bromochloroacetic-acid and Nasopharyngeal-Neoplasms

Breast metastases from extra-mammary neoplasms are rare, accounting for less than 2% of breast cancer cases. A 43-year-old female patient presented with a mass in her left breast and swelling in her left axillary region. A histopathological examination of the mass showed enlarged polygonal tumor cells with scant to moderate, eosinophilic to amphophilic cytoplasm and enlarged, hyperchromatic and pleomorphic nuclei with irregular nuclear membranes. An immunohistochemistry (IHC) examination was positive for pan cytokeratin and negative for CK7, CK20, S-100, LCA, HMB45, CD 20, desmin, myogenin, GCFDP-15, transcription factor-1, villin, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. As she was a known case of nasopharyngeal carcinoma, and based on the histopathology ndings and IHC profile, the patient was diagnosed with breast metastasis from NPC. The patient was deceased 3 months after refusing the recommended medical intervention.

Topics: Adult; Biomarkers, Tumor; Breast Neoplasms; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Rare Diseases; Saudi Arabia

The functional role of IKKα in vivo is pretty complicated, largely due to its diverse functions through cell autonomous and non-autonomous manners. In addition, most of the studies on IKKα were derived from animal models, whether these findings hold true in human tumors remain unclear. Here we examined the expression of IKKα in nasopharyngeal carcinoma, which includes non-keratinizing carcinoma and keratinizing squamous cell carcinoma, and lung squamous cell carcinoma with keratinization and non-keratinization. We demonstrated that IKKα expression was almost negative in keratinizing cancer and higher expression of IKKα was found in non-keratinizing cancer, and that IKKα expression correlated with cellular differentiation of tumors in non-keratinizing nasopharyngeal carcinoma. These findings demonstrate that IKKα is diversely expressed in keratinizing and non-keratinizing carcinomas in the same type of cancer.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Cell Differentiation; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; I-kappa B Kinase; Kaplan-Meier Estimate; Keratins; Lung Neoplasms; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Phenotype; Prognosis; Time Factors

The tumor designated by Stout and Murray as "hemangiopericytoma" (HPC) more than 50 years ago continues to represent a source of uncertainty and disagreement among pathologists. In particular, questions exist regarding the synonymity of a hemangiopericytomatous growth pattern--defined by a monomorphic population of compact polygonal or bluntly fusiform cells and a branching stromal vascular pattern with a "staghorn" configuration--and the presence of a reproducible biological entity. It has been shown repeatedly that these same histologic features may be observed at least focally in a diversity of neoplasms, including "true" hemangiopericytomas, synovial sarcomas, mesenchymal chondrosarcomas, infantile fibrosarcomas, malignant fibrous histiocytomas, malignant peripheral nerve sheath tumors, leiomyosarcomas, endometrial stromal sarcomas, solitary fibrous tumors, myofibromas, malignant mesotheliomas, thymomas, sarcomatoid carcinomas, malignant melanomas, and "phosphaturic mesenchymal tumors." Despite their potential sharing of the microscopic attributes in question, such neoplasms have individualistic clinical features and can also be distinguished from one another by specialized pathologic analyses. HPC is "defined" in that context by reactivity for vimentin, with or without CD34 and CD57, but it lacks other immunodeterminants of epithelial, neural, and myogenous differentiation. Paradoxically, this phenotype is indeed associated with the presence of myogenous-type cytoplasmic filaments in ultrastructural evaluations of HPC. Other lesions that may resemble "true" HPC--but which possess dissimilar subcellular and clinical characteristics--include solitary fibrous tumors, hemangiopericytomalike tumors of the sinonasal tract, and "infantile (congenital) hemangiopericytomas." Such observations suggest that the hemangiopericytoma is both a pathologic entity and a morphological pattern, and they emphasize the utility of adjuvant pathologic studies in this diagnostic context.

Topics: Actins; Bone Neoplasms; CD57 Antigens; Diagnosis, Differential; Hemangiopericytoma; Humans; Keratins; Meningioma; Myofibromatosis; Nasopharyngeal Neoplasms; Reticulin; Sarcoma, Synovial; Soft Tissue Neoplasms; Stromal Cells

CYFRA 21-1 (CYFRA) is a newly-developed tumor marker which is useful in evaluating non-small cell lung carcinoma, especially the squamous cell type. The purpose of this study was to assess the clinical value of CYFRA in patients with nasopharyngeal carcinoma (NPC). Serum levels of CYFRA (CIS bio-International, France) were measured in 80 patients with untreated NPC. The histologic diagnosis of all patients was confirmed by biopsy. Twenty two (27.5%) of the tumors were classified as undifferentiated carcinoma, and 58 (72.5%) as squamous cell carcinoma. All patients with malignancy were classified according to the International Union Against Cancer (UICC) TNM classification system. In addition, 77 patients without evidence of neoplasm were included as controls. The cut-off value of CYFRA, determined at the 95th percentile of the standard Gaussian variate of controls, was 2.48 ng/ml. The results show that (1) the mean values of serum CYFRA in patients with NPC were significantly higher than those in the control subjects, (2) the overall diagnostic sensitivity of CYFRA in patients with NPC is 58.75%, (3) there was no significant difference between the CYFRA concentrations in patients with squamous cell carcinoma and those in patients with undifferentiated carcinoma, and that (4) there was good correlation between CYFRA values and the tumor stage. There is a statistical difference between T1-T2 patients and T3-T4 patients, and between N0 to N1 patients and N2 to N3 patients. Our results suggest that the CYFRA test may have a potential clinical role as a valuable test in patients with NPC.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Humans; Keratin-19; Keratins; Nasopharyngeal Neoplasms; Neoplasm Staging; Normal Distribution; Predictive Value of Tests; Prognosis; Sensitivity and Specificity

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Child; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Prognosis; Radiotherapy; Retrospective Studies; SEER Program; Survival Rate; Time Factors; Young Adult

Nasopharyngeal carcinoma (NPC) is an aggressive disease and tends to involve surrounding tissues, and biomarkers for better management are yet to be identified.. One hundred and fifty tissue samples with NPC diagnosis were were investigated using pan cytokeratin (CK) and epithelial membrane protein 2 (EMP2) antibodies.. Immunohistochemical expression of CK was identified in 144/150 (96%) and of EMP2 in 120/150 (80%).. There is a high loss of EMP2 in NPC, especially high grade examples. Loss of CK expression is also linked to high grade NPC types.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Grading; Prognosis; Retrospective Studies; Young Adult

Nasopharyngeal squamous cell carcinoma (NPSCC) is uncommon in non-endemic regions. Two major histologic subtypes are recognized: keratinizing (K-NPSCC) and nonkeratinizing (NK-NPSCC). We hypothesize that significant differences exist between the 2 in terms of demographic, clinicopathologic, survival, and prognostic features. We aim to show that differentiating between the 2 subtypes is perhaps the most important first step at the time of diagnosis.. Using a retrospective cohort design, the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry was used to extract data on the 2 major subtypes of NPSCC. Frequency, incidence, and relative survival (RS) were analyzed comparatively. Regression analysis was conducted and hazard ratios (HRs) calculated.. A total of 1624 cases were identified: 1234 (76.0%) cases of NK-NPSCC and 390 (24.0%) cases of K-NPSCC. Five-year RS was 60.6% for NK-NPSCC and 40.5% for K-NPSCC. Regression analysis revealed K-NPSCC to be a poor prognostic factor (HR 2.1; 95% confidence interval, 1.8-2.6; p < 0.0001). Other factors associated with a poor prognosis included female gender in K-NPSCC, age greater than 44 years in both groups, and advanced-stage disease at diagnosis. Favorable prognostic factors included Asian/Pacific Islander race, and treatment with radiation therapy. Higher histologic grade did not portend a worse prognosis for either group.. NPSCC remains an uncommon malignancy in the United States. K-NPSCC and NK-NPSCC represent 2 different histologic entities with important clinical differences. K-NPSCC carries a worse overall prognosis when compared to NK-NPSCC.

Topics: Age Factors; Asian People; Carcinoma, Squamous Cell; Cohort Studies; Diagnosis, Differential; Female; Humans; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Native Hawaiian or Other Pacific Islander; Neoplasm Staging; Prognosis; Retrospective Studies; Risk; Sex Factors; Survival Analysis; United States

Nasopharyngeal carcinoma is the predominant tumor type arising in the nasopharynx with cervical lymph nodes present in 60-90% of all cases at the time of presentation. The most frequent pathological varieties include squamous cell carcinoma well-differentiated keratinizing, moderately differentiated non-keratinizing and an undifferentiated type. We present a case of non-keratinizing undifferentiated carcinoma of the nasopharynx with parapharyngeal and middle cranial fossa space involvement in an 18-year-old male who has been admitted in our hospital for recurrent right ear otitis media. Symptoms consisted in mild conductive hearing loss, trigeminal V2 nerve anesthesia, right ear tinnitus, mild dysphagia, mild dysphonia, right hypoglossal nerve paralysis and right Claude Bernard-Horner's syndrome. Clinical examination revealed no lymph node masses, chest X-ray corresponding to a normal thoracic image. Cranial contrast enhanced CT scan showed a non-homogenous mass of 5.4/4.5/5.5 cm from the level of the right rhinopharyngeal wall, extending in the right parapharyngeal space, invading the right middle cranial fossa. Cranial MRI with contrast enhancement revealed a rhino- and parapharyngeal mass of 5.5/4.6/5.3 cm with intracerebral extension in the right cavernous sinus, right internal carotid artery being engulfed by the tumor mass with partial compression. Several lymph node masses of 1.7/1.2 cm were also revealed. We performed rhinopharyngeal biopsy, right tympanotomy and grommet tube insertion. The tissue specimens were processed with routine histological technique. Subsequent immunohistochemical reactions for pan-cytokeratin AE1/AE3 and leukocytes common antigen were performed. The histological examination of routine stained slides showed that malignant tumor cells had a syncytial pattern of growth in a background of small lymphocytes. The positivity of tumor cells for pan-cytokeratin established the final diagnosis of non-keratinizing undifferentiated carcinoma. The age of onset, the clinical signs and symptoms and minimum involvement of lymph nodes represents the particular aspects of the case.

