bromochloroacetic-acid and Carcinoma--Medullary

Topics: Aged; Carcinoma, Medullary; Carcinoma, Squamous Cell; Diagnosis, Differential; Gastrectomy; Humans; Keratins; Lymphoma; Melanoma; Middle Aged; Neoplasm Staging; Retrospective Studies; RNA, Viral; Stomach Neoplasms

To investigate the clinicopathological features, histogenesis and prognosis of mucinous tubular and spindle cell carcinoma (MTSCC).. Five MTSCCs were studied with histochemical, immunohistochemical staining, electron microscopy, and review of the related literatures.. Four cases of MTSCC were females and one was male. Three patients presented with flank discomfort and two were incidentally found with health examination. In gross examination, the tumors were circumscribed. The cut surface was solid, gray-white, yellow or red. Necrosis was present in one case of high-grade MTSCC. Microscopically, low-grade MTSCC was mainly consisted of tubular, spindle cell and mucinous stroma with relatively bland morphology, and mitoses were rare. While in the high-grade area of one case, the cells were spindle or polymorphic with severe atypia and high mitotic activity, without mucinous stroma and tubular structure. Mucin was positive for Alcian blue. The neoplastic cells were positive for vimentin (5/5), CKpan (5/5), CK7 (5/5), CK19 (5/5), 34betaE12 (1/5), EMA (5/5), E-cadherin (3/5), CD10 (1/5), P504S (5/5), and CAM5.2 (5/5). The Ki-67 index was low (< or = 5%) in the low-grade component, while it was high (15%) in the high-grade component. Ultrastructural study showed short microvilli along glandular lumens. The nuclear membrane was focally invaginated. Four cases were followed up for 3 to 52 months, and recurrence and metastasis were not found.. MTSCC occurs predominantly in females and it is a rare kidney neoplasm. Most of MTSCCs are low-grade and the prognosis is relatively good. However, the patients of high-grade MTSCC should be closely followed up.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Carcinoma; Carcinoma, Medullary; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Keratins; Kidney Neoplasms; Leiomyosarcoma; Male; Middle Aged; Mucin-1; Nephrectomy; Racemases and Epimerases; Vimentin

To study epithelial mesenchymal transition (EMT) in breast cancer, molecules such as PRL-3, Snail, Cytokeratin and Vimentin involved in EMT were evaluated.. In this study, m-RNA expression of PRL3 and Snail by RT PCR, protein expression of PRL-3, Snail, Cytokeratin and Vimentin by immunohistochemistry were evaluated on paraffin-embedded tissue sections of 100 patients with breast cancer.. PRL3 m-RNA expression (above cut off level > 2487301.00) and PRL-3 protein expression was noted in 52% and 70% of breast carcinoma patients, respectively. The higher incidence of PRL3 protein than m-RNA expression could be due to post translation modification. Further, Snail m-RNA expression (above cut off level > 1285142.00) and Snail protein expression was noted in 53% and 54% of breast cancer patients respectively and Snail protein expression was found significantly higher in patients with pre-menopausal status. The loss of cytokeratin expression in 32% and gain of vimentin expression in 17% was noted in these patients. Vimentin expression was found significantly higher in patients with stage IV disease, BR score 4 and PR negativity. In multivariate survival analysis, Vimentin expression found as strong indicator of biologically aggressive breast cancer predicting reduced disease free survival (DFS) and overall survival (OS).. In our study reveals that Vimentin expression emerged as significant biomarker for predicting reduced DFS and OS in breast cancer. The study proposes routine evaluation of Vimentin with other predictive parameters can allow use of EMT inhibitors with conventional therapy to revert EMT in breast cancer.

