has been observed. We are presently carrying out a study of the combined effects of sodium butyrate and cytotoxic drugs on cultured cervix tumour cells. To provide a baseline for this study we have carried out a systematic investigation of the effects of sodium butyrate alone on the growth characteristics of cervix tumour cells cultured as multicell spheroids. This has shown that concentrations of n-butyrate of 0.005 mM to 0.50 mM decrease cell proliferation without inducing cell death, the effect increasing with increasing concentration. Butyrate concentrations greater than 0.50 mM cause cell death after a period of 5 to 15 days exposure, dependent on concentration. Concentrations of 0.010 mM and above cause fragmentation of, and increased cell shedding from, multicell spheroids, suggesting an effect on the cell surface. Concentrations of butyrate greater than 0.10 mM cause a considerable increase in the synthesis of cytokeratin, as shown by reaction with cytokeratin antibody. Correlated with this is a marked increase in cell size, concentrations of butyrate of 2.0 or 3.0 mM leading to an approximate doubling of cell diameter, followed by cell disintegration. The effects of butyrate less than 0.25 mM are readily reversible. At concentrations greater than 0.25 mM the effects are reversible up to a limit of about 7 to 20 days depending on concentration, even when cytokeratin synthesis has been induced. Topics: Butyrates; Butyric Acid; Cell Cycle; Dose-Response Relationship, Drug; Female; Humans; In Vitro Techniques; Keratins; Ki-67 Antigen; Nuclear Proteins; Tumor Cells, Cultured; Uterine Cervical Neoplasms | 1992 |
Squamous metaplasia of normal and carcinoma in situ of HPV 16-immortalized human endocervical cells.
The importance of cervical squamous metaplasia and human papillomavirus 16 (HPV 16) infection for cervical carcinoma has been well established. Nearly 87% of the intraepithelial neoplasia of the cervix occur in the transformation zone, which is composed of squamous metaplastic cells with unclear origin. HPV DNA, mostly HPV 16, has been found in 90% of cervical carcinomas, but only limited experimental data are available to discern the role of HPV 16 in this tissue specific oncogenesis. We have initiated in vivo studies of cultured endocervical cells as an experimental model system for development of cervical neoplasia. Using a modified in vivo implantation system, cultured normal endocervical epithelial cells formed epithelium resembling squamous metaplasia, whereas those immortalized by HPV 16 developed into lesions resembling carcinoma in situ. In contrast, their ectocervical counterparts formed well differentiated stratified squamous epithelium and a lesion with mild dysplastic change, respectively. The HPV 16-immortalized cells showed in vivo cytokeratin expression patterns similar to their respective normal counterparts, confirming their different origins. Thus, this study provides direct experimental evidence for the transformation of simple epithelial cells of endocervical origin into stratified squamous metaplasia and indicates the differential susceptibility of endo- and ectocervical epithelial cells for conversion to cancer by HPV 16. Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Transformed; Cell Transformation, Neoplastic; Cells, Cultured; Cervix Uteri; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Mice; Mice, Nude; Microscopy, Electron; Mucins; Papillomaviridae; Transplantation, Heterologous; Uterine Cervical Neoplasms | 1992 |
Keratin expression in cervical cancer.
Using a panel of 21 monoclonal and 2 polyclonal keratin antibodies, capable of detecting separately 11 subtypes of their epithelial intermediate filament proteins at the single cell level, we investigated keratin expression in 16 squamous cell carcinomas, 9 adenocarcinomas, and 3 adenosquamous carcinomas of the human uterine cervix. The keratin phenotype of the keratinizing squamous cell carcinoma was found to be most complex comprising keratins 4, 5, 6, 8, 13, 14, 16, 17, 18, 19, and usually keratin 10. The nonkeratinizing variety of the squamous cell carcinoma expressed keratins 6, 14, 17, and 19 in all cases, usually 4, 5, 7, 8, and 18, and sometimes keratins 10, 13, and 16. Adenocarcinomas displayed a less complex keratin expression pattern comprising keratins 7, 8, 17, 18, and 19, while keratin 14 was often present and keratins 4, 5, 10 and 13 were sporadically found in individual cells in a few cases. These keratin phenotypes may be useful in differential diagnostic considerations when distinguishing between keratinizing and nonkeratinizing carcinomas (using keratin 10, 13, and 16 antibodies), and also in the distinction between nonkeratinizing carcinomas and poorly differentiated adenocarcinomas, which do not express keratins 5 and 6. Keratin 17 may also be useful in distinguishing carcinomas of the cervix from those of the colon and also from mesotheliomas. Furthermore the presence of keratin 17 in a CIN I, II, or III lesion may indicate progressive potential while its absence could be indicative of a regressive behavior. Because most carcinomas express keratins 8, 14, 17, 18, and 19, we propose that this expression pattern reflects the origin of cervical cancer from a common progenitor cell, i.e., the endocervical reserve cell that has been shown to express keratins 5, 8, 14, 17, 18, and 19. Topics: Adenocarcinoma; Adult; Aged; Carcinoma; Carcinoma, Squamous Cell; Endometriosis; Female; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Staining and Labeling; Uterine Cervical Neoplasms | 1992 |
Down-regulation of keratin 14 gene expression after v-Ha-ras transfection of human papillomavirus-immortalized human cervical epithelial cells.
Keratin expression in human cervical squamous cell carcinoma (SCC) lines differed significantly from both normal and human papillomavirus (HPV) immortalized exocervical cells. Keratin 14 (K14) expression, determined by protein synthesis and mRNA levels, was dramatically down-regulated in the cervical SCC lines while keratin 5 (K5) expression was not. K14 expression was similarly down-regulated in an HPV-16 immortalized cervical cell line after tumorigenic transformation with recombinant v-Ha-ras DNA. Cultures derived from nude mouse tumor explants also exhibited an altered keratin profile and the levels of K14 protein synthesis, as well as K14 mRNA, were not detectable. In both cases K5 protein synthesis was not significantly down-regulated. In addition, neoplastic cervical SCC lines exhibited up-regulation of keratins 7, 8, 13, and 19, combined with slight down-regulation of keratins 6 and 16. Epidermal keratinocytes responded in a different manner to exocervical cells. Transfection of human papillomavirus-immortalized epidermal keratinocytes with the BglII N fragment of herpes simplex virus 2 produced a neoplastic cell line, but K5 and K14 expression remained unchanged. Thus, neoplastic transformation of human exocervical cells, both in vivo (spontaneous cervical SCC) and in vitro (HPV-16- and v-Ha-ras-induced cervical SCC), is accompanied by characteristic changes in keratin expression. The specific down-regulation of K14 in these tumorigenic cervical cells, in the absence of significant changes in the expression of K5, implies that the normal coordinate regulation of K5 and K14 gene expression has been uncoupled. Topics: Blotting, Northern; Carcinoma, Squamous Cell; Cell Line, Transformed; Cervix Uteri; Down-Regulation; Electrophoresis, Gel, Two-Dimensional; Female; Genes, ras; Humans; Keratins; Papillomaviridae; RNA, Messenger; Transfection; Uterine Cervical Neoplasms; Uterine Neoplasms | 1992 |
Patterns of keratin 19 expression in normal, metaplastic, condylomatous, atrophic, dysplastic, and malignant cervical squamous epithelium.
Keratin 19 (K-19) expression has been strongly correlated with dysplasia in oral epithelium. Expression of K-19 was evaluated by immunoperoxidase staining in formalin-fixed normal ectocervical tissue, normal endocervical tissue, cervical dysplasia, squamous metaplasia, atrophic epithelium, cervical condylomas, and invasive carcinoma to determine if a correlation of K-19 expression with dysplasia was present in the cervical epithelium. Uniform expression of K-19 was seen in endocervical epithelium and in the basal layer of normal ectocervical epithelium in all areas where these epithelia were present. Cervical dysplasia without associated condylomatous changes showed increased expression of K-19 in suprabasal epithelium, corresponding to the level of immature cells. Squamous metaplasia was characterized by scattered cells with increased staining (patch-quilt pattern). There was considerable overlap in the patterns of K-19 expression in dysplastic and metaplastic epithelium. Thus K-19 staining pattern could not be used as a distinctive marker for dysplasia in the cervical epithelium. Atrophic epithelium showed a characteristic uniform but low-level expression of K-19 in suprabasal areas. This pattern may be of diagnostic use in differentiating atrophic lesions from dysplasia. Condylomas showed focal loss of K-19 in the basal layer, suggesting induction of premature differentiation in the basal layer by human papillomavirus infection. Invasive carcinomas showed variable patterns. K-19 is a marker of immature cervical squamous epithelium, with generally distinctive but sometimes overlapping patterns of expression in various diagnostic categories. Topics: Atrophy; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cervix Uteri; Condylomata Acuminata; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Uterine Cervical Diseases; Uterine Cervical Neoplasms | 1992 |
Extinction of the HPV18 upstream regulatory region in cervical carcinoma cells after fusion with non-tumorigenic human keratinocytes under non-selective conditions.
'Universal fuser' clones of a human papillomavirus type 16 positive cervical carcinoma cell line (SiHa) were established to study the effect of a non-tumorigenic fusion partner on the regulation of a stably integrated chloramphenicol acetyltransferase (CAT) gene controlled by the HPV18 upstream regulatory region under non-selective conditions. The CAT expressing cells were fused with both non-tumorigenic, spontaneously immortalized human keratinocytes (HaCaT) and non-modified SiHa cells. The resulting hybrids were characterized by restriction enzyme fragment length polymorphism analysis and flow cytometry. While the non-selectable, HPV18-driven indicator gene is constitutively expressed in SiHa cells, the CAT activity is extinguished in SiHa x HaCaT cells, but still present in SiHa x SiHa hybrids. Examination of the cytokeratin expression pattern reveals that the keratinocyte phenotype seems not only to be dominant in terms of the extinction of the HPV18 regulatory region but also by the conservation of most of the differentiation markers of the non-tumorigenic fusion partner. Cycloheximide treatment and intracellular competition experiments using the transient COS7 fusion-amplification technique are accompanied by the reactivation of the marker gene in previously CAT- SiHa x HaCaT hybrids. These data strongly suggest that trans-acting negative regulatory factors derived from the non-malignant human keratinocytes are responsible for the extinction phenomenon. Topics: Animals; Blotting, Northern; Carcinoma; Cell Fusion; Chlorocebus aethiops; Electrophoresis, Gel, Two-Dimensional; Female; Gene Expression Regulation, Viral; Humans; In Vitro Techniques; Keratinocytes; Keratins; Papillomaviridae; Polymorphism, Restriction Fragment Length; Regulatory Sequences, Nucleic Acid; Repressor Proteins; RNA, Messenger; Transcription, Genetic; Transfection; Uterine Cervical Neoplasms | 1991 |
Immunohistochemical studies on uterine tumors. I. Invasive squamous cell carcinomas of the cervix and their precursors.