Topics: Adolescent; Carcinoma; Giant Cells; Humans; Keratins; Magnetic Resonance Imaging; Male; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms

Nasopharyngeal carcinoma (NPC) is rare in western countries albeit affected by common and unrelated phenomena: smoking less in men, more in women and immigration from China and North Africa. We studied trends in NPC incidence, tumour morphology, survival and mortality in order to assess progress against this cancer.. A trend analysis was performed with nationwide incidence and survival data (from The Netherlands Cancer registry in 1989-2009), followed by analysis of mortality (data from Statistics Netherlands) covering the period 1970-2009, and calculating estimated percentages of change (EAPC) in both. According to the WHO classification we distinguished keratinizing SCC (WHO-I), differentiated (WHO-IIA) and undifferentiated (WHO-IIB) non-keratinizing carcinoma.. NPC incidence significantly decreased since 1989, especially in males (EAPC 1989-2009: -1.3; 95% CI: -2.5, -0.2) and in patients with keratinizing SCC (WHO-I) (EAPC: -3.6; 95% CI: -5.3, -1.8). By contrast, the incidence of differentiated non-keratinizing tumours (WHO-IIA) significantly increased in the same period (EAPC: 9.6; 95% CI: 5.6, 13.5). One- and three-year relative survival, as an indicator of disease-specific survival increased slightly from 79% to 81% and from 57% to 65% since 1989. NPC mortality significantly decreased since 1970 (EAPC: -1.2; 95% CI: -1.8, -0.5) and more pronounced since 1989 (EAPC: -3.0; 95% CI: -4.3, -1.6).. During the past two decades, the incidence of NPC in The Netherlands decreased mainly by less keratinizing, supposedly smoking-related NPC (WHO-I). However, the incidence of non-keratinizing NPC (WHO-IIA, B) increased, most likely due to EBV infection and thus related to higher immigration levels of people from high-incidence areas.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Squamous Cell; Child; Disease-Free Survival; Emigration and Immigration; Epstein-Barr Virus Infections; Female; Humans; Incidence; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Staging; Netherlands; Registries; Sex Factors; Smoking; Survival Rate; Young Adult

To investigate whether the neoplastic spindle cells in nasopharyngeal carcinoma (NPC) are associated with the process of epithelial-mesenchymal transition (EMT).. We used immunohistochemistry to analyse the expression of cytokeratin, E-cadherin, β-catenin, vimentin, fibronectin, Snail1, Slug and aldehyde dehydrogenase 1 (ALDH1) in 115 cases of NPC in which there were neoplastic spindle cells; in 47 cases a neoplastic squamous cell component was also present. There was no significant difference in the expression of cytokeratin observed in the neoplastic spindle cells (P = 0.644), compared to the squamous component whereas E-cadherin expression was reduced. By contrast, the expression of β-catenin, vimentin, fibronectin, Snail1, Slug and ALDH1 was up-regulated in the spindle cells (all P = 0.000). Furthermore, E-cadherin expression was associated negatively with β-catenin (P < 0.001), vimentin (P < 0.001), fibronectin (P < 0.001), Slug (P < 0.001) and ALDH1 (P < 0.001) in neoplastic spindle cells, but did not correlate with Snail1 expression (P = 0.093).. Our findings demonstrate for the first time that EMT might play an important role in the development of neoplastic spindle cells in NPC.

Topics: Adolescent; Adult; Aged; Aldehyde Dehydrogenase 1 Family; beta Catenin; Biomarkers, Tumor; Cadherins; Carcinoma, Squamous Cell; Disease Progression; Epithelial-Mesenchymal Transition; Female; Fibroblasts; Fibronectins; Humans; Immunohistochemistry; Isoenzymes; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Invasiveness; Retinal Dehydrogenase; Snail Family Transcription Factors; Transcription Factors; Vimentin; Young Adult

Topics: Adenocarcinoma, Papillary; Adult; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Keratin-7; Keratins; Lung Neoplasms; Nasopharyngeal Neoplasms; Nuclear Proteins; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors

We aimed at determining whether the expression of protease-activated receptor 2 (PAR-2) is involved in the progression of nasopharyngeal carcinoma (NPC) and correlated with latent membrane protein 1 (LMP-1), matrix metalloproteinases-9 (MMP9), and angiogenesis of tumor. PAR-2, LMP-1, and MMP9 expressions were detected in 57 biopsies of primary NPC by immunohistochemistry. The presence of Epstein-Barr virus (EBV) was determined using EBER in situ hybridization, and intratumoral microvessels were highlighted by staining endothelial cells for anti-CD34. The correlations with immunostainings and clinicopathological factors, as well as the follow-up data of patients, were analyzed statistically. Strong expression of PAR-2 in 61.4% (35/57) of the biopsies was correlated with extensive lymph node metastasis and advanced stage of NPC. The patients with PAR-2/LMP-1 or PAR-2/MMP9 dual high-expression tumors had a significant worse prognosis than those with single protein high expression and dual low or negative expression tumors (P=0.013 and 0.004, respectively). Angiogenesis in the tumor is related to overall survival of NPC patients (P=0.001), and exhibits strong PAR-2 expression or LMP-1 expression in tumors associated with increased intratumoral microvessel density (P=0.026 and 0.006, respectively). PAR-2 is a possible mediator cooperating with LMP-1 and MMP9 to influence the progression of NPC by inducing angiogenesis and promoting lymph node metastasis.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; China; Cytoskeletal Proteins; Female; Herpesvirus 4, Human; Humans; In Situ Hybridization; Intracellular Signaling Peptides and Proteins; Keratins; LIM Domain Proteins; Lymph Nodes; Lymphatic Metastasis; Male; Matrix Metalloproteinase 9; Middle Aged; Nasopharyngeal Neoplasms; Neovascularization, Pathologic; Prognosis; Receptor, PAR-2; Ribosomal Proteins; RNA-Binding Proteins; Survival Rate; Young Adult

Nasopharyngeal carcinoma (NPC) is one of the common cancers among Chinese living in South China, Taiwan, Singapore, and several other countries or regions in distinct areas. The etiological factors have not been clearly identified yet. So far, no major gene related with hereditary factor has been identified in NPC carcinogenesis; however, some environmental factors, such as consumption of salted fish and long-term exposure to sulfuric-acid vapor, have been tentatively linked to NPC induction, while research has proposed that there is a close association between Epstein-Barr virus (EBV) and NPC pathogenesis. To investigate the relationship between NPC and EBV, we have established ten NPC cell lines. After extensive investigation, we conclude that EBV may establish an infection only in nasopharyngeal neoplastic cells, not in metaplastic epithelial cells, through the IgA receptor (secretory component protein)-mediated endocytosis. Our observations indicate that EBV plays an important role in enhancement of NPC progression, but is involved in neither the initiation nor the promotion of NPC pathogenesis.

Topics: Animals; Cell Line, Tumor; Endocytosis; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Keratins; Nasopharyngeal Neoplasms; Receptors, Fc; RNA, Viral; Terminal Repeat Sequences; Viral Matrix Proteins

To investigate the relationship among nuclear DNA content, nuclear morphology, clinical response, and radiosensitivity in nasopharyngeal carcinoma (NPC) and the suitability of image cytometric analysis of DNA content and nuclear morphology for predicting radiosensitivity of NPC prior to radiotherapy.. Nuclear DNA content and morphology features were detected by image cytometric analysis in 51 biopsy specimens of NPC prior to radiotherapy. The radiotherapeutic effect experienced by the NPC patients was classified as CR (complete response [i.e., complete tumor disappearance]) and PR (partial response [i.e., residual tumor]) according to pathologic analysis of tumor specimens after completion of the scheduled treatment.. The mean DNA index; the percentage of cells with the DNA pattern of 2C, 5C, aneuploidy respectively; the mean nuclear area; the mean nuclear perimeter and the mean nuclear diameter in the CR group were significantly higher than they were in the PR group.. DNA content and nuclear morphometry by image cytometric analysis were significantly correlated with patient outcome and radiosensitivity of NPC. Other measurements of more biomarkers for predicting the radiosensitivity of NPC await further study.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Cell Nucleus; DNA, Neoplasm; Female; Humans; Image Processing, Computer-Assisted; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Staging; Remission Induction; Treatment Outcome

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Hamartoma; Humans; Inflammation; Keratins; Nasal Mucosa; Nasopharyngeal Neoplasms; Papilloma, Inverted; Paranasal Sinus Neoplasms; Polyps; Teratoma

This study examined potential survival differences among nasopharyngeal carcinoma (NPC) patients from various ethnicities in the United States.. A total of 2436 newly diagnosed NPC patients from 1992 to 2002 were analyzed from the population-based Surveillance, Epidemiology, and End Results (SEER) program. Five-year survival rate estimates and Kaplan-Meier survival curves were calculated. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival.. By multivariate analyses, early age of diagnosis, localized stage at presentation (versus distant, HR=0.35; P<0.0001), radiation therapy (versus none; HR=0.48; P<0.0001), undifferentiated non-keratinizing carcinoma (versus keratinizing squamous cell carcinoma; HR=0.67; P<0.0001), and Chinese ethnicity (versus Caucasian; HR=0.78; P=0.0010) were associated with improved survival. Within keratinizing squamous cell carcinoma histology, the survival advantage of Chinese patients remained even after adjustment for other prognostic factors.. The significant survival advantage of Chinese NPC patients within the keratinizing squamous cell carcinoma histology contributed largely to Chinese ethnicity being an independent and favorable prognostic factor for survival in NPC.

Topics: Adolescent; Adult; Aged; Asian People; Carcinoma, Squamous Cell; Child; Child, Preschool; China; Female; Humans; Infant; Infant, Newborn; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Staging; Prognosis; SEER Program; Survival Rate; United States

To establish a hepatic metastatic subline of nasopharyngeal carcinoma (NPC) cell line.. NPC cells metastatic to the liver were isolated from nude mice and the invasion and metastatic ability of the cells was observed in vivo and in vitro.. The invasion and metastasis activity of 5-8F-H3B-EGFP (an in vivo isolate with enhanced liver metastatic behaviors) were enhanced obviously in comparison with the parent cell line 5-8F-EGFP. This subline may be useful for cloning genes related to liver metastasis of NPC.

Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Cell Survival; Disease Models, Animal; Female; Green Fluorescent Proteins; Humans; Keratins; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Neoplasm Transplantation

The overall decline in incidence rate of nasopharyngeal carcinoma in Hong Kong during 1988-2002 was limited primarily to a decrease in keratinising carcinoma, which could be explained by the decline in cigarette smoking. Genetic and Epstein-Barr virus interactions may explain the relatively stable incidence rate of non-keratinising carcinoma.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Child; Child, Preschool; Cohort Studies; Female; Hong Kong; Humans; Incidence; Infant; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Registries; Sex Factors

Topics: Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lymphoma, Large B-Cell, Diffuse; Microscopy, Electron; Middle Aged; Mucin-1; Nasopharyngeal Neoplasms

Cyclooxygenase 2 (COX-2), an inducible prostaglandin synthase, participates in inflammatory and neoplastic processes. It is expressed by various tumours and contributes to carcinogenesis. Notably, COX-2 inhibitors appear to have tumour suppressor effects and are being evaluated in clinical trials.. To investigate COX-2 expression in nasopharyngeal carcinoma (NPC), a common tumour in parts of Asia, and to discuss potential implications.. Eighty five cases of NPC were reviewed. COX-2 immunohistochemistry and semiquantitative assessment of expression in nasopharyngeal biopsies were performed. Because COX-2 is proangiogenic, tumour microvessel density was also assessed with the use of CD31 immunohistochemistry.. Histologically, 78 NPCs were undifferentiated, six were non-keratinising, and one was keratinising. Thirty nine NPCs had adjacent dysplastic epithelium. COX-2 expression was noted in 60 NPCs, 14 of 39 samples of dysplastic epithelium, and only one of 25 samples of normal epithelium (p < 0.01). Microvessel density was not significantly different between COX-2 positive and COX-2 negative tumours (p = 0.774). Tumour COX-2 positivity was not associated with higher tumour stage (p = 0.423).. COX-2 expression is more frequently seen as nasopharyngeal epithelium progresses from normal to dysplastic to carcinoma. This suggests that COX-2 contributes to the multistep process of NPC carcinogenesis. COX-2 represents a therapeutic target for COX-2 inhibitors, and there is thus a basis for the further investigation of this adjuvant treatment modality for NPC. COX-2 inhibitors are known to potentiate the antitumour effects of radiotherapy, which is the primary treatment for NPC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Carcinoma, Squamous Cell; Cyclooxygenase 2; Epithelium; Herpesvirus 4, Human; Humans; Immunohistochemistry; Keratins; Membrane Proteins; Microcirculation; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Staging; Peroxidases; Prostaglandin-Endoperoxide Synthases

To study the diagnostic value of cytokeraetin 19 fragment (CYFRA21-1) and tumor supplied group factors (TSGF) in nasopharyngeal carcinoma (NPC).. Serum levels of CYFRA21-1 and TSGF in 82 patients with NPC, 25 patients with benign nasopharyngeal disease and 50 normal controls were measured by electrochemiluminescence immuno-assay.. The levels of CYFRA21-1 and TSGF in NPC group were remarkably higher than those in benign nasopharyngeal disease and normal control groups (P < 0.01). Sensitivities of CYFRA21-1 and TSGF were 48.8% and 57.3%, respectively. The sensitivity of combined detection of two tumor markers increased to 74.3% and the specificity was not decreased significantly.. CYFRA21-1 and TSGF can serve as the serum tumor marker in clinical diagnosis of NPC. Combined detection of two kinds of serum tumor markers increases the detective positive rate.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms

We present the cases of 2 pediatric patients with low-grade nasopharyngeal papillary adenocarcinoma with features suggestive of thyroid origin. Both cases showed strong nuclear immunoreactivity for thyroid transcription factor-1 protein and positive immunostaining for cytokeratins 7 and 19. After thyroid imaging studies, local excision was performed in both patients. The patients remain free of disease 2 and 15 years after treatment, with no evidence of lesions in the thyroid or elsewhere.

Topics: Adenocarcinoma, Papillary; Biomarkers, Tumor; Child; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Nasopharyngeal Neoplasms; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors

Since three-dimensional culture simulates in vivo microenvironment better than planar culture, the biological character of cells in three-dimensional culture model are more similar with that of living tissues. This study was to establish three-dimensional culture models that represent different stages of nasopharyngeal caicinogenesis, and provide information to elucidate the related molecular events.. Non-tumor nasopharyngeal biopsy specimens were used to culture for normal nasopharyngeal epithelial cells. Early and late passages of normal nasopharyngeal epithelial cell line NPNE2 from nasopharyngeal biopsy specimens, immortalized nasopharyngeal epithelial cell line NP69SV40T, nasopharyngeal carcinoma (NPC) cell line SUNE-1 and its high metastatic subclone 5-8F were cultured in Matrigel to establish three-dimensional models.. The cells grew out of non-tumor nasopharyngeal biopsy specimens displayed the morphologic characteristics as epithelia, and could proliferate in vitro for 8-10 passages before senescence. Immunocytochemical staining of cytokeratin revealed that the cells were of epithelial origin. All of the cells, except late passages of NPNE2 cells, could proliferate in the three-dimensional culture system. NPNE2 and NP69SV40T cells mainly developed reticular structures in morphology, and formed few clones with clear and smooth edges as well as tight intercellular junctions. SUNE-1 and 5-8F cells formed clones with irregular morphology, unclear edge, and loose intercellular junctions. In addition, the clones formed by 5-8F cells also developed a lot of pseudopodia, but developed no reticular structure. Late passages of NPNE2 cells formed no clone and reticular structure in the three-dimensional culture.. Normal nasopharyngeal epithelial cells can be successfully cultured in vitro from naspharyngeal biopsy specimens. The three-dimensional culture models, established with normal nasopharyngeal epithelial cells, immortalized nasopharyngeal epithelial cells, and NPC cells, may represent the different stages of nasopharyngeal carcinogenesis.

Topics: Cell Culture Techniques; Cell Line, Tumor; Cells, Cultured; Epithelial Cells; Humans; Keratins; Nasopharyngeal Neoplasms; Nasopharynx

Topics: Aged; Biopsy, Fine-Needle; Bronchiectasis; Carcinoma; Carcinoma, Basal Cell; Diagnosis, Differential; Female; Giant Cells; Granuloma; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Nasopharyngeal Neoplasms; Neoplasms, Multiple Primary; Skin Neoplasms

Cyfra 21-1 is a recognised marker for epidermoid lung and head and neck carcinomas oriented to the cytokeratin 19 that is expressed particularly in malignant epithelial cells. The aims of this study were to evaluate the importance of the use of this marker in nasopharyngeal carcinoma (NPC). Our prospective study interested 41 patients (33M/8F) with a mean age of 44 years (13 to 70) with 8 of them aged less than 30 years, presenting a nasopharyngeal carcinoma histologically confirmed from September 1999 to March 2000 and 45 healthy controls without evidence neoplasm. Undifferentiated forms represent 90.2% of cases and lesions are staged T2, T3 and T4 in 2.4%, 36.6% and 61% of cases, while N1, N2 and N3 represent 9.8%, 26.8% and 41.5% of cases. A blood sample was collected from each patient and control before any treatment, as well as controls to measure Cyfra 21-1 by immunoenzymatic assay, 2 groups of patients were selected after a period varying from 4 to 37 months with a median of 29 months: 27 patients with favourable evolution (without evidence of disease after initial treatment), 12 patients with non favourable evolution (1 death, 2 cases of loco-regional relapse and 9 patients with metastatic disease). 2 patients were lost to follow-up. The results showed that the mean serum Cyfra 21-1 values were significantly higher in patients with NPC than those in controls (p = 0.001). A significant correlation was found between the serum Cyfra 21-1 level before treatment and the clinical outcome of patients (p = 0.0009). Patients having a favourable evolution have the lowest level. Seric level of Cyfra 21-1 at diagnosis of NPC may play a predictive role to evaluate the risk of metastatic disease and prognosis.

Topics: Adolescent; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Case-Control Studies; Female; Humans; Immunoenzyme Techniques; Keratin-19; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Prognosis; Prospective Studies; Sensitivity and Specificity; Tunisia

Patients with undifferentiated nasopharyngeal carcinoma (NPC) have elevated serum levels of CYFRA 21-1 (CYFRA), ferritin, and beta-2-microglobulin (beta2M) compared with healthy control individuals. The prognostic value of these markers has never been validated prospectively.. Paired serum samples from 160 patients with newly diagnosed, nonmetastatic, undifferentiated NPC were collected before radiotherapy (RT) and at 4-6 weeks after the completion of RT. Pre-RT and post-RT levels of serum CYFRA, ferritin, and beta2M were analyzed and correlated with overall survival (OS), progression-free survival (PFS), time to locoregional recurrence, (TLR) and time to distant recurrence (TDR). The results of pre-RT and post-RT plasma Epstein-Barr virus (EBV) DNA levels available from a previous study were included in a Cox regression model together with age, tumor (T) classification, and lymph node (N) classification.. Sixty percent of patients had International Union Against Cancer Stage III-IV disease. At a median follow-up of 116 weeks (range, 37-239 weeks), 38 patients had disease progression. On multivariate analysis, pre-RT CYFRA and post-RT EBV DNA levels were independent predictors of poor OS, post-RT EBV DNA level and N classification predicted poor PFS and TDR; and only T classification predicted TLR. Patients who had pre-RT CYFRA levels > or = 1.5 U/mL were more likely to die (hazard ratio, 1.18; 95% confidence interval, 1.10-1.26) compared with patients who had pre-RT CYFRA levels < 1.5 U/mL. There were no associations between age, post-RT CYFRA levels and pre-RT or post-RT serum ferritin and beta2M levels, and the survival and recurrence rates on multivariate analysis.. Serum CYFRA levels taken before RT predicted reduced survival in patients with nonmetastatic, undifferentiated NPC who underwent RT.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; beta 2-Microglobulin; Biomarkers, Tumor; Carcinoma; DNA, Viral; Female; Ferritins; Herpesvirus 4, Human; Humans; Keratin-19; Keratins; Male; Middle Aged; Multivariate Analysis; Nasopharyngeal Neoplasms; Predictive Value of Tests; Prognosis; Prospective Studies; Survival Analysis

Nasopharyngeal carcinoma (NPC) belongs to the most common malignant tumours in certain parts of the world, e.g. South-East Asia. The undifferentiated type of NPC is associated with genomic Epstein-Barr virus (EBV) DNA. In normal epithelia of the nasopharynx cytokeratins (CK) 4, 5, 6, 13, 14, 15 and 19 are expressed. The aim of this study was to analyse the expression pattern of cytokeratins in NPC in the presence of EBV infection. Twenty primary or metastatic tumours from 13 patients suffering from a NPC were evaluated (formalin-fixed, paraffin-embedded). (35)S-labelled probes were used to detect EBV DNA in the tissue sections. Fourteen specimens (70%) were EBV positive. All positive specimens were undifferentiated NPC. All NPC were identified with broad-spectrum anti-CK antibody. Using a panel of anti-CK antibodies, there was no specific CK-expression pattern in NPC. In summary, undifferentiated NPC are strongly associated with EBV. The cytoskeleton of undifferentiated NPC reveals no specific pattern of CK expression.