Topics: Adenocarcinoma, Mucinous; Adult; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Medullary; Carcinoma, Papillary; Disease-Free Survival; Epithelial-Mesenchymal Transition; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Middle Aged; Neoplasm Grading; Neoplasm Proteins; Neoplasm Staging; Prognosis; Protein Tyrosine Phosphatases; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Snail Family Transcription Factors; Transcription Factors; Vimentin

Topics: Aged; Carcinoma, Medullary; Epstein-Barr Virus Infections; Gastric Mucosa; Gastroscopy; Humans; Immunohistochemistry; Keratins; Male; Stomach Neoplasms; Ultrasonography

Cytokeratin (CK) immunohistochemistry can play an important role in breast carcinoma evaluation. We evaluated the expression of a panel of commonly used CKs in a large cohort of breast cancers and assessed its correlation with other biomarkers and breast cancer subtypes. Expression of CK7, CK8, CK18 and CK19 was observed in more than 90 % of all breast carcinomas in this study, confirming their efficacy in immunohistochemical identification of breast cancer. A combination of CK8 and CK7 gave the highest sensitivity for detection of a minute number of breast cancer cells. Expression of other CKs, including CK5/6, CK14 and CK20, correlated positively with high tumour grade. The expression of CK5/6 and CK14 in a significant number of high-grade tumours raised concern regarding the use of absence of their expression to identify breast carcinoma. For identification of the basal subtype, CK5/6 gave a higher detection rate than CK14. CK20 expression was found more frequently than reported in previous studies, might constitute an indicator of poor prognosis and may be associated with the molecular apocrine subtype. This study highlights the diagnostic and prognostic relevance of the unique CK expression patterns in breast cancer.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Medullary; Cohort Studies; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Prognosis; Tissue Array Analysis; Young Adult

Basal-like carcinomas and human epidermal growth factor receptor 2 (HER-2/neu) overexpression carcinomas are the subgroups of breast cancers that have the most aggressive clinical behavior. Phosphorylation/activation of c-Jun NH2-terminal kinase is characterized as a stress-activated protein kinase, which regulates apoptosis after cellular stress. The aim of this study was to evaluate the association of phosphorylated c-Jun NH2-terminal kinase expression with phenotypes and clinicopathologic parameters of breast cancer. Phosphorylated c-Jun NH2-terminal kinase was immunohistochemically measured in a cohort of 160 patients with invasive breast cancer treated with therapeutic surgery followed by anthracycline or docetaxel-based chemotherapy. These results were further correlated with the phenotypes and clinicopathologic characteristics of breast cancers. Increased phosphorylated c-Jun NH2-terminal kinase expression was significantly associated with lack of estrogen receptor expression (P < .0001), positivity for cytokeratins 5/6 (P = .029), epidermal growth factor receptor (P = .035), basal-like phenotype (P = .015), and "triple-negative" phenotype (P = .01). Furthermore, the positive expression of phosphorylated c-Jun NH2-terminal kinase was positively correlated with p-glycoprotein (r = 0.54, P < .0001) and multidrug resistance-associated protein 1(r = 0.38, P < .0001) but not with lung resistance protein (r = -0.02, P = .78). Our results indicate that the activation of phosphorylated c-Jun NH2-terminal kinase may play a role in the carcinogenesis of basal-like and triple-negative breast carcinoma.

Topics: Adenocarcinoma, Mucinous; ATP Binding Cassette Transporter, Subfamily B, Member 1; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Medullary; Chi-Square Distribution; Epidermal Growth Factor; Estrogen Receptor alpha; Female; Humans; Immunohistochemistry; JNK Mitogen-Activated Protein Kinases; Keratins; Multidrug Resistance-Associated Proteins; Neoplasm Staging; Patient Selection; Phosphorylation; Up-Regulation; Vault Ribonucleoprotein Particles

Topics: Carcinoma, Medullary; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Keratins; Kidney Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasms, Squamous Cell; Nephrectomy; Radiotherapy, Adjuvant

Medullary carcinoma and serrated adenocarcinoma are two variants of colon cancer which are associated to particular pathways. Medullary carcinoma is invariably associated with MSI while serrated adenocarcinoma is characterized by excess of methylation. TNM classification and the tumoral grade are still the most important prognostic factors. Several parameters including morphological criteria, molecular features or immunohistochemical markers seem to be relevant but none of them are today used in clinical practice. A more accurate approach of the evaluation of these additional parameters should improve their prognosis values. double dagger.