40 invasive carcinomas and 80 preinvasive lesions of the uterine cervix were studied immunohistochemically; 40 benign lesions served as controls. On histological and immunohistochemical examination, invasive and preinvasive carcinomas were subdivided in the squamous (large cell, ectocervical) type and the reserve cell (small, large or clear cell, endocervical) type. Immunohistochemically, 100% of the invasive and preinvasive squamous cell carcinomas were positive with anticytokeratins 13, 14, 16 and negative with anticytokeratin 8 and anti-CEA. Most of the invasive and preinvasive reserve cell carcinomas showed a coexpression of cytokeratins 13, 14, 16, 8 and CEA. The subdivision of invasive carcinomas of the ecto- and endocervix into squamous cell and reserve cell types made by means of their structural differences is substantiated and re-evaluated by their immunohistochemical reactions. Both types of carcinomas retain the complex pattern of cytokeratins shown by their cells of origin. The reserve cell carcinomas, in addition, acquire a coexpression for CEA that indicates malignant transformation. The subdivision is of clinical importance because both types of carcinomas vary in their mode and speed of invasion and spread and in their association with HPV infection. Topics: Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Invasiveness; Precancerous Conditions; Uterine Cervical Neoplasms | 1991 |
[Prospective immunohistologic search for metastases using monoclonal anti-cytokeratin antibodies in gynecologic malignancies].
A higher prevalence of positive lymph node metastases can be found with immunohistological methods in comparison with conventional technique. We examined the lymph nodes from 20 patients with gynecological malignant tumors. We found in 304 lymph nodes with conventional technique 3.3% metastases. With immunohistological methods we showed in 9.9% of the lymph nodes metastases. Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Female; Fluorescent Antibody Technique; Genital Neoplasms, Female; Humans; Keratins; Lymph Nodes; Mesonephroma; Neoplasm Staging; Ovarian Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms | 1991 |
Cytokeratin intermediate filament pattern in uterine cervical biopsies.
Twenty-seven uterine cervical biopsies with histological diagnoses ranging from normal through dysplasia to invasive carcinoma were analysed for cytokeratin pattern in two-dimensional gel electrophoresis. No direct correlation between histological diagnosis and cytokeratin pattern was observed. Topics: Adenocarcinoma; Antibodies, Monoclonal; Biopsy; Carcinoma in Situ; Carcinoma, Squamous Cell; Cervix Uteri; Female; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1991 |
Immortalization by human papillomavirus type 16 alters retinoid regulation of human ectocervical epithelial cell differentiation.
Human cervical cells are a primary site of papillomavirus infection and 90% of all cervical tumors are positive for human papillomavirus (HPV) DNA. Over one-half million cases of HPV-associated cervical, vulvar, and penile cancers are reported per year. Yet, in spite of the magnitude of this problem, the effects of HPV infection on cervical cell growth and differentiation are not well characterized. To study these effects we have developed a clonal cell line of HPV-16-immortalized ectocervical epithelial cells, ECE16-1. In the present study we demonstrate that under normal growth conditions the cytokeratin content of ECE16-1 cells is dramatically altered compared to normal cervical cells; the level of K5, K6, K14, K16, and K17 is reduced and the level of K7, K8, and K19 is increased. We demonstrate that this change is largely due to a difference in the response of the cells to retinoids, as growth in retinoid-free medium produces a complete normalization of cytokeratin levels. Upon addition of natural and synthetic retinoids, the levels of cytokeratins K5, K6, K14, K16, and K17 are reduced, while the levels of cytokeratins K19, K7, and K8 are increased. Cytokeratin K13 levels are only slightly altered. The level of involucrin, a precursor of the cervical cell envelope (superficial cell), is not changed by immortalization nor is it regulated by retinoids. Transglutaminase activity is also not appreciably altered by immortalization; however, ECE16-1 cells make fewer envelopes than normal ECE cells. Our results clearly indicate that natural and synthetic retinoids suppress the differentiation of HPV transformed cervical cells. In early, low grade, cervical intraepithelial neoplasia, transcription of the HPV16 E6/E7 oncogenes is confined to the suprabasal layers. Our results suggest that retinoids, because they inhibit the differentiation of HPV16 immortalized cervical cells, may reduce the extent of viral oncogene transcription and thus be useful in slowing the neoplastic process. Topics: Cell Differentiation; Cell Transformation, Viral; Cells, Cultured; Cervix Uteri; Epithelial Cells; Epithelium; Female; Humans; Keratins; Papillomaviridae; Phenotype; Retinoids; RNA, Messenger; Transcription, Genetic; Transfection; Tretinoin; Uterine Cervical Neoplasms; Virus Replication; Vitamin A | 1991 |
Mucinous neoplasm in the cervix associated with a mucinous neoplasm in the ovary and concurrent bilateral sex cord tumors with annular tubules: immunohistochemical study.
The patient described synchronous mucinous tumors of the cervix and ovary and concurrent annular tubules, but without the classical stigmata of Peutz-Jeghers syndrome. The cervical tumor was an invasive mucinous adenocarcinoma with mixed components of minimal deviation and less-well-differentiated endometrioid morphology. The ovarian tumor had the benign appearance of a mucinous adenoma but histologically revealed areas of invasive carcinoma. Immunohistochemical studies of the mucinous neoplasms of the cervix and ovary are discussed. Neither the staining properties of mucin, the pattern of immunostaining for carcinoembryonic antigen, nor any other common markers were helpful in distinguishing the mucinous neoplasms. Positive immunostaining for low-molecular-weight cytokeratin in the filament profile of sex cord tumors with annular tubules was of particular interest since it has not to our knowledge been previously described. Topics: Adenocarcinoma, Mucinous; Adult; Antigens, Neoplasm; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Uterine Cervical Neoplasms | 1991 |
Evaluation of histologic, morphometric, and immunohistochemical criteria in the differential diagnosis of small cell carcinomas of the cervix with particular reference to human papillomavirus types 16 and 18.
Clinicopathologic analyses including immunohistochemical, morphometric, virologic, and DNA ploidy studies were performed on seven cases of small cell (undifferentiated) carcinoma (SCC) and 13 cases of small cell squamous carcinoma (SCSC) of the uterine cervix in an attempt to evaluate which criteria are the most useful in identifying aggressive cervical carcinomas composed of small cells. Highly malignant behavior was found to correlate most closely with the histologic pattern of the tumor. Diffuse infiltration by round to spindle-shaped cells with hyperchromatic nuclei similar to small cell carcinoma in other organs correlated with a high frequency of lymph node metastasis and tumor recurrence. In contrast, tumors with well-defined nests similar to large cell nonkeratinizing squamous cell carcinoma were associated with low rates of lymph node metastasis and recurrence. Although there were trends in the distribution of neuroendocrine and cytokeratin immunohistochemical markers, frequency of detection of HPV 16 and 18 DNA sequences, and ploidy patterns, these features showed considerable overlap and none assisted in consistently separating these two types of neoplasms. Consideration of several features, however, could assist in the differential diagnosis. Women with SCC tended to be younger (mean age 36 yr) compared to women with SCSC (mean age 50 yr). A squamous intraepithelial lesion, i.e., cervical intraepithelial neoplasia, was present in association with 60% of SCSC but was not found in any case of SCC. Tumors positive for keratin and negative for neuroendocrine markers were invariably SCSC, whereas those negative for keratin and positive for neuroendocrine markers were always SCC.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; DNA, Neoplasm; DNA, Viral; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Papillomaviridae; Ploidies; Polymerase Chain Reaction; Uterine Cervical Neoplasms | 1991 |
Cytokeratin intermediate filament pattern and human papillomavirus type in uterine cervical biopsies with different histological diagnosis.
The cytokeratin pattern and the presence of human papillomavirus (HPV) were analyzed in 53 uterine cervical biopsies. The biopsies were histologically characterized and the diagnosis ranged from normal through dysplasia to carcinoma. The cytokeratins were identified by their immunological reactivity with the monoclonal antibodies AE1 and AE3. The tissue was typed for the presence of HPV types 11, 16 and 18. We have previously shown that there was no correlation between the expression of cytokeratins No. 14, 15, 16 and 19 (K14, K15, K16 and K19) and the histological diagnosis of cervical biopsies. The present study shows that the cytokeratin pattern cannot be correlated to HPV infection of the cervical tissue either. Topics: Autoradiography; Carcinoma in Situ; Carcinoma, Squamous Cell; Cervix Uteri; Female; Humans; Immunoblotting; Intermediate Filaments; Keratins; Papillomaviridae; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1991 |
[Tissue repair of uterine cervix--cell-biological properties of normal uterine cervical epithelia of transformation zone in vitro].
The objective of this study is to culture the epithelia of the transformation zone of the uterine cervix for long term and evaluate their biological characteristics, such as morphology, growth behavior, alkaline phosphatase activity and heterotransplantability. The epithelia of transformation zone of 15 cases of myoma uteri were cut into 1 x 1 x 1 mm fragments and placed directly on the cover glass. The explants were cultured at 37 degrees C in 5% CO2 and 95% air. In vitro outgrowth of squamous cells (squamous cell outgrowth pattern) was observed in 44, that of columnar cells (columnar cell outgrowth pattern) was observed 49, a mixture of squamous and columnar cell outgrowth patterns was 52 out of 198 explants of transformation zone. The squamous cells were polygonal in shape and showed a pavement-like cell arrangement. The glandular cells grew in whorled fashion. Along the margins of the outgrowth of glandular cells, two types of cells were seen after 2 weeks of culture. One type contained secretory vacuoles of glandular cell, and the other type contained a large number of tonofilaments of squamous metaplastic cells. These phenomena suggested that biological characteristics of the cells in vivo can well be retained in vitro for a relative long term (about 6 weeks). Topics: Adult; Alkaline Phosphatase; Animals; Cell Division; Cells, Cultured; Cervix Uteri; Epithelial Cells; Epithelium; Female; Genome, Viral; Humans; Karyotyping; Keratins; Mice; Middle Aged; Papillomaviridae; Regeneration; Tissue Plasminogen Activator; Transplantation, Heterologous; Uterine Cervical Neoplasms | 1991 |
Minimal deviation adenocarcinoma (adenoma malignum) of the endocervix: a histochemical and immunohistochemical study of two cases.