Topics: Adult; Aged; DNA Probes; DNA, Viral; Female; Herpesvirus 4, Human; Humans; In Situ Hybridization; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms

Nasopharyngeal carcinoma (NPC) has a high potential to develop distant metastasis after radiotherapy. Cytokeratin 19 (CK-19) mRNA has been frequently used as a marker in the detection of circulating tumor cells of epithelial origin, but has rarely been investigated in NPC. This study was performed to evaluate the effect of blood sampling and different Taq DNA polymerase on the results of nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay.. Peripheral blood samples from a total of 37 NPC patients with well-documented distant metastasis (M1) were collected before treatment. Eighteen patients had more than one blood sampling. Five different Taq DNA polymerases were used to test the blood from 17 patients. Peripheral blood of 37 nonmetastatic (M0) NPC patients was tested by the same nested RT-PCR system using multiple Taq DNA polymerases to evaluate the impact of multienzyme assay in the prediction of subsequent distant metastasis.. Among M1 NPC patients, the accumulative positive rates of CK-19 mRNA were 22.2%, 44.4%, 70.6%, 75.0%, and 80.0% when one, two, three, four, or five blood sampling were taken, respectively. The accumulative positive rates increased as the numbers of different enzymes increased-from 35.5% by one enzyme to 82.4% by five enzymes. Six of 37 M0 patients had distant metastasis develop after a median follow-up time of 20 months. The detection sensitivity for four-enzyme test (5 of 6 = 83.3%) is better than that of one-enzyme test (2 of 6 = 33.3%).. Our data demonstrate that multiple blood sampling or using multiple enzymes for nested RT-PCR assay significantly enhances the sensitivity in the molecular diagnosis of NPC metastasis.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; DNA-Directed DNA Polymerase; Female; Humans; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplastic Cells, Circulating; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Taq Polymerase

Sinonasal undifferentiated carcinoma (SNUC) is a highly aggressive malignant neoplasm that is often difficult to distinguish from other poorly differentiated carcinomas arising in the sinonasal tract. To search for a differential cytokeratin (CK) expression that could be useful for diagnostic purposes, we compared the expression of a large panel of CKs in a series of 6 SNUCs, 10 poorly differentiated squamous cell carcinomas (SCCs), 10 nonkeratinizing squamous cell carcinomas (NKSCCs), and 5 nasopharyngeal-type undifferentiated carcinomas (NPTCs). SCC, NKSCC, and NPTC frequently showed immunoreactivity for CK5/CK6, CK8, CK13, and CK19. In addition, SCC and NKSCC expressed CK14, which was not detected in NPTC, and SCC expressed CK7 (60% of cases) and CK4 (30% of cases), which were absent in NKSCC and NPTC. Three NKSCCs were associated with a Schneiderian papilloma, and the results of the immunostaining were similar in the two components, with the exception of CK4 and CK7, which were expressed by the papilloma and not by the carcinoma. In contrast to other carcinomas, SNUC was characterized by the exclusive expression of CKs of simple epithelia, such as CK8 (100% of cases), CK7 (50% of cases), and CK19 (50% of cases). Thus, there are significant differences in the pattern of CK expression between SNUC, SCC, NKSCC, and NPTC, which could be of diagnostic aid. Moreover, these findings support the hypothesis that SNUC is a separate entity from SCC and NPTC of the sinonasal tract.

Topics: Adult; Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Nose Neoplasms; Paranasal Sinus Neoplasms

The reverse transcriptase-polymerase chain reaction (RT-PCR) technique is a tool capable of detecting minute quantities of circulating tumor cell-derived transcripts. Nasopharyngeal carcinoma (NPC) is a rapidly growing tumor of epithelial origin and high metastatic potential. The aim of our study is to investigate the clinical value of circulating cytokeratin-19 (CK-19) mRNA detection in NPC patients. Between June 1997 and March 1999, 57 previously untreated, advanced NPC patients without distant metastasis were uniformly treated by concurrent chemoradiotherapy. Peripheral blood samples were collected prospectively before treatment and subjected to a nested RT-PCR assay. Measures were taken to prevent contamination and pseudogene interference. PCR products of positive results were verified by restriction enzyme Hae II and direct sequencing. Under our nested RT-PCR experimental conditions, 33.3% (19/57) clinically nonmetastatic NPC patients had CK-19 mRNA in their blood. The positive detection rates of CK-19 mRNA in the peripheral blood for different stages were 20.0% for stage II, 31.6% stage III and 43.5% stage IV (p = 0.1335). After a median follow-up time of 35 months, 2 patients had recurrences of their primary tumors and 14 developed distant metastases without locoregional recurrence. Nine of 19 (47.4%) CK-19 mRNA-positive patients and 5 of 38 (13.2%) CK-19 mRNA-negative patients developed distant metastasis (p = 0.00826). The 3-year metastasis-free survival rates were 49.9% for patients with detectable CK-19 and 85.9% for those with undetectable CK-19 (p = 0.0089, log-rank test). Our data suggest that the presence of CK-19 mRNA in the peripheral blood may be a potential marker of micrometastasis for NPC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma; Cisplatin; False Positive Reactions; Female; Fluorouracil; Follow-Up Studies; Humans; Keratins; Life Tables; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Neoplasm Proteins; Polymorphism, Restriction Fragment Length; Predictive Value of Tests; Prognosis; Prospective Studies; Pseudogenes; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Survival Analysis; Survival Rate; Treatment Outcome

Nasopharyngeal carcinoma (NPC) harbors a higher metastatic potential than other head and neck cancers. In order to seek a possible surrogate marker for early detection of recurrent or metastatic disease, we tested the feasibility of cytokeratin-19 (CK-19)-nested reverse-transcription polymerase chain reaction (RT-PCR) for detecting circulating tumor cells in NPC patients.. Two tubes of blood were sequentially collected in individual draws from 7 NPC patients and 15 healthy persons. Total ribonucleic acid (RNA) was extracted from blood cells and treated with deoxyribonuclease. The RNA was then subjected to RT and nested PCR with specific CK-19 primers. The reaction products were run on an agarose gel and visualized under UV light. The sequences of the products were determined using an ABI377 automatic sequencer.. Among the 7 NPC cases, 4 cases presented CK- 19 expression with 2 in both tubes, 1 in the first tube, and 1 in the second tube. In the control group, 8 of 15 cases also presented CK-19 expression with 6 in both tubes and 2 in the second tube resulting in a 53.3% false-positive rate. Incidentally, an aberrant splicing product lacking exon 4 of CK-19 messenger RNA was discovered.. Results of the present study indicate that the CK-19-nested RT-PCR is not suitable for detecting circulating tumor cells in NPC patients because of a high false-positive rate in the control group. The reason for the high rate of false-positives may be attributed to pseudogenes, different blood cell separation methods, or illegitimate expression of CK-19 in blood cells.

Topics: False Positive Reactions; Humans; Keratins; Nasopharyngeal Neoplasms; Neoplastic Cells, Circulating; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Gangliocytic paraganglioma (GP) is a rare neoplasm described almost exclusively in the gastrointestinal tract, especially the periampullary region. However, several examples have been reported at various sites, including the stomach, jejunum, and appendix. Herein we report a case of GP involving the nasopharynx. To our knowledge, this is the first report of GP at this site. A 44-year-old woman presented with headaches and symptoms of fullness and pressure related to mass effect. An initial endoscopic biopsy was followed by surgical excision of the nasopharyngeal mass. The triphasic tumor fulfilled the morphologic and immunohistochemical criteria for GP. The histogenesis of GP is uncertain, and the current belief is that it arises from the embryonic ventral pancreas. This concept is based largely on the location of most cases, which is along the embryologic migration route of the ventral pancreas, as well as the expression of pancreatic polypeptide by the tumor. The nasopharyngeal location of our case clearly refutes the pancreatic origin of GP. We propose that the tumor probably arises from totipotential adult stem cells, which in the right microenvironment differentiate along nonnative cell lineages.

Topics: Adult; Biopsy; Chromogranins; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Nasopharyngeal Neoplasms; Paraganglioma; S100 Proteins; Synaptophysin; Tissue Embedding; Vasoactive Intestinal Peptide

CYFRA 21-1 is a newly developed tumor marker that is especially useful for detecting squamous cell carcinoma (SCC) of the lung. Squamous cell carcinoma antigen is a proven tumor marker that is especially useful for detecting SCC of the cervix. Our aim in this study was to compare the clinical value of CYFRA 21-1 and SCC antigen in the detection of nasopharyngeal carcinoma (NPC). Serum levels of CYFRA 21-1 and SCC antigen were measured in 80 untreated NPC patients and 77 healthy controls. The cutoff values of CYFRA 21-1 and SCC antigen, determined at the 95th percentile of the 77 healthy controls, were 2.48 ng/mL and 1.49 ng/mL, respectively. The results revealed that the mean serum value of only CYFRA 21-1 was significantly higher in the 80 NPC patients than in the 77 healthy controls, and the detection sensitivity of CYFRA 21-1 for NPC was significantly higher than that of SCC antigen. In conclusion, our results suggest that CYFRA 21-1 is a better tumor marker than SCC antigen for detection of NPC.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Sensitivity and Specificity; Serpins

The Epstein-Barr virus (EBV) is associated with two major human epithelial malignancies, where it is likely to play a role in the malignant phenotype: undifferentiated nasopharyngeal carcinoma (100% of cases) and gastric carcinomas (about 10% of cases). We and others have obtained growth transformation of monkey kidney primary epithelial cells by transfection of viral DNA, especially with the BARF1 gene of EBV (Wei et al., 1997). We now report that the same type of primary epithelial cells can be growth-transformed using EBV particles derived from a nasopharyngeal carcinoma tumor line. Not only can these EBV-infected cells grow over 100 passages, escaping senescence, in contrast to their noninfected counterparts, but they can also survive and proliferate at very low cell density. Several subclones were characterized in terms of viral gene expression. All these clones gave a similar pattern, with detection of EBNA1 and BARF1 proteins but absence of LMP1. CD21, which is the main EBV receptor on B lymphocytes, was not expressed on parental monkey kidney epithelial cells nor on EBV-infected cell clones. This model of epithelial cell transformation will be useful for a better investigation of EBV functions critical for oncogenesis of epithelial cells.