Topics: Adenocarcinoma; Carcinoma, Medullary; Colorectal Neoplasms; DNA Mismatch Repair; Humans; Inflammation; Keratins; Neoplasm Invasiveness; Prognosis

Triple-negative breast carcinoma accounts for approximately 15% of all breast cancers. It is characterized by an aggressive clinical history, high rate of local relapse, and association with the basal epithelial-like subtype. Variations in breast cancer subtype and clinical outcome often exist across racial and ethnic lines. Therefore, the aim of this study was to compare the immunohistochemical and clinicopathologic characteristics of triple-negative breast carcinoma in women living in Vietnam with those from the United States. Invasive triple-negative breast carcinoma of patients from the 2 populations was characterized by tissue microarray for the expression of basal cytokeratins (CK5/6, CK7, CK14), luminal cytokeratins (CK8, CK18, CK19), and markers associated with the basal phenotype (cKit, epithelial growth factor receptor, P-cadherin, p53, and p63). Significant differences in expression between the 2 populations were not observed for the basal cytokeratins. However, epithelial growth factor receptor and P-cadherin, markers associated with the basal phenotype, were underexpressed in Vietnamese patients. Of the luminal cytokeratins, CK8 was overexpressed and CK18 was underexpressed in the Vietnamese women. Significant differences were also observed regarding the clinicopathologic characteristics. Triple-negative breast carcinoma in Vietnamese women was smaller and less likely to be grade III. In addition, it was more frequently of ductal histologic type and less often medullary or metaplastic. These differences in histology and marker expression suggest that triple-negative breast carcinoma has unique biological characteristics in women from Vietnam and the United States, and may follow a unique clinical course in each of the 2 populations.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Medullary; Female; Humans; Keratins; Middle Aged; Neoplasm Staging; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Tissue Array Analysis; United States; Vietnam

Topics: Anion Exchange Protein 1, Erythrocyte; Biomarkers; Carcinoembryonic Antigen; Carcinoma, Medullary; Carcinoma, Transitional Cell; Child; Diagnosis, Differential; Female; Humans; Keratins; Kidney Neoplasms; Kidney Tubules, Collecting; Mucin-1; Nephrectomy; Rhabdoid Tumor; Vimentin

We report seven cases of renal medullary carcinoma collected from several institutions in Brazil. In spite of a relatively high incidence of sickle cell trait in Brazil, this is a rare tumor. All patients were males between the ages of 8 and 69 years (mean 22 years). From the collected information, the most frequent presenting symptoms were gross hematuria and flank or abdominal pain. The duration of symptoms ranged from 1 week to 5 months. Most of the tumors were poorly circumscribed arising centrally in the renal medulla. Size ranged from 4 to 12 cm (mean 7 cm) and hemorrhage and necrosis were common findings. All seven cases described showed sickled red blood cells in the tissue and six patients were confirmed to have sickle cell trait. All cases disclosed the characteristic reticular pattern consisting of tumor cell aggregates forming spaces of varied size, reminiscent of yolk sac testicular tumors of reticular type. Other findings included microcystic, tubular, trabecular, solid and adenoid-cystic patterns, rhabdoid-like cells and stromal desmoplasia. A peculiar feature was suppurative necrosis typically resembling microabscesses within epithelial aggregates. The medullary carcinoma of the 69-year-old patient was associated with a conventional clear cell carcinoma. To our knowledge, this association has not been previously reported and the patient is the oldest in the literature. The survival after diagnosis or admission ranged from 4 days to 9 months. The 8-year-old African-Brazilian patient with a circumscribed mass is alive and free of recurrence 8 years after diagnosis. This case raises the question whether a periodic search for renal medullary carcinoma in young patients who have known abnormalities of the hemoglobin gene and hematuria could result in an early diagnosis and a better survival.