The histopathological diagnosis of minimal deviation adenocarcinoma (adenoma malignum) of the endocervix may be difficult. Two cases of minimal deviation adenocarcinoma (MDA) were examined using mucin histochemistry and immunocytochemistry with antibodies to epithelial membrane antigens (HMFG1, Ep1), low-molecular-weight cytokeratins (CAM 5.2), carcinoembryonic antigen (CEA), and alpha-amylase. The results were compared with those for normal endocervical glands. Reactivity for CEA in MDA was focal and would be unreliable for biopsy diagnosis. Both cases of MDA contained abundant neutral mucins and sialomucins, whereas sulfomucins were rarely detected; this pattern contrasted with that of normal endocervix. Neoplastic glandular epithelial cells in MDA consistently showed both luminal and cytoplasmic reactivity with Ep1 and HMFG1, whereas normal cervix showed luminal labeling only. Thus, mucin histochemistry and immunohistochemical detection of epithelial membrane antigens may distinguish between extremely well differentiated neoplastic glands in MDA and normal endocervical glands, and hence may aid diagnosis in biopsy specimens. Topics: Adenocarcinoma; Adult; Amylases; Carcinoembryonic Antigen; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Mucins; Uterine Cervical Neoplasms | 1990 |
Immunohistochemical study of possible changes in keratin expression during neoplastic transformation of the uterine mucosa.
The present study aimed to examine possible changes in keratin expression during neoplastic transformation of the uterine mucosa and possible differences in keratin expression between endocervical and endometrial adenocarcinomas. Routinely processed specimens with normal morphology or neoplastic changes were stained immunohistochemically using 5 commercial antibodies to keratin-filaments of molecular weight 39-58 kD: CAM 5.2, RCK 102, MCA 144, PKE and PRE. We generally found a change in keratin expression during the neoplastic transformation, consisting of pronounced heterogeneity compared with normal epithelia. In distinguishing koilocytic atypia from CIN, RCK 102 (52.5, 58 Kd) may prove helpful as it stains neoplastic cells strongly and shows no reaction in koilocytic. Staining with the antibody CAM 5.2 (reactive with 39, 43, 50 kD filaments) may aid in distinguishing between cervical and endometrial adenocarcinomas. The former is stained uniformly; the latter shows a more variable staining. Topics: Adenocarcinoma; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Mucous Membrane; Neoplasm Invasiveness; Pregnancy; Staining and Labeling; Uterine Cervical Neoplasms; Uterine Neoplasms; Uterus | 1990 |
Changing patterns of keratin expression during progression of cervical intraepithelial neoplasia.
The expression of keratins in normal cervical epithelia, metaplastic epithelium, and cervical intraepithelial neoplasia (CIN) grades I, II, and III is investigated with a panel of keratin polypeptide-specific monoclonal antibodies. This approach allowed the detection of individual keratins 4, 7, 8, 10, 13, 14, 18, and 19 at the single-cell level. By using an antibody recognizing keratins 5 and 8 (RCK 102) and two antibodies specific for keratin 8 (CAM 5.2 and M 20), it was also possible to derive information on the distribution of keratin 5. Our results show that during immature squamous metaplasia there is an acquisition of keratins typical of squamous epithelium, ie, keratins 4, 5, 13, and 14. This process continues during further differentiation to mature squamous metaplasia. In premalignant lesions the expression pattern of the progenitor reserve cells and immature squamous metaplastic epithelium is partly conserved. However, in most cases an induction in the expression of the keratins 4, 13, and 14 was observed. Furthermore, CIN III shows a more extensive expression of keratins typical of simple epithelia, ie, keratins 8 and 18, as compared to CIN I and CIN II. Topics: Adult; Aged; Cervix Uteri; Epithelium; Female; Histocytochemistry; Humans; Keratins; Middle Aged; Uterine Cervical Neoplasms | 1990 |
[Immunohistochemical study of cells of invasive cancer of the vaginal part of the cervix uteri].
Immunohistochemical study of cervical carcinoma used EE21-06d monoclonal antibodies which identify five cytokeratin polypeptides inherent in the squamous epithelium. PAP-method and reaction of immunofluorescence were employed. Initial stages of squamous cell carcinoma invasion were characterized by bleaching or complete cell discoloring of most tumor cells. However, in deeply invading tumors, the share of intensively stained cells was markedly increased. The results point to expression of different cytokeratins or cell clones replacement with tumor progression. The peculiarities of cytokeratin distribution may serve to determine the degree of invasion and differentiation of tumor cells. Topics: Adult; Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Cervix Uteri; Female; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Uterine Cervical Neoplasms | 1990 |
The expression of cytokeratin 19 in cervical neoplasia.
Topics: Carcinoma; Female; Humans; Keratins; Uterine Cervical Neoplasms | 1990 |
The histogenetic origin of cervical mesonephric hyperplasia and mesonephric adenocarcinoma of the uterine cervix studied with immunohistochemical methods.
Forty-four cases of mesonephric hyperplasia (MH) and two adenocarcinomas arising from mesonephric remnants (MA) in the cervix were compared immunohistochemically with 10 embryonic and fetal mesonephric tissues. The mesonephric cells retained their pattern for intermediate filaments during ontogenesis, as well as in the mature, hyperplastic, and neoplastic states: they expressed cytokeratin 8, cytokeratin 13, and vimentin, the two latter in variable amounts. In embryonic mesonephric tissues, cytokeratin was absent, whereas the staining for vimentin was intense. Fetal mesonephric cells stained for cytokeratin 13 and vimentin, but that staining diminished as maturation progressed. All MH and MA expressed cytokeratin 8, whereas only 20-30% of the cells in MH and 10-20% of carcinomatous mesonephric cells showed positive reactions with anti-cytokeratin 13 and anti-vimentin. CEA was always negative in cells of mesonephric origin. We regard these results to be important, since the reactions with anti-CEA and anti-vimentin enable one to distinguish cervical adenocarcinomas of mesonephric origin from those of endocervical origin, the latter being CEA-positive and vimentin-negative. Clinical studies revealed that approximately 75% of the patients with MH had used oral contraceptives for several years, 46% had precancerous lesions of the cervix, and in 62% the cervical mucosa showed adenomatous microglandular hyperplasia. We believe that hyperplasia of mesonephric remnants in the cervix may occur more often in patients with disturbed hormonal balance. However, the lack of a control population does not enable us to advance this hypothesis with assurance. Topics: Adult; Aged; Diagnosis, Differential; Female; Humans; Hyperplasia; Immunohistochemistry; Keratins; Mesonephroma; Mesonephros; Middle Aged; Uterine Cervical Neoplasms; Vimentin | 1990 |
A novel monoclonal antibody against squamous cell carcinoma.
The monoclonal antibody, INS-2, was raised against rat fibroblasts transformed by open reading frames E6 and E7 of human papillomavirus (HPV) DNA. In immunoperoxidase testing of frozen sections, the INS-2 antibody was reactive with all squamous cell carcinomas of the uterine cervix and esophagus tested. In contrast, no antibody binding was detected with adenocarcinomas of various origins. Similarly, normal tissues, lymphoid cells and erythrocytes from multiple donors were negative, except that binding localized at basal cells in normal squamous epithelium was observed. Interestingly, strong staining was observed in dysplastic cells of cervical intraepithelial neoplasia and at the growing edge of squamous cell carcinomas. The antigen for the INS-2 antibody is a non-sialyl glycoprotein with Mw. 40,000 and appears to be a squamous cell-specific cell differentiation marker, although it is not related to HPV-DNA-derived protein. Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Keratins; Mice; Mice, Inbred BALB C; Molecular Weight; Oncogene Proteins, Viral; Papillomavirus E7 Proteins; Rats; Uterine Cervical Neoplasms | 1990 |
Expression of cytokeratin No. 19 polypeptide in genital papillomavirus lesions.
A series of 23 punch biopsies proved to contain human papillomavirus (HPV) type 16 and with established clinical course (including HPV-NCIN, HPV-CIN I, and HPV-CIN II lesion), and 18 additional biopsies of HPV 6-, 11-, 16- or 18-induced genital lesions were analyzed immunohistochemically for expression of cytokeratin No. 19 polypeptide. An immunoperoxidase-ABC technique was used with a polyclonal antibody raised against a synthetic nonapeptide corresponding to the residues 2-10 of the NH2-end, non-alpha-helical region. This polyclonal cytokeratin No. 19 antibody stained mainly (but not exclusively) the basal cells of the normal exocervical epithelium (heterogeneous pattern). Basal cell staining was intense slightly more frequently in HPV-CIN than HPV-NCIN lesions, i.e., ++ or more in 14/24 (58.3%) versus 8/17 (47.0%), respectively. The difference was more marked in the staining of the superficial cells, 70.8 and 58.8% showing intense expression of cytokeratin No. 19, respectively. In 6 (21.4%) of the 28 HPV 16 lesions, basal cell layer was intensely stained, as contrasted to none of the 13 HPV 6, 11 or 18 lesions. The most distinct feature was the well-defined granular staining pattern of the superficial layer in 8 out of 10 HPV 6/11 lesions, as contrasted to the homogeneous pattern in 24 out of 28 HPV-16-infected lesions. In superficial cells, regressed lesions exhibited intense staining in 9/13 (69.2%), as compared with only 4/10 (40%) of the progressed lesions.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Cervix Uteri; Epithelium; Female; Genital Diseases, Female; Humans; Immunohistochemistry; Keratins; Papillomaviridae; Peptides; Staining and Labeling; Tumor Virus Infections; Uterine Cervical Neoplasms | 1990 |
Analysis of human papillomavirus type 16 E6-E7 transcription in cervical carcinomas and normal cervical epithelium using the polymerase chain reaction.