Topics: Animals; Carcinogenicity Tests; Cell Division; Cell Transformation, Viral; Cells, Cultured; Epithelial Cells; Epstein-Barr Virus Nuclear Antigens; Gene Expression; Genes, Viral; Genome, Viral; Haplorhini; HeLa Cells; Herpesvirus 4, Human; Humans; Keratins; Mice; Mice, Nude; Nasopharyngeal Neoplasms; Receptors, Complement 3d; Tumor Cells, Cultured; Viral Matrix Proteins; Viral Proteins

Nasopharyngeal carcinoma (NPC) is a radiosensitive tumor. Because of recent advances in radiation oncology, distant metastasis has become the predominant failure site after adequate radiotherapy. The purpose of this study is to establish a nested reverse transcriptase-polymerase chain reaction (RT-PCR) system and to evaluate the potential of cytokeratin 19 (CK-19) mRNA as a target for detecting micrometastasis in the blood of NPC patients. Venous blood samples from 40 patients with biopsy-proven NPC (25 previously untreated and 15 after radiotherapy) and 20 healthy volunteers were tested. We divided the 40 patients into 4 groups: cured, early stage, advanced stage, and metastasized, according to results of clinical staging work-up. Under our nested RT-PCR experimental conditions, 2 of 8 early stage patients (25.0%), 6 of 15 advanced stage patients (40%), and 6 of 8 patients with distant metastasis (75%) had CK-19 positive cells in peripheral blood (P = 0.11). No CK-19 positive cells were detected in 9 "cured" patients and 20 healthy volunteers. Our data indicated that the positive detection rate for CK-19 mRNA in peripheral blood increased as the clinical stage of disease increased, but the difference did not reach statistical significance. Longer follow-up is needed to assess the significance of CK-19 mRNA in blood, as well as its relation to subsequent metastasis and prognosis of NPC.

Topics: Adult; Aged; Female; Humans; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplastic Cells, Circulating; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

To investigate the possible pathogenetic role of cytokeratin 13 (CK13) gene expression in human nasopharyngeal carcinoma (NPC).. Tissue samples taken from a total of 40 cases of NPC and 8 cases of chronic inflammation of nasopharyngeal epithelium (CINE) were immunohistochemically studied for CK13 protein expression. Northern blot hybridization was used to detect CK13 gene at mRNA level in 32 of the 40 NPC and in 8 CINE cases. Correlations of CK13 expression with the clinical features of NPC were also investigated.. Significantly stronger immunoreactivity for CK13 protein was shown in CINE than in NPC tissues (P < 0.01), so did it at mRNA levels. Significantly higher CK13 expression was demonstrated in patients with cervical lymph node metastasis, as compared to those without (P < 0.05). However, no significant correlation between CK13 expression and clinical staging of the disease.. The decreased expression of CK13 in NPC suggests that differentiation disturbance of the nasopharyngeal epithelium might play a role in the pathogenesis of NPC.

Topics: Adolescent; Adult; Aged; Blotting, Northern; Female; Gene Expression; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms

To study the significance of cytokeratin 13 (CK13) gene expression and its methylation in human nasopharyngeal carcinoma (NPC).. The expression of CK13 in 32 cases of NPC and 8 cases of chronic inflammatory diseases of nasopharyngeal epithelia (CIDNE) was studied using Northern blot hybridization. The methylation pattern of CK13 gene was analyzed by Southern blot hybridization using methylation sensitive restriction endonuclease Hpa II and Msp I in NPC cell lines HNE1 and normal human primary cultures of nasopharyngeal epithelial cells.. High expression of CK13 gene was found in 8(100%) CIDNE, low-expression of the gene in 12(37.5%) NPC, negative expression in 9(28.1%) and high expression in 11(34.4%). The degree of methylation was increased in NPC cell lines HNE1, compared to that of normal human primary cultures of nasopharyngeal epithelial cells.. The expression of the CK13 gene in NPC is partly or completely down regulated. It is possibly related to hyper-methylation of CK13 gene.

Topics: Gene Expression Regulation, Neoplastic; Humans; Keratins; Molecular Weight; Nasopharyngeal Neoplasms

Six hundred and ninety-three Chinese patients with non-metastatic nasopharyngeal carcinoma (NPC) were treated at one institution under a uniform protocol between 1984 and 1989. The tumour histology of these patients was subjected to a standardized review and classified into two distinct groups of World Health Organization (WHO) type I (keratinizing squamous cell carcinoma) (n = 13) or WHO types II and III (non-keratinizing carcinoma and undifferentiated carcinoma) (n = 662). The differentiation between the two groups was uncertain in 18 patients. The patient characteristics and clinical outcome after a uniform treatment policy of the two groups were not statistically significantly different. The low incidence of WHO type I NPC may account for the lack of prognostic significance of this histological subtype in Chinese populations.

Topics: Actuarial Analysis; Biopsy; Carcinoma; Carcinoma in Situ; Carcinoma, Squamous Cell; Confidence Intervals; Disease-Free Survival; Female; Humans; Incidence; Iridium Radioisotopes; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Odds Ratio; Prognosis; Proportional Hazards Models; Radiopharmaceuticals; Radiotherapy Dosage; Survival Rate; Treatment Outcome; World Health Organization

Simultaneous detection of two antigens by immunostaining usually requires primary antibodies from two different species or a hapten modification of one of the antibodies if they are from the same species. A novel double staining method is described for immunodetection of two independent antigens using two mouse monoclonal antibodies. The principle of the method is the following: The first antigen is detected by a monoclonal antibody that is diluted so extensively that it cannot be recognized with conventional detection systems. A highly sensitive biotin-tyramide amplification system is used to identify this antibody. The second antigen is stained with a monoclonal antibody by dilution and detected by conventional immunostaining. The method was tested for both alkaline-phosphatase staining on paraffin sections and immunofluorescence staining on cultured cells in cytospin preparation. The absence of cross-reaction in the former system was demonstrated by the mutually exclusive detection of T- and B-cells in human lymph nodes or T-cells and carcinoma cells in nasopharyngeal carcinoma biopsies. Similarly, the EBV encoded EBNA2 and ZEBRA proteins showed a mutually exclusive staining by immunofluorescence on B95-8 cells. The method could be used to demonstrate co-expression of two independent antigens in the same cells, such as PCNA and keratin in carcinoma cells in paraffin sections and for EBNA2 and LMP1 EBV proteins in immunofluorescence preparations of B95-8 cells.

Topics: Alkaline Phosphatase; Animals; Antibodies, Monoclonal; Antigens; Antigens, CD; Antigens, Viral; Biotin; Cross Reactions; Fluorescent Antibody Technique; Herpesvirus 4, Human; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Lymphoid Tissue; Mice; Nasopharyngeal Neoplasms; Paraffin Embedding; Proliferating Cell Nuclear Antigen; Tumor Cells, Cultured; Tyramine

Over a 32-month period at the University Hospital, Kuala Lumpur, we were able to study the cytological appearance of metastatic nasopharyngeal carcinoma (NPC) in 17 cases. This comprised 14 males and three females of which 13 were Chinese, three were Malay, and one was Indian. Their ages ranged from 27 to 64 years. Histological correlation was available in all the patients in the form of nasopharyngeal biopsies, and they were classified as per the World Health Organization classification into types I, II, and III NPC. Smears from type II NPC showed good cellularity with mainly clustered and occasionally dissociated cells, with focal columnar appearance, vesicular nuclei, prominent nucleoli, and variable amounts of cytoplasm. Clusters of malignant cell closely associated with lymphoid cells and dissociation of malignant cells were more characteristic of type III NPC. FNA cytology is now applied extensively to the diagnosis of head and neck tumours and knowledge of the cytomorphology of NPC would greatly aid in pinpointing the primary of this tumour which is notorious for presenting with early nodal metastasis.

Topics: Adult; Biopsy, Needle; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local

The cytologic features in fine-needle aspirates from a rare benign nasopharyngeal salivary gland anlage tumor in a newborn boy are described and commented on, regarding therapeutically important differential diagnoses.

Topics: Biomarkers; Biopsy, Needle; Humans; Immunohistochemistry; Infant, Newborn; Keratins; Male; Nasopharyngeal Neoplasms; Salivary Gland Neoplasms

Nasopharyngeal carcinoma is a subset of head and neck squamous cell cancers with unique endemic distribution and aetiological co-factors. Epstein-Barr virus has been revealed to be an important aetiological factor for most nasopharyngeal carcinomas. Nevertheless, additional genetic alterations may be involved in their development and progression. The aim of this study was to determine the likely chromosomal locations of tumour-suppressor genes related to Epstein-Barr virus-associated nasopharyngeal carcinoma. Fifty-six microsatellite polymorphic markers located on every autosomal arm were used to estimate the incidence of loss of heterozygosity in 27 Epstein-Barr virus-associated nasopharyngeal carcinomas. High frequencies of allelic loss were observed on chromosome 3p (75.0%) and 9p (87.0%). Chromosome 9q, 11q, 13q and 14q displayed loss in over 50%, while chromosome 3q, 6p, 16q, 19q and 22q exhibited loss in 35-50%. Furthermore, several other chromosomal arms demonstrated allelic loss in 20-35%. Additionally, 1 of the 27 cases showed microsatellite instability at multiple loci. These findings provide evidence of multiple genetic alterations during cancer development and clues for further studies of tumour-suppressor genes in Epstein-Barr virus-associated nasopharyngeal carcinoma.

Topics: Carcinoma; Cell Adhesion Molecules; Chromosome Mapping; DCC Receptor; DNA, Neoplasm; DNA, Viral; Herpesviridae Infections; Herpesvirus 4, Human; Heterozygote; Humans; Keratins; Microsatellite Repeats; Nasopharyngeal Neoplasms; Receptors, Cell Surface; Sequence Deletion; Tumor Suppressor Proteins; Tumor Virus Infections

The histopathological findings of two cases of primary lymphoepithelioma-like carcinoma (LELC) of the skin occurring in two elderly Chinese individuals are presented. Microscopically, they were well circumscribed and were composed of irregular nests of malignant epithelial cells in a background of reactive lymphoid cells including mature plasma cells. A focus of epithelial dysplasia was noted in the adjacent epidermis in one case, suggesting that the LELC might have originated from the overlying epidermis. The epithelial nature of the tumors was confirmed by cytokeratin staining. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) showed that the tumor cells were uniformly negative, although positive signals were detected in scattered background lymphocytes in case 1. Our results confirm the previous observation that LELC of skin is not related to Epstein-Barr virus, even in Chinese subjects. Nevertheless, such negative findings may prove to be of diagnostic value in excluding the alternative more common diagnosis of metastatic nasopharyngeal carcinoma, which is uniformly positive for EBER.