Topics: Abdominal Pain; Adolescent; Adult; Aged; Brazil; Carcinoembryonic Antigen; Carcinoma, Medullary; Child; Flank Pain; Hematuria; Humans; Immunohistochemistry; Keratins; Kidney Medulla; Kidney Neoplasms; Male; Mucin-1; Neoplasm Metastasis; Risk Factors; Sickle Cell Trait; Time Factors; Treatment Outcome; Vimentin

Topics: Aged; Carcinoma; Carcinoma, Medullary; CD5 Antigens; Cell Differentiation; Choristoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Thymoma; Thymus Gland; Thyroid Gland; Thyroid Neoplasms

Medullary breast cancer (MBC) is a rare, diagnostically difficult, pathological subtype. Despite being high grade, it has a good prognosis. MBC patients have an excess of BRCA1 germ-line mutation and reliable identification of MBC could help to identify patients at risk of carrying germline BRCA1 mutations or in whom chemotherapy could be avoided. The aim of this study was therefore to improve diagnosis by establishing an MBC protein expression profile using immunohistochemistry (IHC) on tissue-microarrays (TMA). Using a series of 779 breast carcinomas ('EC' set), diagnosed initially as MBC, a double-reading session was carried out by several pathologists on all of the histological material to establish the diagnosis as firmly as possible using a 'medullary score'. Only MBCs with high scores, i.e. typical MBC (TMBC) (n=44) and non-TMBC grade III with no or low scores (n=160), were included in the IHC study. To validate the results obtained on this first set, a control series of TMBC (n=17) and non-MBC grade III cases (n=140) ('IPC' set) was studied. The expression of 18 proteins was studied in the 61 TMBCs and 300 grade III cases from the two sets. The global intra-observer concordance of the first reading for the diagnosis of TMBC was 94%, with almost perfect kappa (kappa) of 0.815. TMBC was characterized by a high degree of basal/myoepithelial differentiation. In multivariate analysis with logistic regression, TMBC was defined by the association of P-cadherin (R=2.29), MIB1 > 50 (R=3.80), ERBB2 negativity (R=2.24) and p53 positivity (RR=1.45).

Topics: Breast Neoplasms; Cadherins; Carcinoma, Basal Cell; Carcinoma, Medullary; Cell Transformation, Neoplastic; Female; Gene Expression Regulation, Neoplastic; Genes, BRCA1; Genes, erbB-2; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Mutation; Neoplasm Proteins; Phenotype; Protein Array Analysis; Tumor Suppressor Protein p53

There has been much recent investigation of the cyclooxygenase (Cox) enzymes in tumor biology, but, to our knowledge, no study has yet been published describing Cox activity in medullary carcinoma of the thyroid (MTC). Nine cases of MTC from the past 10 yr were retrieved from our hospital archives. Slides cut from formalin-fixed paraffin-embedded tumor tissue from these cases were assessed for the activities of Cox-1 and Cox-2 enzymes by immunohistochemistry as well as by a battery of immunohistochemical stains for intermediate filaments, peptide hormone, and proliferation and promoter antigens. The staining reactions were semiquantitatively assessed and scored for comparison with each other as well as with each patient s clinical presentation and course. Staining for Cox-1 and Cox-2 enzymes was present only in tumorous tissue, not in nontumorous thyroid tissue or C-cells. Cox-2 staining was not consistently increased over Cox-1 staining; however, Cox-2 staining bore statistically significant correlations with the expression of low molecular weight keratin, thyroid-transforming factor-1, topoisomerase, and MIB1. Hyperplastic C-cells from patients with diverse physiologic conditions and from three patients with C-cell hyperplasia accompanying medullary carcinoma or multiple endocrine neoplasia type IIa showed no reactivity for the Cox antibodies. It appears that Cox enzyme immunoreactivity is present only in the neoplastic C-cells of medullary carcinoma, but with variable expression. A practical application of the preceding finding might involve the use of Cox staining to distinguish invasive medullary carcinoma cells from hyperplastic C-cells.