Cervical biopsies were collected from Birmingham women having cervical intraepithelial neoplasia or invasive cervical carcinoma and normal controls, and examined for the presence of human papillomavirus type 16 (HPV-16) E6-E7 DNA and mRNA using an adaptation of the polymerase chain reaction. HPV-16 E6-E7 sequences were detected in all abnormal biopsies and in 90% of the normal biopsies examined, confirming previous studies describing the high prevalence of cervical HPV-16 infection. While we were unable to identify any qualitative differences in RNA transcripts from the p97 promoter, substantial quantitative differences in HPV-16-specific early region transcripts between normal and cytologically abnormal cervices were observed. These results suggest that although the level of E6-E7 transcription may contribute to the malignant phenotype, additional factors are likely to be important in the development of cervical neoplasia. Topics: Cervix Uteri; DNA, Viral; Epithelium; Female; Humans; Keratins; Oligonucleotide Probes; Papillomaviridae; Polymerase Chain Reaction; RNA, Viral; Transcription, Genetic; Uterine Cervical Neoplasms | 1990 |
Keratin subtypes in carcinomas of the uterine cervix: implications for histogenesis and differential diagnosis.
Normal epithelia and carcinomas of the human uterine cervix were studied by monoclonal antibodies chain specific for cytokeratins 4, 8, 10, 13, 14, 18, and 19. Most cells in 13 examined squamous carcinomas revealed a cytokeratin phenotype detected in ectocervical basal cells and endocervical subcolumnar reserve cells: 8+, 14+, 18+, 19+, 4-, 10-, 13-. We propose that these two cell types are closely related or identical and that squamous carcinoma of the cervix originates in this cell type. In more differentiated tumor cells cytokeratins 4, 10, and 13, which are present in suprabasal layers of the normal ectocervical epithelium, were coexpressed with basal cell cytokeratins. Thus, contrary to previous beliefs, all cytokeratins detected in carcinomas were also present in normal epithelium of uterine cervix. The cytokeratin profile of cervical adenocarcinomas corresponded to that of columnar endocervical cells (8+, 18+, 19+), although two of the three adenocarcinomas also expressed cytokeratin 4, which in the normal endocervix was detected in scattered single columnar cells only. The new monoclonal antibody DE-K14, specific for cytokeratin 14, proved a specific marker of subcolumnar reserve cells in the endocervix. It was also the only one that reacted with all cervical squamous carcinomas but with none of the cervical adenocarcinomas and, as such, has a potential value for pathological differential diagnosis of cervical tumors. Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cervix Uteri; Electrophoresis, Gel, Two-Dimensional; Epithelial Cells; Epithelium; Female; Fluorescent Antibody Technique; Humans; Immunoblotting; Keratins; Reference Values; Uterine Cervical Neoplasms | 1990 |
Patterns of mRNA for epidermal growth factor receptor and keratin B-2 in normal cervical epithelium and in cervical intraepithelial neoplasia.
Patterns of epidermal growth factor receptor (EGFR) and keratin B-2 (KB2) mRNA localization were studied in samples of normal cervical squamous epithelium and in samples of cervical intraepithelial neoplasia (CIN). 35S-Labeled EGFR and KB2 DNA probes were used for in situ hybridization on formalin-fixed tissue sections. Normal cervical squamous epithelium showed predominantly basal and parabasal expression of EGFR mRNA and suprabasal and midepithelial localization of KB2 mRNA. CIN lesions with moderate to severe dysplasia were generally characterized by continued expression of EGFR mRNA and decreased KB2 mRNA in midepithelial locations. Ratios of KB2 mRNA levels at the basal layer to KB2 mRNA levels at the midepithelial location were increased in moderate and severe dysplasia (CIN II and III) compared with normal epithelium (P less than .01). Ratios of EGFR mRNA levels at the midepithelial level to those of EGFR mRNA at the basal layer were increased in moderate to severe dysplasia compared with normal epithelium. These findings indicate a possible in vivo role of EGFR gene expression in normal and neoplastic proliferation and in prevention of differentiation of the cervical epithelium. Topics: Cell Differentiation; Cervix Uteri; Epithelial Cells; ErbB Receptors; Female; Gene Expression; Humans; Keratins; Nucleic Acid Hybridization; RNA, Messenger; Transcription, Genetic; Uterine Cervical Neoplasms | 1990 |
Mucoepidermoid carcinoma of uterine cervix stage IB. Long-term follow-up, histochemical and immunohistochemical study.
Twelve women with mucoepidermoid carcinoma of the cervix uteri were followed for 2-15 years after diagnosis. Three patients died within 14 months. All had lymph node metastases and/or vascular involvement and exhibited tumor invasion to a depth of 1.2-3.2 cm. Mucoepidermoid carcinoma is defined as a tumor with the appearance of squamous cell carcinoma without any glandular pattern and with demonstrable intracellular mucin. The mucin is best demonstrated by alcian blue and periodic acid-Schiff-diastase. In 265 cases of squamous cell carcinoma, stage IB, lymph node metastases were present in 14%. In the cases of mucoepidermoid carcinoma, the prevalence of nodal metastases was 33%. Because mucoepidermoid carcinomas appear to be more aggressive lesions than squamous cell carcinomas are, it may be advisable to stain all cervical squamous carcinomas for mucin if they demonstrate finely vacuolated cytoplasm and lack peripheral palisading. Immunohistochemical studies for carcinoembryonic antigen (CEA), keratin, and epithelial membrane antigen were positive in all tumors to varying degrees. The detection of CEA may be of additional help in establishing a diagnosis. Topics: Adult; Aged; Antibodies, Monoclonal; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Mucins; Staining and Labeling; Uterine Cervical Neoplasms | 1990 |
Detection of metastatic vulvar and cervical squamous carcinoma in regional lymph nodes by use of a polyclonal keratin antibody.
A polyclonal keratin antibody (pK), a marker for epithelial cells, was used to evaluate lymph nodes (LNs) from patients with invasive squamous carcinomas of the cervix (CxCa) or vulva (VCa) to determine whether this technique could increase the detection of metastases (mets) over that obtained by light microscopy using a routine hematoxylin and eosin (H&E)-stained slide. The LN status of 15 cases of stage 1B CxCa and 14 cases of VCa was determined using a routine H&E slide. Subsequently, all LNs were resectioned and examined using a pK immunoperoxidase stain. In 329 lymph nodes from 14 cases of CxCa and 9 cases of VCa originally classified as LN-negative, only a single met was detected by the pK technique. In five cases of VCa and one case of CxCa (121 LNs), with LN mets or LN tumor emboli on the original H&E, three additional microscopic foci of mets were detected by pK. Of the four foci of mets discovered by pK, one was visible in retrospect on the original H&E section, and all four were easily identified on examination of a serial H&E section adjacent to the pK section. These results suggest that pK stains are unlikely to significantly increase our sensitivity in detecting mets in CxCa and VCa, beyond merely further sectioning and H&E staining of nodes. Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Eosine Yellowish-(YS); Female; Hematoxylin; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Staining and Labeling; Uterine Cervical Neoplasms; Vaginal Smears; Vulvar Neoplasms | 1990 |
Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma.
Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma. Topics: Carcinoma; Cell Transformation, Viral; Cells, Cultured; DNA, Viral; Electrophoresis, Agar Gel; Epidermal Cells; Epidermis; Female; Humans; Keratins; Papillomaviridae; Plasmids; RNA, Messenger; RNA, Viral; Transfection; Uterine Cervical Neoplasms | 1989 |
Combined immuno- and non-radioactive hybridocytochemistry on cells and tissue sections: influence of fixation, enzyme pre-treatment, and choice of chromogen on detection of antigen and DNA sequences.
Conditions for combination of DNA in situ hybridization, using biotinylated DNA probes, with immunohistochemistry were investigated on cryostat sections, cytological preparations, and paraffin sections. We found that cryostat sections and cytological preparations are suitable for in situ hybridization of target DNA after fixation in acetone, methanol, ethanol, or Carnoy without further proteinase pretreatment. Acetone is also very suitable for immunostaining of cell surface or cytoskeleton antigens. We therefore performed combined immunoenzyme and in situ hybridization staining using this fixative. The best results were obtained when immunoperoxidase staining with diaminobenzidine/H2O2 was followed directly by in situ hybridization. In addition to immunoperoxidase, alkaline phosphatase-antialkaline phosphatase (APAAP) staining with naphthol ASBI phosphate and New Fuchsin as a substrate could be used. In most instances, detection of the biotinylated hybrid with a streptavidin-biotinylated polyalkaline phosphatase method using nitroblue tetrazolium and 5-bromo-4-chloro-3-indolylphosphate as the substrate was preferable. The double stainings were studied on the following test models: (a) frozen tonsil sections: cell surface antigens (pan T) and ribosomal DNA; (b) frozen genital condyloma sections; cytokeratins and human papillomavirus type 6 + 11 (HPV-6/11) DNA; (c) CaSKi cells: cytokeratins and HPV-16 DNA; (d) infected fetal lung fibroblasts: vimentin and cytomegalovirus (CMV) DNA. An adapted procedure was followed on routinely formaldehye-fixed and paraffin-embedded condyloma tissue. Immunoperoxidase staining for papilloma virus capsid antigen could be combined with DNA in situ hybridization with HPV-6/11 DNA. In this model, however, the accessibility of the target DNA had to be improved by enzyme treatment after the immunostaining and before starting the in situ hybridization. Topics: Antigens, Surface; Base Sequence; Chromogenic Compounds; Condylomata Acuminata; Cytomegalovirus; DNA Probes; DNA Probes, HPV; DNA, Ribosomal; Endopeptidases; Female; Fibroblasts; Fixatives; Humans; Immunohistochemistry; Keratins; Male; Nucleic Acid Hybridization; Palatine Tonsil; Uterine Cervical Neoplasms; Vimentin | 1989 |
Cytokeratin expression in cervical epithelium: an immunohistological study of normal, wart virus-infected and neoplastic tissue.
In this study using a panel of anticytokeratin antibodies and an indirect immunoperoxidase method, we examined cervical squamous epithelia including mature stratified epithelium, immature squamous metaplasia, CIN 1, 2 and 3, wart virus infection and squamous carcinoma. Changes from the normal patterns of staining were inconsistently seen in CIN 1 and 2, but in CIN 3 the changes were more marked, and consisted of a loss of stratification of the staining pattern and a patchy reduction in staining. Invasive carcinomas showed a similar staining pattern to CIN 3 lesions. Topics: Carcinoma, Squamous Cell; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Papillomaviridae; Tumor Virus Infections; Uterine Cervical Diseases; Uterine Cervical Neoplasms | 1989 |
Heterogeneous expression of keratin, involucrin, and extracellular matrix among subpopulations of a poorly differentiated human cervical carcinoma: possible relationships to patterns of invasion.