Topics: Aged; Aged, 80 and over; Carcinoma; Carcinoma, Squamous Cell; China; Epidermis; Epithelium; Female; Herpesvirus 4, Human; Humans; In Situ Hybridization; Keratins; Lymphocytes; Lymphoid Tissue; Male; Nasopharyngeal Neoplasms; Plasma Cells; RNA, Viral; Skin Neoplasms

CYFRA 21-1 is a fragment of cytokeratin expressed by simple epithelia and their malignant counter-parts. Serum CYFRA 21-1 levels were studied in 240 new cases of nasopharyngeal carcinoma and 19 patients who developed distant metastases. A reference range of < 2 U/ml for our local Chinese population was established in 55 sex- and age-matched healthy volunteers. The nasopharyngeal carcinoma patients had significantly higher marker levels than the healthy controls and the mean level increased with advancing stage. However, the low percentage of elevation in early stages means that the marker is not useful for screening. The overall percentage (52.5) of elevation in 240 newly diagnosed squamous cell carcinoma of the nasopharynx is comparable to that of squamous cell carcinoma of the lungs, suggesting that the expression of CYFRA 21-1 is related to the cell type rather than the tissue type of the carcinoma, 46 (95.8%) of 48 patients with metastatic nasopharyngeal carcinoma showed an elevated value of CYFRA 21-1. This extremely high percentage implies that it is very unlikely for a patient with a normal value to have distant metastasis. This may permit major economies in radiological screening for distant metastasis. Preliminary results from serial measurement of the marker indicated its potential for monitoring response to treatment and for early detection of distant metastasis.

Topics: Biomarkers, Tumor; Follow-Up Studies; Humans; Keratins; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Neoplasm Staging; Prognosis

Epidemiological studies have implied that Chinese salted fish is a human nasopharyngeal carcinogen. In the present study, 162 Sprague-Dawley rats were randomly assigned to one of four experimental groups. Rats in groups 1 (n = 41) and 3 (n = 40) were exposed to salted fish from birth through the breast feeding period by giving the maternal rats a diet containing 10% and 5% salted fish, respectively, later feeding the rats with pellets containing 10% and 5% of salted fish respectively. In group 2, the rats (n = 41) were given pellets containing 10% of salted fish from 6 weeks of age. Rats in group 4 (n = 40), serving as controls, were only given ordinary pellets. Three rats had nasopharyngeal tumours, 2 from group 1 had a poorly differentiated carcinoma and a squamous cell carcinoma. One rat from group 2 had a squamous cell carcinoma. Four rats had nasal tumours, one fibrosarcoma and one adenocarcinoma were found in rats from group 1. One rhabdomyosarcoma was found in group 2, and one soft tissue sarcoma was found in a rat in group 3. No nasal or nasopharyngeal tumours appeared in the control group. The difference in the occurrence of malignant nasal and nasopharyngeal tumours among the four experimental groups was statistically significant (one tailed p for trend = 0.041). The frequency of tumours appearing in other organs such as the breast, kidney, lung, liver and brain was not significantly different between the salted fish treated groups and the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Animals; Animals, Newborn; Body Weight; Carcinoma; Carcinoma, Squamous Cell; Desmin; Diet; Female; Fibrosarcoma; Fishes; Food Preservation; Keratins; Male; Nasopharyngeal Neoplasms; Nose Neoplasms; Pregnancy; Rats; Rats, Sprague-Dawley; Rhabdomyosarcoma; Sarcoma, Experimental; Survival Rate; Vimentin

Inhibition studies were carried out to study possible cross-reactivity between a peptide fragment of the Epstein-Barr virus nuclear antigen, EBNA-1, and keratin/collagen. The 20-amino acid peptide (pAG), derived from a glycine-alanine repeat region of EBNA-1, uniquely makes up about one-third of the viral protein and is a dominant IgA antigenic epitope in patients with nasopharyngeal carcinoma (NPC). A small percentage of normal human sera (NHS) also binds pAG and this reactivity is examined in this study. Ten percent (2/20) and 13.4% (2/15) of IgA-pAG-positive NPC sera and NHS, respectively, were significantly inhibited by keratin in a competitive ELISA system. Conversely, 31.6% (6/19) and 30.8% (4/13) of IgA-keratin-positive NPC sera and NHS, respectively, were significantly inhibited by pAG. This indicated minimum cross-reactivity between IgA serum antibodies to EBNA-1 and keratin. Using collagen as inhibitor, none of 18 and only 2/13 IgA-pAG-positive NPC sera and NHS, respectively, were inhibited. In the collagen ELISA system, only 2/19 (10.5%) and 4/25 (16%) of IgA-collagen-positive NPC sera and NHS, respectively, were inhibited with pAG. Therefore, cross-reactivity with collagen was also low. IgA-pAG-positive NHS may therefore not be a false positive phenomenon, but whether it may represent an early serological profile related to NPC carcinogenesis remains to be determined.

Topics: Alanine; Amino Acid Sequence; Antigens, Viral; Binding, Competitive; Collagen; Cross Reactions; DNA-Binding Proteins; Enzyme-Linked Immunosorbent Assay; Epstein-Barr Virus Nuclear Antigens; Glycine; Herpesvirus 4, Human; Humans; Immunoglobulin A; Keratins; Molecular Sequence Data; Nasopharyngeal Neoplasms; Repetitive Sequences, Nucleic Acid

Immunohistochemical analysis was carried out to examine the characteristics of nasopharyngeal carcinoma (NPC) using 38 biopsy cases obtained from southern China. These cases were divided into 3 groups according to their predominant pattern associated with cell and tissue differentiation which is based on World Health Organization (WHO) classification as follows: 6 cases of squamous cell carcinoma (16%), 25 cases of differentiated non-keratinizing carcinoma (66%), 7 cases of undifferentiated carcinoma (18%). All tumor tissues reacted with MB-1, but they did not react with L26 (CD20), 4KB5 (CD45R), MT-1, and leukocyte common antigen (LCA). Keratin and epithelial membrane antigen (EMA) as epithelial markers focally stained NPC tissues in all cases. Carcinoembryonic antigen (CEA)-positive staining was detected in 7 (28%) of the 25 cases of differentiated non-keratinizing carcinoma and in 3 (43%) of the 7 cases of undifferentiated carcinoma; thus, of 38 cases, 10 (26%) were CEA-positive. On the other hand, squamous cell carcinoma cases did not react with CEA. These NPC tissues did not react with S-100 protein, alpha-1-antichymotrypsin (ACT), lysozyme, vimentin, and desmin. Therefore, it is concluded that some cases of NPC are difficult to distinguish from malignant lymphoma. In certain cases, NPC may be distinguished from malignant lymphoma, using immunohistochemical methods for the detection of MB-1, keratin, EMA, and LCA. Specifically, this evidence suggests that MB-1 may be useful as a tumor marker of NPC. Moreover, the CEA reaction to NPC may be related to the cell differentiation.

Topics: Antigens, CD; Antigens, CD20; Antigens, Differentiation, B-Lymphocyte; Antigens, Neoplasm; B-Lymphocytes; Biopsy; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Membrane Glycoproteins; Mucin-1; Nasopharyngeal Neoplasms

By employing cytochemistry, immunocytochemistry, selective double extraction, whole mount electron microscopy and electrophoretic scanning quantitative analysis, the intermediate filaments (IF) of in vitro cultured nasopharyngeal carcinoma cell lines CNE-1 (highly differentiated) and CNE-2Z (poorly differentiated) have been studied. The results demonstrated that although the keratin-type IF were organized in a network pattern in both kinds of cells, significant differences could be observed between the two kinds of cells regarding IF organization, subtypes and quantity of keratin. The poorly differentiated cell line CNE-2Z exhibited a far more irregular and confused IF organization structure, and the content of keratin was lower while the variety of keratin subtypes was increased.

Topics: Carcinoma; Humans; Intermediate Filaments; Keratins; Nasopharyngeal Neoplasms; Tumor Cells, Cultured

Upon 2-3 hours cold treatment (0 degrees C), the keratin filaments of some PcaSE-1 cells and BEL-7404 cells are partly transformed into granular aggregates. But such structural transformation does not occur in HeLa cells and CNE cells. By rewarming (37 degrees C) cells within 15-30 minutes, this structural changes of keratin filaments in PcaSE-1 cells and BEL-7404 cells are readily reversed. In contrast, in HeLa cells and CNE cells, keratin filaments are transformed into granula aggregates during mitosis, but the keratin filament network in PcaSE-1 cells and BEL-7404 cells remained intact and encircled the developing mitotic spindle as the cells entered mitosis. Results suggest that the above two types of keratin filament structural transformation might be induced by different factors. Our results also indicate that: (1) PcaSE-1 cells treated with colchicine alone or with combination of colchicine and cytochalasin D does not cause granular aggregates of keratin filaments. However, after depolymerization of microtubules with colchicine, the response of the cells to cold treatment is intensified. (2) The aggregate formation during cold treatment is unrelated to whether epithelial cells contain two different type intermediate filaments or not. (3) Epithelial cells preextracted with Triton X-100 do not induce granular aggregate formation of keratin filaments upon cold treatment. (4) The structural transformation upon cold treatment may be a characteristic of keratin filaments of certain epithelial cell lines.

Topics: Cold Temperature; Cytoplasmic Granules; Epithelium; HeLa Cells; Humans; Intermediate Filaments; Keratins; Liver Neoplasms; Nasopharyngeal Neoplasms; Skin Neoplasms; Tumor Cells, Cultured

A pulsed Holmium:YAG-laser (lambda = 2,120 nm) was used for the first time clinically in tumour surgery. The primary lesion of a transitional cell carcinoma of the nasopharynx with metastatic disease in the neck (T2N2Mo) was laser resected in a photoablative manner with a minor thermal component without danger of damage to the skull base. Neck dissection was performed by conventional surgery. In comparison to laser types depending primarily on the thermal effects of laser-tissue interaction the coagulative necrosis zone following Holmium:YAG-laser surgery is small and there is no area of carbonisation. Macroscopic wound healing showed no complications and was completed after three weeks. At this time radiation therapy was started. The results of the histological examination and the physical properties of this new infrared laser system are discussed as well as the possibilities of flexible fiber Holmium:YAG endoscopic laser tumour surgery in clinical use.