Topics: Adult; Carcinoma, Medullary; Cyclooxygenase 1; Cyclooxygenase 2; DNA Topoisomerases; Female; Humans; Immunohistochemistry; Isoenzymes; Keratins; Ki-67 Antigen; Male; Membrane Proteins; Middle Aged; Nuclear Proteins; Prostaglandin-Endoperoxide Synthases; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors

Topics: Adult; Biomarkers, Tumor; Carcinoma, Medullary; Chorionic Gonadotropin, beta Subunit, Human; Fatal Outcome; Female; Hematuria; Humans; Keratins; Kidney Neoplasms; Mucin-1; S100 Proteins; Sickle Cell Trait

To assess the potential value of cytokeratins (CK) 8,18,19 as tumor markers for thyroid diseases, a study was performed comparing serum CK 8,18,19 levels in patients affected from thyroid carcinoma, adenoma, other benign thyroid diseases and healthy volunteers as controls. One hundred cases (65 patients and 35 controls) were examined. Thirty patients had thyroid carcinoma (18 papillary--PTC, 8 follicular--FTC, 4 medullary--MTC), 19 non-toxic goiter, 10 thyroid adenoma, 6 chronic thyroiditis and 35 healthy volunteers as controls. These controls were matched by age and sex. The mean value of CK in benign thyroid diseases (46.1 U/L) was significantly higher (p<0.02) than that in healthy controls (29.6 U/L). The mean value of CK in carcinomas (68.1 U/L) was significantly higher than that in healthy controls (p<0.01) and benign thyroid diseases patients (p<0.05). The positive rate of CK in thyroid carcinomas was 28.1%, while in benign thyroid diseases was 17.8%. The CK sensitivity for thyroid carcinomas was 28.1%, with a specificity of 80% and accuracy of 70.4%. In PTC patients the mean CK value was not significantly higher than in the benign diseases' group and in healthy subjects. No evident correlation between CK levels and tumor mass was found. In FTC patients the mean value was significantly higher than in the benign diseases' group and in healthy subjects. Large tumors showed the highest levels, while small tumor values were similar to the control ones. In MTC patients the mean value was significantly higher than in the benign diseases' group and in healthy subjects, with the highest peaks in large tumors and metastatic tumors. The detection of increased values in thyroid carcinomas with high metastatic potential (FTC and MTC) seems to confirm the role of these antigens in predicting the malignancy's degree of the neoplasm. These findings, if confirmed in larger series, could play an important role in assessing the CK 8,18,19 serum level as a real prognostic factor. Further repeated serum determinations after total thyroidectomy might indicate the role of CK 8,18,19 as serum markers predicting the risk of metastases.

Topics: Adenocarcinoma, Follicular; Adenoma; Biomarkers, Tumor; Carcinoma, Medullary; Carcinoma, Papillary; Cell Differentiation; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Thyroid Neoplasms

The cytokeratin (CK) phenotype and vimentin expression of 31 medullary carcinomas was studied using commercially available antibodies on archived material. Comparing the phenotype of typical and atypical tumours and the phenotype of metastases, the biological significance of cytokeratin and vimentin expression in medullary carcinomas of the breast was determined.. Antibodies to CK4, CK5 and 6, CK7, CK14, CK8 and 18, CK19, CK20 and to vimentin were used. All the typical and atypical medullary carcinomas and the metastases (10 cases) stained negatively for CK4 and positively for CK8-18 (CAM5.2). Almost all the tumours were CK7 and CK19 positive and CK20 negative. Twelve per cent of the tumours contained CK14. Twenty-five per cent of the typical, 43% of the atypical and 20% of the metastatic medullary carcinomas showed CK5-6 positivity. No association between the cytokeratin-vimentin profile of the tumours and axillary node metastases, tumour size or oestrogen receptor status was found but instability of CK expression was demonstrated by comparing the primary tumours with their metastases.. : Medullary carcinomas of the breast express all the glandular type CKs including CK19 and additionally a proportion of the tumours expresses some of the CKs typical for myoepithelial cells. There was no correlation with prognostic factors.