Undifferentiated cervical carcinomas vary considerably in their intercellular organization and patterns of invasion. In spite of its clinical significance, the basis for such variation is poorly understood. We investigated the cellular properties that may be responsible for this diversity, using as a model two human cervical carcinoma cell lines that were derived from the same tumor specimen and the same clone. It was shown previously that, in spite of their common origin, each line forms a histologically distinct type of undifferentiated carcinoma when heterotransplanted in vivo: cells of line C-4I grow as compact expanding masses with central necrosis, while tumors of line C-4II infiltrate host tissues as small, well-vascularized, dispersed cell groups. The characteristic behavior of each line was retained in culture, where C-4I cells formed highly multilayered cohesive colonies, while C-4II cells formed diffuse, monolayered colonies and shed into the culture medium. These observations as well as ultrastructural data suggested that each line may be arrested at a different stage of stratified squamous differentiation. In the present study, this hypothesis was tested by examining specific differentiation markers. An analysis of the cultures by immunofluorescence microscopy and immunoblotting revealed that keratin was more abundant in the compact C-4I line than in the dispersed C-4II line. C-4I cells expressed keratins 5, 6, 8, 16, 18, and 19, while C-4II expressed only keratins 8, 16, 18, and 19. In the multilayered C-4I colonies, involucrin-positive cells occurred in the apical cell layers only. In C-4II, involucrin-positive cells occurred in monolayers and domes, and they were most consistently located apically in crowded cultures. Laminin was secreted by both lines, but only C-4II cells deposited a fibronectin matrix. The results suggest that C-4I cells resemble normal cervical cells at the spinous stage of stratified squamous differentiation, while C-4II cells resemble basal/suprabasal cells. The different growth patterns of the tumors, formed by the lines in vivo, therefore likely reflect functional and behavioral differences that normally exist between spinous and basal cervical epithelial cells. The results suggest that differentiation-related functional properties may lead to histological diversity among cervical carcinomas that are categorized as undifferentiated by histopathological criteria. Topics: Carcinoma; Cell Differentiation; Female; Fibronectins; Humans; Keratins; Laminin; Neoplasm Proteins; Protein Precursors; Tumor Cells, Cultured; Uterine Cervical Neoplasms | 1989 |
[Retrospective immunohistologic search for metastases using monoclonal anti-cytokeratin antibodies in lymph nodes of patients with stage Ib-IIb cervix cancer dying within 5 years].
With immunohistological methods using monoclonal antibodies more metastases were detected in carcinomas today. We examined 10 women, where the carcinoma of the cervix was removed today in healthy and where the lymph nodes were free of metastases. With use of the monoclonal cytokeratin-antibody lu-5 it was not possible to improve the diagnostic. In a histomorphological differentiation of grade 2 or 3 a radiation should be considered. Topics: Adult; Antibodies, Monoclonal; Desmin; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplastic Cells, Circulating; Retrospective Studies; Uterine Cervical Neoplasms; Vimentin | 1989 |
An immunohistochemical study of small-cell and poorly differentiated carcinomas of the cervix using neuroendocrine markers.
Small-cell and poorly differentiated carcinomas of the cervix were studied immunohistochemically for several neuroendocrine and epithelial markers. Neuroendocrine markers were frequently expressed in small-cell carcinomas with argyrophilia; of the seven such tumors, four were immunoreactive with anti-chromogranin, seven with antineuroendocrine, five with anti-Leu 7, and seven with anti-neuron-specific enolase. Only neuron-specific enolase, however, was expressed in two of the three small-cell carcinomas without argyrophilia. On the other hand, one of the epithelial markers, epithelial membrane antigen, was strongly positive in all three small-cell carcinomas without argyrophilia and all seven poorly differentiated carcinomas, while it was expressed only weakly and focally in all small-cell carcinomas with argyrophilia except in one case. In conclusion, it is suggested that the immunohistochemical demonstration of several neuroendocrine markers may be helpful in diagnosing neuroendocrine carcinoma of the cervix as a supplement to conventional light microscopy, silver staining, and electron microscopy. Topics: Adenocarcinoma; Antigens, Neoplasm; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chromogranins; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Phosphopyruvate Hydratase; Uterine Cervical Neoplasms | 1989 |
Analysis of a 24-kilodalton (KD) protein in the human uterine cervix during abnormal growth.
The authors have previously studied the presence and distribution of a 24-kilodalton (KD) estrogen-regulated protein in the human normal cervix (Am J Obstet Gynecol 1986; 155:1090-1096). This protein has recently been identified as a heat-shock protein, and in order to continue its study the authors have now examined its expression in preneoplastic to neoplastic cervical samples. The study involved 53 patients, the presence of 24-KD protein together with keratin and carcinoembryonic antigen (CEA) was investigated by immunohistochemical analysis. Cytosol samples from 15 patients with squamous cervical carcinomas were also studied by the Western blot technique, and the presence of estrogen receptors was analyzed biochemically. The 24-KD protein was observed in cervical intraepithelial neoplasias (CIN), but it was not useful to identify the different degrees of CIN examined. The 24-KD protein, keratin, and CEA were predominantly expressed in well and moderately differentiated squamous carcinomas in the more differentiated areas, and the protein was also found in cervical adenocarcinomas. The presence of 24-KD protein did not correlate with that of estrogen receptors in squamous cervical carcinomas. The Western blot and the immunohistochemical studies revealed that the antibody to 24-KD protein does not cross-react with epitopes of CEA and keratins. Topics: Adenocarcinoma; Blotting, Western; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cervix Uteri; Female; Heat-Shock Proteins; Humans; Immunohistochemistry; Keratins; Molecular Weight; Precancerous Conditions; Receptors, Estrogen; Uterine Cervical Neoplasms | 1989 |
[Clinicopathologic and immunohistochemical study on 8 cases of malignant mixed müllerian tumor].
The clinico-pathological features of eight cases of malignant mixed müllerian tumor, a rare neoplasm composed of an admixture of epithelial and stromal elements, are reported. Four of the tumors located in the endometrium, three in the cervix and one in the ovary. Microscopically, the epithelial elements ranged from poorly to well differentiated adenocarcinoma. Homologous stromal sarcoma cells were present in six tumors and heterologous elements were also seen in the other two tumors. Immunohistochemical studies showed diffuse cytoplasmic staining of keratin in the epithelial elements of all the eight cases. Sarcomatous cells were positive focally for keratin in four spindle cell sarcoma cases. Desmin immunoreaction was moderately positive in the sarcomatous element of four neoplasms. Follow-up result was available in 7 patients of whom 3 survived and 4 died from recurrence or metastasis. Immunohistochemical findings support the stem cell origin of this tumor. Topics: Adult; Desmin; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Neoplasms, Germ Cell and Embryonal; Uterine Cervical Neoplasms | 1989 |
"Adenoid cystic" carcinoma and adenoid basal carcinoma of the uterine cervix. A study of 28 cases.
Adenoid cystic carcinoma (ACC) and adenoid basal carcinoma (ABC) of the uterine cervix are rare tumors that have often been regarded as a single entity. We studied 28 cases of these neoplasms, with 14 cases in each category. Most patients were over 60 years of age, and there was a high proportion of black women. The majority of the women with ACC presented with postmenopausal bleeding and had an obvious mass on pelvic examination. Despite the tumors' architectural similarity to ACC of the salivary gland, microscopic examination of the cervical carcinomas showed necrosis, a high mitotic rate, and greater nuclear pleomorphism. In all but one of the cases, the tumor cells were negative for S-100 protein on immunoperoxidase staining--a finding that provides evidence against a myoepithelial component. However, S-100-positive dendritic cells were present in the stroma of the tumors and among the neoplastic cells. The patients with ABC were usually asymptomatic, without a gross abnormality of the cervix. Microscopic examination disclosed small nests of basaloid cells, almost always beneath, and often arising from, in situ or small invasive squamous cell carcinomas. In contrast to ABC, ACC was often complicated by local recurrence or distant metastasis. We conclude that ACC of the uterine cervix differs from ACC of salivary gland origin and is also distinct clinically and pathologically from cervical ABC. Topics: Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma in Situ; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Female; Humans; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Neoplasms, Multiple Primary; S100 Proteins; Uterine Cervical Neoplasms | 1988 |
Expression of cytokeratin polypeptides in human papillomavirus (HPV) lesions of the uterine cervix: 1. Relationship to grade of CIN and HPV type.
A series of 74 punch biopsies, derived from 513 women prospectively followed for cervical human papillomavirus (HPV) infections (including HPV-NCIN, HPV-CIN I, HPV-CIN II, and HPV-CIN III lesions), and 43 control cases (consisting of normal epithelia, nonspecific cervicitis, and classical CIN lesions) were analysed for expression of cytokeratin polypeptides using the ABC technique and monoclonal antibodies SK 56-23 (wide-spectrum antibody), SK 60-61 (specific for keratins 8 and 18), and SK 2-27 (detecting keratins 14, 16, and 17). HPV typing was carried out using the in situ hybridization technique with DNA probes for HPV 6, 11, 16, 18, and 31. All layers of the exocervical epithelium were regularly stained with the antibody SK 56-23, and the staining pattern remained unaltered in all cervical lesions studied. In contrast to the normal exocervical epithelium, which remained negative with SK 60-61, positive staining was observed in 3 of 15 cervicitis cases and 6 of 23 classical CIN lesions. Interestingly, the majority (69 of 74, 93.2%) of both HPV-NCIN and HPV-CIN lesions showed positive staining with this antibody either in all layers or in suprabasal cells. Antibody SK 2-27 stained the basal cells of the normal exocervical epithelium with remarkable specificity. In 18 of 19 HPV-NCIN lesions, basal cells could not be stained by SK 2-27 monoclonal, but the suprabasal cells were stained instead. In HPV-CIN, but not in classical CIN, this antibody demonstrated the presence of the epitope typical of the cytokeratins 14, 16, and 17 in all layers of the epithelium, the highest frequency (9 of 12, 75%) being found in HPV 16-induced lesions. These disturbances of cytokeratin patterns in cervical epithelium could be associated with cell transformation by HPV, leading to development of HPV-CIN, and could be specific for this virus. The present data are of interest in assessing the stage of maturation of the squamous cells in progressing cervical HPV infections. Topics: Antibodies, Monoclonal; Cervix Uteri; Female; Humans; Immunohistochemistry; Keratins; Papillomaviridae; Peptides; Prospective Studies; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1988 |
Expression of the cytokeratin marker CAM 5.2 in cervical neoplasia.