Topics: Carcinoma, Transitional Cell; Endoscopy; Humans; Keratins; Laser Therapy; Lymph Nodes; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Middle Aged; Nasopharyngeal Neoplasms; Nasopharynx; Neck Dissection

Nasopharyngeal carcinoma (NPC) has a relatively high incidence in Chinese living in Taiwan, Hong Kong, Singapore, and South China. To better understand this cancer, we have established several new NPC cell lines.. We collected biopsy specimens from suspected NPC patients and divided each specimen into two parts: the first part was fixed for routine histopathologic examination, and the other part was put into culture medium for primary culture. Once the cell lines were established, they were extensively characterized.. Seven NPC cell lines were established, and all have been passaged more than 100 times. Two lines were derived from keratinizing carcinomas and five from undifferentiated carcinomas. Electron microscopic examination revealed that both dark and light tumor cells contained intermediate filaments with clear desmosome formation. The average doubling time ranged from 10.7 to 16.3 hours. Karyotypic analysis showed multiple chromosome abnormalities with the average chromosome number between 84 and 95. Colony forming efficiency in soft agar was 18-42%. All cell lines could induce solid tumor mass formation when transplanted into nude mice, and the histopathological findings showed two keratinizing and five nonkeratinizing carcinomas. All cell lines contained less acidic keratin polypeptides than basic keratin polypeptides. Strong expression of vimentin in each single cell of all cell lines was also observed. The oncosuppressor retinoblastoma gene in each cell line showed no remarkable abnormality, but retinoblastoma protein was abnormally expressed in some interphase cells. The oncogenes, erbB and c-fgr, were both normally expressed. While the c-myc oncogene in all cell lines was overexpressed when compared with the Burkitt's lymphoma Raji Cell line, the c-myc DNA sequence in each cell line showed neither amplification nor rearrangement.. The newly established seven NPC cell lines have been well characterized, and all showed overexpression of c-myc oncogene. The oncosuppressor retinoblastoma gene revealed no remarkable rearrangement, but its protein product was abnormal in certain interphase cells of each cell line.

Topics: Adult; Aged; Antigens, Viral; Carcinoma; DNA-Binding Proteins; Epstein-Barr Virus Nuclear Antigens; Female; Genes, Retinoblastoma; Humans; Karyotyping; Keratins; Male; Microscopy, Electron; Middle Aged; Nasopharyngeal Neoplasms; Proto-Oncogene Proteins c-myc; Tumor Cells, Cultured; Tumor Stem Cell Assay; Vimentin

We describe two patients with nasopharyngeal carcinoma who initially presented with cervical lymphadenopathy. Lymph node biopsy specimens in each patient were initially diagnosed as Hodgkin's disease. In both cases, the neoplastic cells had large, vesicular nuclei with prominent eosinophilic nucleoli; some neoplastic cells were identified in lacunar spaces. In addition, numerous inflammatory cells were present, including eosinophils, lymphocytes, and plasma cells. At the time of referral, the correct diagnosis of metastatic carcinoma was made, and primary nasopharyngeal carcinomas were subsequently identified. The possibility of metastatic nasopharyngeal carcinoma should always be considered in adults with enlarged cervical lymph nodes that resemble Hodgkin's disease. The cytologic features of the malignant cells are the clue to the correct diagnosis. Immunophenotypic studies easily resolve this diagnostic dilemma if the possibility of metastatic nasopharyngeal carcinoma is considered.

Topics: Adult; Aged; Biopsy; Diagnosis, Differential; Eosinophils; Female; Hodgkin Disease; Humans; Immunophenotyping; Keratins; Lymph Nodes; Lymphatic Diseases; Lymphatic Metastasis; Lymphocytes; Male; Nasopharyngeal Neoplasms; Uterine Cervical Diseases

Nasopharyngeal carcinoma (NPC) can provoke a local granulomatous reaction which may cause diagnostic difficulty. To further elucidate this possible diagnostic pitfall, 47 cases who were initially diagnosed as tuberculosis or granulomatous inflammation were reexamined; 7 cases (15%) were found to have NPC. In a routine histological stain, residual malignant tumor cells could be identified in 2 cases. In the remaining 5 cases, malignant tumor cells could only be accurately identified after careful examination. Immunohistochemical staining for keratin easily demonstrated the residual tumor cells engulfed in a granulomatous lesion in all 7 cases. This finding suggests that an immunohistochemical stain for keratin is useful and should be performed for any nasopharyngeal biopsy showing granulomatous lesion with suspicion of malignancy, particularly in countries where NPC is prevalent. The overall 5-year survival rate among these NPC patients was 83%, a most favorable outcome, which suggests that a granulomatous reaction may reflect a favorable local host, and a cell-mediated immune response.

Topics: Adult; Carcinoma; Female; Follow-Up Studies; Granuloma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Prognosis

By indirect immunofluorescence microscopy and electron microscopy, we studied the behavior of intermediate filaments during mitosis in three human epithelial cell lines, derived from normal epidermis (PcaSE-1, from a cancer patient), stratified epithelium (CNE, from nasopharyngeal carcinoma) and simple epithelium (SPC-A-1 from lung adenocarcinoma) respectively. CNE cells and SPC-A-1 cells express two different intermediate filament systems; keratin filaments and vimentin filaments, but PcaSE-1 cells only express keratin filaments. The keratin filament system in PcaSE-1 cells remained intact and encircled the developing mitotic spindle as the cells entered mitosis. In contrast, in CNE cells and SPC-A-1 cells, keratin filaments appeared to disassemble into amorphous cytoplasmic bodies during mitosis. However, their vimentin filaments remained morphologically intact throughout mitosis. We propose; (1) The disassembly of keratin filaments in mitotic epithelial cells is more or less associated with the degree of their cell malignancy rather than with the abundance of keratin filaments in interphase. (2) Intermediate filaments may be involved in the positioning and/or centering of the spindle during mitosis. (3) The possible function of vimentin filament system in CNE cells is positioning and orientation of chromosomes.

Topics: Adenocarcinoma; Cell Line; Epithelial Cells; Epithelium; Humans; Intermediate Filaments; Keratins; Lung Neoplasms; Mitosis; Nasopharyngeal Neoplasms; Tumor Cells, Cultured; Vimentin

The association of Epstein-Barr virus (EBV) with nasopharyngeal carcinoma (NPC) has been known for some time, but the precise role of EBV in this cancer is poorly understood, due partly to the lack of an in vitro system for studying NPC cells and the effect of EBV on epithelial cells. Biopsies of NPC tumours have revealed expression of the EBV latent membrane protein (LMP) in 65% of cases, suggesting that in at least some NPC tumours LMP may contribute to cell transformation. Here we address the question of the effect of LMP expression on epithelial cells. Transfection of an immortalized, non-tumorigenic keratinocyte cell line (RHEK-1) with the LMP gene causes a striking morphological transformation: the originally flat, polygonal colonies change to bundles of spindle-shaped cells that form multilayer foci, and cytokeratin expression is down-regulated. Our results suggest that LMP expression may be an important causal factor in the development of NPC.

Topics: Antigens, Viral; Blotting, Western; Cell Transformation, Viral; Cells, Cultured; Genes, Viral; Herpesvirus 4, Human; Humans; In Vitro Techniques; Keratinocytes; Keratins; Membrane Proteins; Nasopharyngeal Neoplasms; Transfection; Viral Proteins

A panel of 12 antibodies was used to further characterize the immunohistochemical staining profile of olfactory neuroblastoma. The following results were obtained for the 11 neoplasms that were immunostained: neuron-specific enolase 11/11(+), S-100 protein 8/11(+), microtubule-associated protein-2 8/11(+), class III beta-tubulin isotype 9/11(+), neurofilament 200 kD 8/11(+), synaptophysin 7/11(+), glial fibrillary acidic protein 1/11(+), chromogranin A 1/11(+), vimentin 1/11(+), keratin (CAM 5.2) 4/11(+), keratin (AEI/AE3) 0/11(+), and epithelial membrane antigen 0/11(+). Expression of two intermediate filaments was found in 4 of the 11 tumors. The authors' data showing that 72% of olfactory neuroblastomas were S-100 protein positive and only one was immunoreactive for glial fibrillary acidic protein agree with other published immunohistochemical studies. With only a single exception, each of the 11 neoplasms was labeled with one or more antibodies that detect neuronal cytoskeletal proteins (class III beta-tubulin isotype, microtubule-associated protein-2, neurofilament 200 kD). These immunohistochemical results are complementary to the reported electron microscopic findings of intermediate filaments and microtubules in olfactory neuroblastomas.

Topics: Adult; Aged; Chromogranin A; Chromogranins; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Membrane Proteins; Microtubule-Associated Proteins; Middle Aged; Mucin-1; Nasopharyngeal Neoplasms; Neuroectodermal Tumors, Primitive, Peripheral; Phosphopyruvate Hydratase; S100 Proteins; Synaptophysin; Tubulin; Vimentin

An epithelial tumor cell line, CG1, was established from human nasopharyngeal carcinoma tissues. The CG1 cells are of an epithelial origin as shown by their reactivities with the epithelial-specific antikeratin antibodies and by the presence of the desmosome structure at cell-cell junctions. CG1 cells possess characteristics of tumor cells because these cells are tumorigenic in nude mice and also have reduced serum requirements for in vitro cultivation. The doubling time of CG1 cells is 20 h and these cells have been successfully cultured in vitro for more than 200 generations. The average chromosome number of these cells is 60. Slot and Southern blot hybridizations showed the presence of Epstein-Barr virus-DNA sequences in CG1 cells. This cell line provides us an in vitro system for the study of the role of Epstein-Barr virus in nasopharyngeal carcinoma.

Topics: Animals; Carcinoma, Squamous Cell; Cell Division; Chromosome Aberrations; Chromosome Disorders; Desmosomes; DNA, Viral; Epithelium; Herpesvirus 4, Human; Humans; Karyotyping; Keratins; Mice; Nasopharyngeal Neoplasms; Neoplasm Transplantation; Tumor Cells, Cultured

Forty nasopharyngeal carcinomas (NPC) were studied by immunohistochemistry using an antibody to involucrin and the following three keratin antibodies: (1) an antibody to low molecular weight keratin reactive with nonsquamous epithelium, (2) a high molecular weight keratin antibody reactive with suprabasal squamous epithelium, and (3) a keratin antibody reactive with full thickness stratified epithelium. In its pattern of reactivity, the last antibody overlaps the low and high molecular weight keratin antibodies and is used as a broad spectrum keratin antibody. By World Health Organization (WHO) classification, the cases in this article included eight keratinizing squamous cell carcinomas, eight nonkeratinizing carcinomas, 20 undifferentiated carcinomas, and four adenocarcinomas. The antibody to broad spectrum keratin had an overall sensitivity of 87.5% and was positive in all eight keratinizing squamous cell carcinomas, seven nonkeratinizing carcinomas (87.5%), 18 undifferentiated carcinomas (90%), and two adenocarcinomas (50%). Low molecular weight keratin antibody stained one additional NPC, which was negative when broad spectrum keratin antibody was used. Involucrin and high molecular weight keratin antibodies demonstrated near parallel staining in all histologic classes; there was marked localization to areas of squamous differentiation. While involucrin is a marker for foci of greater squamous differentiation, broad spectrum keratin antibody may aid in the diagnosis of all histologic subtypes of NPC.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antibody Specificity; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Protein Precursors

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Nasopharyngeal Neoplasms; Staining and Labeling; Vimentin

Chondroid chordomas are shown to possess cytokeratins and to stain with HMFG-2 as do ordinary chordomas. These findings support the concepts that these neoplasms are a variant of chordoma and that they are unrelated to myxoid chondrosarcoma.