Topics: Breast Neoplasms; Carcinoma, Medullary; Female; Humans; Immunohistochemistry; Keratins; Neoplasm Metastasis; Protein Isoforms

Topics: BRCA1 Protein; Breast Neoplasms; Carcinoma, Medullary; Female; Humans; Immunohistochemistry; Keratins; Mutation

Metastatic adenocarcinomas of unknown primary site are a common clinical problem. Invasive ductal carcinomas of the breast and some special types of invasive breast carcinoma are common sources of metastases. Immunohistochemical algorithms, such as a combination of cytokeratins 20 and 7, can be helpful in this situation. Detailed phenotyping of the different types and subtypes of primary invasive carcinomas and their metastases is an essential prerequisite for a successful search for an unknown primary tumor. A series of 123 primary invasive breast adenocarcinomas of special type and of 27 lymph node metastases was analyzed. Sections of selected blocks were stained with two monoclonal cytokeratin antibodies (CK20 and CK7) and evaluated as negative (no staining), focally positive or diffusely positive. Of the 123 carcinomas, 113 (92%) proved to be CK20 negative. Three of 82 (4%) invasive lobular carcinomas, three of 11 (27%) mucinous carcinomas, one of 10 (10%) tubular carcinomas, and one invasive papillary carcinoma stained diffusely with CK20. Additionally, a tubulolobular carcinoma and a medullary carcinoma showed focal CK20 positivity. One hundred twenty (98%) of the 123 tumors were CK7 positive, five of them only focally. One of the four solid invasive lobular carcinomas, one medually carcinoma, and one invasive papillary carcinoma were completely negative for CK7. Only two cases, one mucinous and one invasive papillary carcinoma, exhibited the CK20(+)/CK7(-) ("colorectal") pattern. One of the lymph node metastases was CK20(+); another was CK7(-). Like their ductal counterparts, invasive breast carcinomas of special type are usually CK20(-)/CK7(+); they generally retain this phenotype in their metastases. However, there are CK20-positive special-type breast carcinomas that can be confused with gastrointestinal or pancreaticobiliary carcinoma in metastases, especially if they are mucinous or invasive lobular.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Breast Neoplasms; Carcinoma, Medullary; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasm Invasiveness; Tissue Distribution

Permanent human tumor cell lines are an important tool for the study of breast cancer. Two new breast cancer cell lines (BrCa-MZ-01 and BrCa-MZ-02) were isolated from a solid tumor and a pleural effusion, respectively. One cell line was established from a medullary carcinoma, the other from a ductal carcinoma. These cells exhibit ultrastructural and immunohistochemical features of epithelial cells of mammary origin. Intermediate filament and cytokeratin typing showed a clear predominance of the simple-epithelial cytokeratins CK 8, CK 18 and CK 19, although the expression was reduced in comparison to the hormone receptor-positive reference cell lines MCF-7 and ZR-75-1. Both cell lines produced slow-growing tumors after subcutaneous (s.c.) transplantation of 1 x 10(7) viable tumor cells into nude mice. The cell line BrCa-MZ-01 expresses the estrogen and progesterone receptor, whereas the cell line BrCa-MZ-02 remains negative. Both cell lines are positive for secretion of platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta), whereas interleukin-6 (IL-6) is only secreted by the cell line BrCa-MZ-02.

Topics: Aged; Aged, 80 and over; Animals; Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Medullary; Cell Division; Cell Line; Epithelial Cells; Female; Humans; Immunohistochemistry; Interleukin-6; Intermediate Filament Proteins; Keratins; Mice; Mice, Nude; Platelet-Derived Growth Factor; Receptors, Estrogen; Receptors, Progesterone; Transforming Growth Factor beta; Transplantation, Heterologous; Tumor Cells, Cultured

Concurrent medullary and papillary carcinomas of the thyroid gland are rare and occurrence of the medullary and medullary-papillary carcinoma, as far as we know, has not been previously described. The medullary carcinoma was found in the upper part of the right lobe and the mixed medullary-papillary carcinoma in the left lobe of thyroid gland. Immunohistochemistry revealed calcitonin positivity in the medullary parts of the carcinoma and thyroglobulin positivity in papillary structures. Both light microscopy and immunohistochemistry observation distinguished these two cell lineages. The patient was treated with radiotherapy but died 18 months after first symptoms. Metastases were identified in the liver, mediastinal lymph nodes and soft tissues and micro-metastases in the lungs. The authors discuss histogenesis of mixed thyroid carcinomas.