It has been suggested that cytokeratin CAM 5.2 is a useful marker to indicate malignant transformation and invasive potential in cervical neoplasia. In this study we examined normal ectocervical epithelium, endocervical squamous metaplasia, cervical intra-epithelial neoplasia (CIN) and invasive carcinoma by the indirect immunoperoxidase method using commercially available CAM 5.2. Positive staining was seen in 12 of 42 (28%) invasive carcinomas and in 2 of 26 specimens of CIN III. No positive staining was observed in any case of CIN II (22 specimens), CIN I (19), squamous metaplasia (21) or normal ectocervical epithelium (16). These results suggest that although CAM 5.2 expression is found in only 28% of cervical squamous carcinoma, it is highly specific for malignant transformation of cervical squamous epithelium. In view of its potential diagnostic value in doubtful cases of CIN III and squamous cell carcinoma, the specificity and sensitivity of CAM 5.2 expression in cervical neoplasia need to be examined in other laboratories under various processing schedules. Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Cervix Uteri; Female; Humans; Immunoenzyme Techniques; Keratins; Uterine Cervical Neoplasms | 1988 |
Cytokeratins in cervical dysplasia and neoplasia: a comparative study of immunohistochemical staining using monoclonal antibodies NCL-5D3, CAM 5.2, and PKK1.
The expression of low molecular weight cytokeratins (normally expressed only in simple epithelia) in intraepithelial neoplasia of grade CIN III or greater in cervical biopsies has recently been described by Bobrow et al. Our study of 127 cases confirms this finding and in addition we compare the use of three monoclonal antibodies, namely NCL-5D3, CAM 5.2, and PKK1, in demonstrating the phenomenon. Both NCL-5D3 and CAM 5.2 give consistently negative results for non-neoplastic stratified squamous epithelium, as well as CIN I and CIN II lesions, whilst staining about 30 per cent of CIN III biopsies and most carcinomas. PKK1, on the other hand, stained 50 per cent of non-neoplastic epithelia and thus did not serve as a marker of severe dysplasia. The possible implications of these observations are discussed. Topics: Antibodies, Monoclonal; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Humans; Keratins; Staining and Labeling; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1988 |
Characterization of normal human exocervical epithelial cells immortalized in vitro by papillomavirus types 16 and 18 DNA.
An in vitro system for studying the interaction between human papillomavirus (HPV) 16 and 18 recombinant DNA and normal human exocervical epithelial cells is described. Eight HPV-immortalized human exocervical epithelial cell lines were established; all the lines contained either integrated HPV16 or 18 sequences and expressed HPV mRNAs. Thus, integration and expression appear to be required for immortalization. Immortalized cells (greater than 200 population doublings to date) divided rapidly (doubling time of 30 to 46 h) and morphologically resembled primary cultures of normal human exocervical epithelial cells. They expressed a keratin pattern consistent with their origin from exocervical epithelium. When cultured at high density or in the presence of serum they terminally differentiated. Sublines resistant to terminal differentiation were selected by growth in serum-supplemented medium. Keratin pattern changes suggest they have some properties in common with cervical squamous carcinoma cells. However, HPV-immortalized cell lines were not tumorgenic in nude mice. Thus, HPV16/18 is not carcinogenic by itself. These cell lines represent an appropriate model for studying factors that regulate HPV gene expression in normal cervical epithelial cells and examining the influence of cocarcinogens on neoplastic progression. Topics: Animals; Cell Line; Cell Transformation, Viral; Cervix Uteri; DNA, Viral; Epithelium; Female; Humans; Keratins; Mice; Papillomaviridae; RNA, Messenger; Transfection; Uterine Cervical Neoplasms | 1988 |
Human papillomavirus type 16 alters human epithelial cell differentiation in vitro.
Human papillomavirus (HPV) types 16, 18, 31, and 33 have been implicated as etiologic agents of cervical and penile cancer. Using a cell culture system for keratinocytes which allows stratification and production of differentiation-specific keratins, we have examined the effects of one of these viruses, HPV-16, on the differentiation capabilities of human epithelial cells. A plasmid containing the HPV-16 genome and a neomycin-selectable marker was transfected into primary human epidermal cells and SCC-13 cells, an immortalized squamous cell carcinoma cell line. Cloned neomycin-resistant cell lines were isolated and examined by cell culture on raised collagen rafts. Cell lines containing HPV-16 DNA retained the ability to stratify and express differentiation-specific keratins in the raft system but otherwise failed to differentiate normally. The histological abnormalities induced by HPV-16 closely resembled those seen in genital intraepithelial neoplasia in vivo. Hence, our results support the role of HPV-16 as an etiologic agent in the development of genital neoplasias and suggest a specific system for the study of HPV-16-induced epithelial cancers. Topics: Blotting, Southern; Cell Differentiation; Cell Line; Epidermal Cells; Female; Humans; Keratins; Male; Papillomaviridae; Penile Neoplasms; Precancerous Conditions; Transfection; Uterine Cervical Neoplasms | 1988 |
Quantitative keratinocyte assay detects two biological activities of human papillomavirus DNA and identifies viral types associated with cervical carcinoma.
Keratinocytes electroporated with human papillomavirus (HPV) DNA (HPV-6, 11, 16 and 18) exhibited an increased cellular proliferation which was quantitated as microcolony and macrocolony formation. However, only macrocolonies induced by HPV-16 or HPV-18 DNA (the two viral types most commonly found in human cervical carcinomas) gave rise to proliferating, poorly-stratified colonies when grown in the presence of serum and calcium. Hydrocortisone increased the frequency of these differentiation-resistant colonies, and studies showed that they were immortalized, contained one copy of viral DNA per cell, expressed three discrete species of viral RNA and synthesized the viral E7 protein. HPV-induced cellular proliferation and altered differentiation are therefore separable events and may represent the activity of different viral genes. Topics: Biological Assay; Blotting, Southern; Calcium; Cell Differentiation; Cell Division; Cell Transformation, Viral; DNA, Viral; Epidermal Cells; Female; Humans; In Vitro Techniques; Keratins; Male; Papillomaviridae; Uterine Cervical Neoplasms; Viral Proteins | 1988 |
Cervical adenocarcinoma arising in florid mesonephric hyperplasia: report of a case with immunocytochemical studies.
A case of mesonephric adenocarcinoma of the uterine cervix arising in florid mesonephric hyperplasia is reported. The reviewed literature contained many cases of cervical "mesonephroma" but only a few of these were considered to be demonstrably of mesonephric origin. These tumors were usually associated with proliferating mesonephric remnants in the cervix. Similar tubuloglandular mesonephric proliferations without formation of a frankly malignant tumor have also been described in the cervix, most recently as florid mesonephric hyperplasia. This latter entity appears to be benign. Carcinoembryonic antigen (CEA) was focally positive in this cervical adenocarcinoma, suggesting that CEA may not be useful in distinguishing this variant from the more common mullerian adenocarcinoma of the cervix. Topics: Carcinoembryonic Antigen; Female; Humans; Immunoenzyme Techniques; Keratins; Mesonephroma; Middle Aged; Uterine Cervical Neoplasms | 1987 |
Diversity of cytokeratins in carcinomas.
Topics: Adenocarcinoma; Breast Neoplasms; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cytoskeleton; Diagnosis, Differential; Epithelium; Female; Gastrointestinal Neoplasms; Humans; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Lung Neoplasms; Neoplasms; Skin Neoplasms; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms | 1987 |
Characterization of four new cell lines derived from human squamous carcinomas of the uterine cervix.
Four continuous cell lines were established from 15 biopsies of human squamous carcinomas of the uterine cervix, two from women less than 35 years old. All four lines grew as adherent monolayers and had epitheloid morphology. All required initial 3T3 feeder layer support and hydrocortisone and insulin for growth and have now been grown in vitro for at least 12 months. The individual lines possessed unique isozyme patterns and were distinct from the HeLa cell line. All were tumorigenic in nude mice. In vitro colony forming efficiencies ranged from 2 to 30% in a monolayer anchorage dependent assay but were only from 0.0025 to 0.6% when assayed in soft agar. The lines were all aneuploid with mean chromosome numbers ranging from 71 to 75. Analysis of intermediate filament expression showed that all lines were positive for cytokeratin expression and two were positive for vimentin expression. These low-passage cell lines represent a panel of new in vitro models of carcinoma of the cervix. They should be useful for the investigation of chemosensitivity, of the involvement of human Papillomavirus in this disease, and as models of squamous cell differentiation. Topics: Adult; Carcinoma, Squamous Cell; Cell Line; Female; Humans; Intermediate Filaments; Isoenzymes; Karyotyping; Keratins; Middle Aged; Neoplasm Transplantation; Transplantation, Heterologous; Uterine Cervical Neoplasms; Vimentin | 1987 |
Transcriptional regulation of the human papillomavirus-16 E6-E7 promoter by a keratinocyte-dependent enhancer, and by viral E2 trans-activator and repressor gene products: implications for cervical carcinogenesis.
The transcriptional promoter of the candidate E6-E7 transforming gene region of human papillomavirus (HPV)-16 (P97) was active in transiently transfected cervical carcinoma cells when linked to the HSV-1 tk or bacterial cat genes. Sequences 5' to P97 contain a short enhancer element responding to cellular factor(s) in uninfected human foreskin keratinocytes and in cervical carcinoma cells, but not in human or animal fibroblasts. The E2 trans-activator products of HPV-16 or of the related bovine papillomavirus (BPV)-1 further elevated HPV-16-driven transcripts in co-transfections, and required the presence of E2-binding ACC(N)6GGT cores in cis. A 'short E2' C-terminal repressor gene product (sE2) of HPV-16 or the BPV-1 sE2 repressor not only inhibited viral E2 trans-activation, but also suppressed enhancer response to keratinocytic factors. Suppression by the sE2 products was abolished by deletion of the E2-binding cores in cis or by a mutation in the sE2 DNA binding domain. The keratinocyte-dependent enhancer is likely to contribute to the epithelial cell tropism of HPV-16, and may direct persistent E6-E7 gene transcription in response to cellular factors in cervical carcinoma cells in which the viral E2 genes are inactive. Topics: Animals; Cell Line; Cell Transformation, Neoplastic; Enhancer Elements, Genetic; Epidermal Cells; Female; Gene Expression Regulation; Genes; Genes, Viral; Humans; Keratins; Papillomaviridae; Promoter Regions, Genetic; Transcription, Genetic; Transfection; Uterine Cervical Neoplasms | 1987 |
An immunohistochemical study of difference between cervical and endometrial adenocarcinomas of the uterus--using monoclonal antibodies of CEA and cytokeratin.
Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Carcinoembryonic Antigen; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Uterine Cervical Neoplasms; Uterine Neoplasms | 1987 |
An immunohistochemical study of difference between cervical and endometrial adenocarcinomas of the uterus--using monoclonal antibodies of vimentin and cytokeratin.
Topics: Adenocarcinoma; Antibodies, Monoclonal; Diagnosis, Differential; Female; Humans; Keratins; Uterine Cervical Neoplasms; Uterine Neoplasms; Vimentin | 1987 |
Expression of low molecular weight cytokeratin proteins in cervical neoplasia.
CAM 5.2 is a monoclonal antibody which identifies lower molecular weight cytokeratin proteins (50, 43 and 38 kD). It is an antibody which works reliably on formalin-fixed, paraffin-embedded tissues. In this study, using CAM 5.2 in the indirect immunoperoxidase method we have examined ectocervical epithelium ranging from normal, through metaplasia and cervical intraepithelial neoplasia to invasive squamous carcinoma. CAM 5.2 is demonstrated to be a useful indicator of changes associated with malignant transformation in the ectocervix. Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cervix Uteri; Female; Humans; Immunoenzyme Techniques; Keratins; Metaplasia; Molecular Weight; Uterine Cervical Neoplasms | 1986 |
Tissue polypeptide antigen and keratins in cervical neoplasia.
Antibodies against tissue polypeptide antigen (TPA) and keratins of high molecular weight (62-67 kD) were used to indicate different stages of cell differentiation. The immunohistochemical study was carried out by indirect immunofluorescence. In dysplasia, particularly in CIN grades II to III, TPA labeling comprised not only basal layer cells (as seen in normal mucosa) but more superficial layers as well. Expression of keratins of high molecular weight was reduced to small foci of keratinization and scattered dyskeratotic cells. In typical small cell anaplastic carcinoma in situ, TPA antibodies were observed to label all epithelial cell layers. There was no reactivity with antibodies against keratins of high molecular weight. In invasive cancer, TPA staining was closely related to the degree of maturation. Nonkeratinized tumor zones were entirely labeled by TPA antibodies, whereas keratinized tumor foci were negative for TPA except for peripheral tumor cell layers. In invasive cancer, keratins of high molecular weight were restricted to differentiated portions of the tumor. Our immunohistochemical findings support the present concepts of TPA (as a member of the heterogeneous keratin family) as an indicator of cell differentiation. Immunohistochemical demonstration of keratins of different molecular weight offers a method of assessing squamous differentiation at the cervical transformation zone and in cervical cancer and precancer. Topics: Antigens, Neoplasm; Biopsy; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Fluorescent Antibody Technique; Humans; Keratins; Neoplasm Staging; Peptides; Tissue Polypeptide Antigen; Uterine Cervical Neoplasms | 1986 |
Intermediate filaments in endometrial and endocervical carcinomas. The diagnostic utility of vimentin patterns.
We examined the distribution of high- and low-molecular-weight cytokeratins, vimentin, and carcinoembryonic antigen (CEA) in normal endometrial glands and endocervical glands (20 cases each) and in endometrial and endocervical adenocarcinomas (29 cases and 15 cases respectively). Low- and high-molecular-weight cytokeratin staining was present in normal endometrial and endocervical epithelium and in carcinomas. Coexpression of vimentin and cytokeratin was universally present in normal proliferative endometrial glands, with marked decrease or absence of vimentin staining in secretory phase patterns. Vimentin staining had a perinuclear distribution within the cells, in contrast to the cytokeratins, which stained diffusely. Vimentin was found in only 65% of endometrial adenocarcinomas. Staining was typically focal as well as regional in portions of the tumors. Vimentin was never observed in normal or neoplastic endocervical epithelium. Ultrastructural studies corroborate the perinuclear vimentin immunostaining pattern we observed in endometrial adenocarcinomas. CEA staining results were similar to those previously reported. These data indicate that the presence of vimentin may readily distinguish endometrial from endocervical carcinoma and is diagnostically useful in the study of metastatic adenocarcinomas. Topics: Adenocarcinoma; Carcinoembryonic Antigen; Cytoskeleton; Diagnosis, Differential; Female; Humans; Intermediate Filaments; Keratins; Microscopy, Electron; Retrospective Studies; Uterine Cervical Neoplasms; Uterine Neoplasms; Vimentin | 1986 |
Cytokeratin expression in squamous metaplasia of the human uterine cervix.
The expression of cytokeratin polypeptides in squamous metaplasia of the human uterine cervix was investigated by immunocytochemical labeling with polypeptide-specific antibodies against cytokeratins. Immunofluorescence microscopic examination of cervical tissues using various monoclonal antibodies indicated that squamous cervical metaplasia expresses a unique set of cytokeratin polypeptides, this being distinctively different from that expressed by all of the normal epithelial elements of the exo- and endocervix. The development of metaplastic foci was accompanied by the expression of cytokeratin polypeptide no. 13, which is commonly detected in stratified epithelia, and by a reduction in the level of polypeptide no. 18, which is typical of simple epithelia. The 40-kilodalton cytokeratin (no. 19) described by Moll et al., which is abundant in the columnar and reserve cells of the endocervix, was found throughout the metaplastic lesions. Only in 'well-differentiated' metaplasias did we detect polarity of cytokeratin expression reminiscent of the staining patterns in the exocervix. This was manifested by the exclusive labeling of the basal cell layer(s) with antibodies KB 8.37 and KM 4.62, which stain the basal cells of the exocervix. Furthermore, a comparison of cervical metaplasia with squamous areas occurring within endometrial adenocarcinomas pointed to a close similarity in the cytokeratin expression of the two. We discuss the use of cytokeratins as specific markers of squamous differentiation, the relationships between squamous metaplasia and cervical neoplasia, and the involvement of reserve cells in the metaplastic process. Topics: Adult; Aged; Antibodies, Monoclonal; Cervix Uteri; Collodion; Electrophoresis, Polyacrylamide Gel; Epithelium; Female; Fluorescent Antibody Technique; Humans; Keratins; Metaplasia; Microscopy, Fluorescence; Middle Aged; Peptides; Uterine Cervical Neoplasms | 1986 |
Low molecular weight cytokeratin proteins in cervical neoplasia.
Topics: Adult; Female; Humans; Keratins; Middle Aged; Molecular Weight; Neoplasm Proteins; Uterine Cervical Neoplasms | 1986 |
Monoclonal antibodies raised to colorectal carcinoma antigens.
The search for tumour markers was intensified with the advent of monoclonal antibody technology. To date no tumour specific markers have been found. Despite this, monoclonal antibodies have helped to identify cells in terms of their origin and function and therefore added a different dimension to studies of both benign and malignant disease processes. Advances in molecular biology have made cooperation between scientists and clinicians in all branches of medicine essential in order to piece together a more complete picture of any disease. This article describes the production and characterisation of two epithelial specific monoclonal antibodies (CAM5.2 and CAM17.1) with potential clinical value by a surgeon temporarily transposed to a laboratory environment. Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Surface; Colonic Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Rectal Neoplasms; Uterine Cervical Neoplasms | 1986 |
Common antigenic sites on exfoliated cells derived from cervical carcinoma and in tumor cells of nonuterine origin as demonstrated by monoclonal antibodies in immunoperoxidase assay.
The binding characteristics of monoclonal antibodies produced against a variety of human tumor cells were studied on cervical carcinoma cell lines and on exfoliated cells of cervical smears. The latter included normal epithelial cells, cells derived from cervical intraepithelial neoplasia, and cells from squamous cell carcinoma. Monoclonal antibodies that bound in immunoperoxidase assays to ethanol-fixed smears of cultured human tumor cells but not to normal cervical smears were screened on cervical smears containing malignant cells. Of the six antibodies selected for detailed studies, two each had been produced against bladder carcinoma and melanoma and one each against cervical and gastric carcinoma. Antibody 99-57 stained malignant cells from invasive carcinoma but not normal cervical cells. In cells from intraepithelial neoplasia, staining intensity was highest in severely dysplastic cells. Thus monoclonal antibodies are potentially useful in the detection of malignant cervical cells within a large number of nonmalignant cells, in conjunction with other diagnostic procedures. Topics: Animals; Antibodies, Monoclonal; Binding Sites, Antibody; Cell Differentiation; Female; Humans; Immunoenzyme Techniques; Keratins; Mice; Mice, Inbred BALB C; Uterine Cervical Neoplasms | 1985 |
[Immunohistochemical localization of keratin and secretory component in carcinoma of the uterine cervix].
Carcinoma of the uterine cervix is said to frequently show a combination of squamous epithelial and glandular epithelial characteristics. In the present study, immunohistochemical localization of keratin and secretory component (SC) was studied to clarify these characteristics of cancers of the cervix, and the following results were obtained. Demonstration of the localization of keratin and SC was useful in providing functional markers of the squamous and glandular epithelium of the cervix. In epidermoid carcinomas, the squamous epithelial character of the keratinizing carcinomas was strongest and decreased in the large cell non-keratinizing, followed by the small cell non-keratinizing carcinomas. The glandular character of these lesions decreased in the same order. Subclassification of CIS did not reveal any major changes with either kind of staining. So-called bipotential differentiation was found in 21% of the epidermoid, 53% of the adenocarcinomas and 13% of the CIS. In the clinical stages of epidermoid carcinomas, the stage I and II cases more frequently showed squamous characteristics than did the stage 0 cases. Topics: Adenocarcinoma; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Immunoglobulin Fragments; Keratins; Secretory Component; Uterine Cervical Neoplasms | 1985 |
Adenocarcinoma in situ and invasive adenocarcinoma of the uterine cervix. An immunohistologic study with antibodies specific for several epithelial markers.