Topics: Biomarkers, Tumor; Calcitonin; Carcinoma, Medullary; Carcinoma, Papillary; Chromogranins; Humans; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Proteins; Neoplasms, Multiple Primary; Thyroglobulin; Thyroid Neoplasms

Sixty breast carcinomas previously indexed as medullary carcinomas over a 24-year-period were reviewed and reclassified according to definitions suggested by Ridolfi et al. as typical medullary carcinoma, atypical medullary carcinoma, and non-medullary carcinoma. Paraffin sections of tumour tissue were examined by an avidin-biotin complex method using two keratin 19-specific monoclonal antibodies (BA17, DAKO and clone 170-2-14, Boehringer) and a monoclonal oestrogen receptor antibody (DAKO). For comparison 52 ductal carcinomas of grade II and grade III were immunostained as well. The results showed that all 60 tumours with medullary features and all 52 ductal carcinomas reacted moderately to strongly positive with anti-keratin 19 (Boehringer). The staining was diffuse in all cases, except one case of ductal carcinoma (grade III), which stained focally. Immunostaining with the second keratin 19 antibody (BA17) revealed similar results with positive staining in 59 (95%) cases of carcinomas with medullary features and 51 (98%) cases of ductal carcinomas. Only one case in each group did not express keratin 19 (BA17), one re-classified case of non-medullary carcinoma with neuroendocrine features and one case of ductal carcinoma of grade III. None of the 13 cases of typical medullary carcinoma were oestrogen receptor positive and only seven (12%) of the carcinomas with medullary features (2 atypical, 5 non-medullary) were oestrogen receptor positive with quantitative values from 20 to 100%. The 52 ductal carcinomas of grade II and III were oestrogen receptor positive in 56% and 47% of cases. It is concluded that keratin 19 staining is of no particular value in differentiating medullary from poorly differentiated ductal carcinoma. A carcinoma with positive oestrogen receptor staining is not likely to be a typical medullary carcinoma.

Topics: Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Medullary; Female; Humans; Immunohistochemistry; Keratins; Receptors, Estrogen; Staining and Labeling

Using 8 different monoclonal antibodies, immunohistology was performed on 36 follicular adenomas and on 28 follicular, 34 papillary, 27 medullary and 29 anaplastic carcinomas of the thyroid. The panel of antibodies was directed against broad-spectrum cytokeratins (pan-CK, antibody lu-5), against basic and acid high-molecular-weight CK of types #1, 5, 10 and 14, against basic (#5 and 6) and acid high-molecular-weight CK (#13) and against basic (#7 and #8) and acid low-molecular-weight CK (#19 and #20). With the exception of a large number of anaplastic carcinomas, nearly all other tumours exhibited strong immunoreactivity with antibodies against pan-CK, CK 8 and CK 19. CK 20 expression was exclusively shown for 2 medullary carcinomas. Reactivity for high-molecular-weight CK could only, each time focally, be demonstrated for 14 papillary and 2 follicular carcinomas and for 2 anaplastic carcinomas with partial squamous differentiation. Thirteen anaplastic carcinomas were not decorated by any of the CK antibodies applied. CK 7 staining exceeding the staining of individual cells was observed in 26 papillary cancers. In contrast, such a finding could only be obtained with each one follicular adenoma, medullary carcinoma and anaplastic carcinoma and with 5 follicular carcinomas. These results confirm earlier studies in that CK 20 expression among thyroid tumours is restricted to the neuroendocrine medullary carcinomas and that in a larger percentage of anaplastic thyroid carcinomas an epithelial phenotype can not be demonstrated even upon using broad-spectrum CK antibodies. New is the finding that there exist considerable differences between papillary carcinomas and all other non-papillary thyroid tumours regarding CK 7 expression. This result might be of differential diagnostic value for the distinction of follicular and papillary thyroid neoplasias which sometimes have an overlapping histological pattern.

Topics: Adenocarcinoma, Follicular; Adenoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma; Carcinoma, Medullary; Carcinoma, Papillary; Diagnosis, Differential; Humans; Keratins; Thyroid Gland; Thyroid Neoplasms

This investigation was aimed at studying the distribution of keratin 19 in various histological types of invasive breast carcinoma and benign breast lesions using two different antibodies, comparing the results, and assessing the significance of the finding. In particular, the usefulness of using the absence of keratin 19 immunostaining as a marker for medullary carcinoma was examined. Paraffin sections of 49 invasive breast carcinomas and 40 benign lesions were examined by the avidin-biotin complex immunoperoxidase technique using two commercially available keratin 19-specific monoclonal antibodies, BA17 and RCK 108. The results showed that the latter antibody stained more cases and the intensity of its staining was more pronounced than BA17. Most medullary and poorly differentiated invasive ductal carcinomas were BA17 negative and RCK108 negative or weakly positive. Moderately and well-differentiated ductal, invasive lobular, tubular, and most mucinous carcinomas were mostly positive with both antibodies, whereas a case of signet ring and a case of spindle cell carcinoma were negative with the two antibodies. Thirty eight of the 40 benign lesions examined showed variable numbers of positive cells, reflecting in general the pattern seen in normal ducts and acini. It is concluded that although keratin 19 seems to be completely absent or at most only weakly represented in paraffin sections of medullary carcinoma, similar reactions are obtained with poorly differentiated ductal tumors. Different antibodies may give different reactions, but well-differentiated ductal and invasive lobular tumors are usually more strongly stained, whereas signet ring and spindle cell carcinomas seem to be negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Biomarkers, Tumor; Breast Diseases; Breast Neoplasms; Carcinoma, Medullary; Female; Humans; Keratins; Paraffin Embedding

Topics: Amyloid; Animals; Calcitonin; Carcinoma, Medullary; Female; Immunohistochemistry; Keratins; Phosphopyruvate Hydratase; Sheep; Sheep Diseases; Synaptophysin; Thyroglobulin; Thyroid Gland; Thyroid Neoplasms; Vimentin

Solid cell nests of the thyroid gland were studied in 44 patients with medullary thyroid carcinoma. In 10 (22.7%) patients, solid cell nests were revealed in the vicinity of tumour foci (five cases) or in the contralateral thyroid lobe and isthmus (four cases); in one case the location was indeterminate. In all seven cases in which immunohistochemical studies were carried out, solid cell nests showed negative staining for thyroglobulin, calcitonin and chromogranin A, findings which were distinct from those in medullary thyroid carcinoma. It is therefore suggested that solid cell nests of the thyroid are not precursors of this tumour.

Topics: Adolescent; Adult; Aged; Carcinoembryonic Antigen; Carcinoma, Medullary; Child; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; S100 Proteins; Thyroid Gland; Thyroid Neoplasms

The presence of keratin 19 (K19) was searched for by immunostaining in 16 medullary carcinomas, comprising 12 typical and four atypical cases, in 29 undifferentiated high-grade carcinomas (NOS-HG) with conspicuous lymphoid response and in 12 well differentiated low-grade carcinomas (NOS-LG). The medullary carcinomas were all negative whereas 23 of the high-grade and all 12 low-grade carcinomas expressed K19. Staining for K19 could be of value in the differential diagnosis of these tumours. Furthermore, these findings, with other observations, raise the possibility that medullary carcinoma cells could be linked to precursor cells of the terminal duct lobular units because both populations share several characteristics.

Topics: Breast Neoplasms; Carcinoma; Carcinoma, Medullary; Cytoplasm; Female; Humans; Immunoenzyme Techniques; Keratins; Paraffin Embedding