The distribution of carcinoembryonic antigen (CEA), secretory component (SC), fat globule membrane antigens ( FGMA ), and keratin was determined immunohistochemically in 22 invasive adenocarcinomas of various types and in 9 adenocarcinomas in situ of the uterine cervix. In the invasive adenocarcinomas 77% were positive for CEA, 47% for SC, 89% for keratin, and 77% for FGMA . In adenocarcinomas in situ 67% were positive for CEA, 11% for SC, and 44% for keratin. The location of the markers was variable in the cells, and the cells in a tumor were irregularly positive. For a given histologic type there were several phenotypes. No correlation was found between histologic types of invasive adenocarcinomas and the various phenotypes. It remains to be shown whether a particular phenotype has a particular biological behavior. The detection in the serum of the markers shown in histologic preparations could be useful in the postsurgical monitoring. Topics: Adenocarcinoma; Adipose Tissue; Adult; Aged; Antigens, Neoplasm; Antigens, Surface; Carcinoembryonic Antigen; Carcinoma in Situ; Carcinoma, Adenoid Cystic; Female; Histocytochemistry; Humans; Keratins; Middle Aged; Radioimmunoassay; Secretory Component; Uterine Cervical Neoplasms | 1984 |
Immunocytochemical localization of keratin in normal, dysplastic and neoplastic cervical epithelium.
The PAP immunocytochemical technique utilizing specific keratin antibody was applied to paraffin sections from 36 cervical biopsies. Normal squamous epithelium and condylomas had similar patterns of keratin production with intense staining of intermediate and upper layers, while basal cells remained negative. Dysplasia, carcinoma in situ and infiltrating squamous carcinoma showed uneven distribution of keratin with the least amount seen in the areas with high mitotic rate and anaplasia. All large cell squamous carcinomas demonstrated presence of significant amounts of keratin. Squamous carcinomas of the small cell type were essentially keratin-free. Topics: Adenocarcinoma; Carcinoma in Situ; Carcinoma, Squamous Cell; Cervix Uteri; Condylomata Acuminata; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms | 1984 |
An immunohistochemical study of the distribution of epithelial antigens in the uterine cervix.
Neoplastic and nonneoplastic tissue from human uterine cervixes was stained immunohistochemically for three epithelial antigens--epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and cytoplasmic keratin. Anti-EMA serum stained four of 21 nonneoplastic cases and all cases of cervical intraepithelial neoplasia (CIN) (25) and invasive carcinoma (16); CEA was positive in six of ten of the nonneoplastic specimens, 19 of 23 CIN specimens, and six of seven invasive carcinomas tested. Cytoplasmic keratin did not survive fixation in formal saline and for this antigen tissue had to be fixed in methacarn; all the tissues examined were positive. Topics: Antigens; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cervix Uteri; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Protein Precursors; Uterine Cervical Neoplasms | 1983 |
Squamous cell carcinoma with sarcoma-like stroma of the female genital tract. Clinicopathologic study of four cases.
Four cases of squamous cell carcinoma with sarcoma-like stroma located in the vulva (1), vagina (2) and cervix (1) of postmenopausal women are presented. The gross and microscopic features are very similar to those of similarly named tumors occurring in the upper respiratory and digestive tract and in the skin. Light microscopic, electron microscopic, and immunohistochemical examination provided convincing evidence that these tumors are composed solely of squamous cell carcinoma, which has undergone a spindle cell sarcoma-like transformation in the deeper portions. Follow-up revealed an aggressive clinical course in three of the four patients, who died of their tumor between 2 and 45 months after presentation. At the time of death, two of the patients had widespread metastases and the other had massive local recurrence. Topics: Aged; Carcinoma, Squamous Cell; Carcinosarcoma; Diagnosis, Differential; Female; Fibroma; Follow-Up Studies; Genital Neoplasms, Female; Histocytochemistry; Humans; Keratins; Middle Aged; Sarcoma; Uterine Cervical Neoplasms; Vaginal Neoplasms; Vulvar Neoplasms | 1983 |
Cytokeratins of normal epithelia and some neoplasms of the female genital tract.
Cytokeratins are a family of polypeptides of intermediate filaments which in diverse epithelia are expressed in different, yet specific, combinations. We have studied the cytokeratins present in normal epithelia of the female genital tract, in comparison with those present in genital tract carcinomas, by two-dimensional gel electrophoresis of cytoskeletal proteins from microdissected tissues and by immunofluorescence microscopy. Cells of ovarian mesothelium, oviduct, endometrium, and endocervix contain cytokeratin polypeptides nos. 7, 8, 18, and 19. By contrast, tonofilaments of the stratified squamous epithelia of vagina and exocervix contain cytokeratins 4, 5, 6, 13, 14, 15, 16, and 19. Exocervical regions distant from the endo-exocervical junction as well as vagina contain, in addition, the large (Mr 68,000) and basic cytokeratin component no. 1, previously described in epidermis. Endocervical squamous metaplasia at the endo-exocervical border displays a complex cytokeratin pattern, probably due to cell-type heterogeneity. Similar cytokeratin patterns are also observed in genital tract epithelia of the cow and mouse. In human carcinomas of the female genital tract, two main types of cytokeratin patterns can be distinguished. Ovarian carcinomas and endometrial adenocarcinomas express cytokeratins 7, 8, 18, and 19 and, thus, maintain the pattern of the cells of their origin. In endocervical adenocarcinomas the additional presence of component no. 17 has been noted. Nonkeratinizing squamous cell carcinomas of the cervix show a very complex pattern (cytokeratins 5, 6, 7, 8, 13, 14, 15, 17, 18, and 19). Keratinizing squamous cell carcinomas of the cervix display lower complexity and lack cytokeratins 7, 8, and 18. When frozen sections are examined by immunofluorescence microscopy, all epithelia of the genital tract are stained with the monoclonal cytokeratin antibody KG 8.13. Simple epithelia but not the stratified epithelia of vagina and exocervix also react with monoclonal antibodies specific for cytokeratins 8 or 18. The value of cytokeratin polypeptide patterns in distinguishing diverse epithelial cell types of the female genital tract, in elucidating the histogenesis of neoplasms, and in providing a new tool for the differential diagnosis of tumors is discussed. Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cattle; Epithelium; Female; Genital Neoplasms, Female; Genitalia, Female; Humans; Keratins; Mice; Uterine Cervical Neoplasms | 1983 |
Adenoid cystic carcinoma of the uterine cervix: ultrastructure, immunofluorescence, and criteria for diagnosis.
An example of adenoid cystic carcinoma of the cervix was recently encountered in our laboratory and studied by histochemistry, electron microscopy, and immunofluorescence in order to compare the neoplasm with adenoid cystic tumors at other sites and to establish criteria for diagnosis. Histochemically, cervical adenoid cystic carcinoma showed the two types of mucin, epithelial and stromal, as expected in adenoid cystic carcinomas of other organs. Ultrastructurally, this tumor was characterized by redundant basal lamina forming pseudocysts, intercellular spaces, and occasional true lumens with microvilli. Immunofluorescence studies showed that the cells contain at least two antigenically different types of filaments, actin and keratin, and that the cells produce true basement membrane (collagen IV). The presence of actin suggests myoepithelial differentiation even though the tumor probably originated from the cervical reserve cells, and myoepithelium is not a known component of normal cervix. This study shows that cervical adenoid cystic carcinoma is a distinct entity which can be identified and separated from other types of cervical adenocarcinomas. Topics: Actins; Aged; Carcinoma, Adenoid Cystic; Collagen; Female; Fluorescent Antibody Technique; Histocytochemistry; Humans; Keratins; Microscopy, Electron; Neoplasm Proteins; Uterine Cervical Neoplasms | 1982 |
Carcinoma of the cervix: the effect of age on survival.
Topics: Adult; Age Factors; Aged; Female; Humans; Keratins; Middle Aged; Pregnancy; Pregnancy Complications; Texas; Uterine Cervical Neoplasms | 1980 |
Histologic classification, lymph node metastases, and patient survival in stage IB cervical carcinoma: an analysis of 245 uniformly treated cases.
Topics: Carcinoma; Female; Humans; Keratins; Lymphatic Metastasis; Prognosis; Time Factors; Uterine Cervical Neoplasms | 1978 |
[Comparison of cytological features in keratinizing dysplasia and keratinizing squamous carcinoma (author's transl)].
By means of the literature pathological aspects of the keratinizing dysplasia and the keratinizing squamous cell carcinoma are discussed. It has been tried to point out cytological criterias by means of which a differential diagnosis can be performed between the two lesions. The difficulties of this task are mentioned. To give examples for the diagnostic criterias pictures of our own material are demonstrated. Criterias for differential diagnosis of the two lesions are summarized in a table. By the use of all criterias mentioned above a differential diagnosis can be performed cytologically in most cases. Cytological findings should be described as precisely as possible. It is only in this way that the best information can be given to the clinician referring to diagnostical or therapeutical procedures that should be performed further on. Topics: Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears | 1978 |
Histological cell type and DNA value in the prognosis of squamous cell cancer of uterine cervix.
Based on the evaluation of 362 cases of squamous cell carcinoma of the uterine cervix, the distribution of the tumours in relation to their modified Broders' grade, histological cell type as proposed by Wentz and Reagan, and the clinical stage of disease was evaluated. The morphological characteristics of the 3 cell types-large cell non-keratinizing, keratinizing, and small cell cancers-were described. The 5 year survival in relation to Broders' grade, cell type, extent and DNA values of the malignant cells were evaluated and compared. Broders' grading system was not useful in predicting the biological behaviour of cervical squamous cancer. The histological cell type and extent of the tumour were important factors in prognosis. The 5 year survival for large cell cancer was 51·8%, keratinizing cancer 34·7% and small cell cancer 10·0%. The 5 year survival was 63·3% for stage I neoplasms, 52·9% for stage II neoplasms, 30·7% for stage III neoplasms and 15·0% for stage IV neoplasms. When the DNA values of neoplastic cells were considered in relation to cell type and extent of disease, the biological behaviour of cervical squamous cell cancers was determined more accurately. The 5 year survival of women with cervical cancer in which the DNA values of the neoplastic cells exceeded 155 was more favourable than those with DNA values of less than 155. This difference in 5 year survival was evident for comparable cell type and clinical stage of disease. Topics: Adult; Age Factors; Aged; Carcinoma, Squamous Cell; DNA, Neoplasm; Female; Humans; Keratins; Lymphocytes; Middle Aged; Prognosis; Uterine Cervical Neoplasms | 1973 |
Keratin granulomas in irradiated squamous cell carcinoma of various sites.
Topics: Adult; Aged; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Granuloma; Humans; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Radium; Skin Diseases; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms | 1966 |
[KERATINIZATION AND REGRESSIVE CHANGES IN CANCER OF THE CERVIX].
Topics: Electrons; Female; Humans; Keratins; Microscopy; Microscopy, Electron; Neoplasms; Pathology; Uterine Cervical Neoplasms | 1964 |