Topics: Antigens, Neoplasm; Chordoma; Humans; Keratins; Membrane Glycoproteins; Mucin-1; Nasopharyngeal Neoplasms; Skull Neoplasms; Sphenoid Bone

One hundred and one nasopharyngeal malignancies, clinically accepted and treated as carcinomas, were histologically reviewed. Originally, all of them had been given the histopathological diagnosis of carcinoma or possible carcinoma. A wide variety of diagnostic formulations had been used, some of them inconclusive. The review was based on strict morphological WHO criteria, and a definite diagnosis was attained in most cases. Three of the neoplasms, however, did not fulfil the criteria of carcinoma, and were given the diagnosis of malignant tumour, probable lymphoma. Immunohistochemistry with routinely processed tissue was performed on 69 of the poorly differentiated non-keratinizing neoplasms, including the three possible non-Hodgkin's malignant lymphomas. The neoplasms were positive for cytokeratin PKK1 with four exceptions: the three possible lymphomas and a large cell tumour with epithelial growth and prominent nucleoli which was found to be positive only for neurone-specific enolase. Two of three possible lymphomas were verified as such by being positive for leucocyte common antigen. This study showed that the WHO classification is quite useful when strictly applied. The histopathological diagnosis of this category of neoplasms can easily be confirmed by immunohistochemistry on routinely processed material and this adjunct can usually resolve questionable cases.

Topics: Alkaline Phosphatase; Antibodies, Monoclonal; Humans; Immunohistochemistry; Keratins; Nasopharyngeal Neoplasms; Staining and Labeling

Different tumours of the head and neck were analysed by immunohistochemistry. The distribution pattern of several intermediate filaments was studied. Keratin filaments were typical of carcinomas, whereas vimentin filaments were typical of mesenchymal tumours of different origin. The advances of this new technique of "tumour typing" are discussed.

Topics: Carcinoma, Basal Cell; Cytoskeleton; Diagnosis, Differential; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Lymphoma; Melanoma; Mouth Neoplasms; Nasopharyngeal Neoplasms; Neuroma, Acoustic; Oropharyngeal Neoplasms; Tonsillar Neoplasms; Vimentin

Papillomas (40) and squamous cell carcinomas (75) were examined for the presence of three keratin proteins with the use of an immunohistochemical technique. Polyclonal keratin antibody (TK, detecting 41 to 65 kDa keratin) and monoclonal antibodies KL1 and PKK1 (55 to 57 kDa and 41 to 56 kDa, respectively) were used. Squamous epithelium in normal oral mucosa showed marked TK staining in cells of upper strata and relatively slight staining in basal layer cells, moderate KL1 staining in spinous and granular layers and was negative in basal cells. Positive PKK1 staining was noted in cells of the basal layer. Columnar epithelium in the nasal mucosa showed TK staining in all layers, KL1 staining on the apical side of epithelial cells and trace or negative staining in basal layer cells. There was moderate PKK1 staining along the apical side of cells and variable staining in basal cells. Keratin distribution in oral papillomas was similar to that in normal oral epithelium, whereas in nasal and nasopharyngeal papillomas, keratin distribution was restricted to the upper layers. Tonsillar papillomas showed a strong TK reaction, negative KL1 in upper layer cells, and marked PKK1 staining in basal cells. Well-keratinized squamous carcinomas indicated an irregular TK distribution and decreased KL1 and negative PKK1 stainings. Intermediate and poorly differentiated keratinizing squamous carcinoma showed irregular staining patterns for the three classes of keratins studied. Immunohistochemically detectable keratins utilizing monoclonal antibodies were described as useful markers of epithelial tumors of squamous origin. Keratin expression within benign tumors was related to normal regional distribution, whereas in malignant tumors, keratin distribution was irregular in its distribution profile.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Keratins; Mouth Mucosa; Mouth Neoplasms; Nasal Mucosa; Nasopharyngeal Neoplasms; Papilloma

Eighteen examples of nasopharyngeal carcinoma (NPC), a tumor with potential diagnostic difficulty, were studied retrospectively. Using the WHO classification, 16 cases were undifferentiated carcinoma (UC). Immunohistochemistry for each tumor was performed on paraffin sections using two commercially available polyclonal antisera and a monoclonal antibody, AE-1. Method 1 used trypsinization, overnight incubation with the primary antibody and the avidin-biotin complex (ABC) technic. Method 2 used a 20-minute incubation with the primary antibody without trypsinization and employed the peroxidase-antiperoxidase (PAP) technic. Method 2 is the one most frequently employed by pathologists who use immunohistochemistry as a diagnostic aid. Method 1 gave clear positive results in each case with antibody AE-1 and, in most cases, with the polyclonal antisera. Electron microscopy in 10 cases demonstrated desmosomes in each case and easily demonstrable tonofilaments in five. The results of this study indicate that in the diagnosis of UC, the most common variant of NPC, squamous differentiation can be documented readily by electron microscopy and immunohistochemistry for keratin proteins. With the latter, optimization of technic is essential for reliable results.

Topics: Adult; Aged; Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Middle Aged; Nasopharyngeal Neoplasms; Retrospective Studies

Immunohistochemical studies using antisera to keratin and secretory component (SC) and monoclonal antibody against leukocyte common antigen (LCA) were performed on 92 biopsy and autopsy specimens taken from 65 patients with nasopharyngeal carcinoma. Five biopsy specimens from malignant lymphoma of the nasopharynx and tonsil, and 20 biopsy specimens of nasopharyngeal epithelium were also included in the study. Keratin was positively stained in all squamous cell carcinomas and nonkeratinizing carcinomas, and 38 of 46 undifferentiated carcinomas (82.6%), but in no malignant lymphomas. LCA was intensely stained in all malignant lymphoma, but in no nasopharyngeal carcinomas. SC was positively stained in two of the 46 undifferentiated carcinomas (4.3%). Nasopharyngeal carcinoma is a definite malignant epithelial neoplasm and can be distinguished from malignant lymphoma by immunostaining for keratin and LCA. Some undifferentiated carcinoma may show cellular differentiation toward ciliated epithelium.

Topics: Adolescent; Adult; Aged; Antigens; Carcinoma; Carcinoma, Squamous Cell; Child; Female; Histocompatibility Antigens; Histocytochemistry; Humans; Immunoenzyme Techniques; Immunoglobulin Fragments; Keratins; Leukocyte Common Antigens; Leukocytes; Lymphoma; Male; Middle Aged; Nasopharyngeal Neoplasms; Secretory Component

We investigated the value of prekeratin immunostaining in establishing the diagnosis of undifferentiated carcinoma of the nasopharyngeal type (lymphoepithelioma). As in squamous cell carcinoma of the nasopharynx, all seven lymphoepithelial carcinomas stained for prekeratin whereas other look-alike but histogenetically different neoplasms (malignant lymphoma, esthesioneuroblastoma, and small round cell sarcomas) did not stain. In addition to confirming the squamous epithelial nature of lymphoepithelioma, our findings indicated that immunoperoxidase staining for prekeratin is a useful diagnostic tool in the differential diagnosis of nasopharyngeal carcinomas in general and lymphoepithelioma in particular.

Topics: Animals; Antibodies; Carcinoma; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Nasopharyngeal Neoplasms; Protein Precursors; Rabbits

Two cases of olfactory neuroblastoma mixed with other neoplastic elements are reported. One tumor contained foci of adenocarcinoma and of ganglioneuroblastoma in addition to an undifferentiated small cell component consistent with neuroblastoma; the other tumor histologically resembled small cell undifferentiated carcinoma with foci of squamous differentiation, but was shown by electron microscopy to be neuroblastoma. The histogenesis and treatment of mixed tumors of this type are discussed.

Topics: Adenocarcinoma; Aged; Carcinoma; Carcinoma, Small Cell; Cytoplasm; Humans; Keratins; Male; Nasopharyngeal Neoplasms; Neuroblastoma; Nose Neoplasms

Nasopharyngeal carcinoma (NPC) provides a unique opportunity to evaluate distinctive epidemiologic features and a possible etiologic relationship with Epstein-Barr virus (EBV) in human malignancy. The lack of a uniformly accepted pathologic classification for NPC has limited the application of this data, although the World Health Organization (WHO) developed a classification that may solve this problem. Monoclonal keratin antibodies were used for staining of NPC for evaluation of its assistance in diagnosis and classification. In the present immunohistochemical study, monoclonal keratin antibodies, designated AE1, AE2, and AE3, and a polyclonal keratin antibody (RAK) were used for study of the presence of keratin in 121 cases of NPC obtained from China and the United States. AE1 monoclonal antibody, which recognizes keratin protein classes 56.5K, 50K, and 40K, was shown to be the most sensitive and specific for NPC tumor cells among the keratin antibodies studied. In addition, some different keratin expression patterns could be identified between different kinds of epithelium and different tumor groups, with possible relevance to the histogenesis of the histologic subtypes of NPC.

Topics: Antibodies, Monoclonal; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Nasopharyngeal Neoplasms; Nasopharynx

Immunocytochemical stains for three epithelial cell markers--keratin, epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA)--have been examined on paraffin-embedded material from 14 patients with nasopharyngeal carcinoma (NPC). Tumour cells staining positively for keratin were found in all cases and for EMA in eight; two tumours contained CEA-positive cells. Seven cases of Hodgkin's disease and 24 non-Hodgkin's lymphomas were uniformly negative. Keratin is the most reliable epithelial marker for identifying NPC and excluding lymphoma. The regular finding of stainable keratin in non-keratinising and anaplastic NPC supports the view that NPC is a homogeneous group exhibiting variable degrees of squamous differentiation.

Topics: Antigens; Carcinoembryonic Antigen; Carcinoma; Cell Membrane; Diagnosis, Differential; Epithelium; Hodgkin Disease; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Nasopharyngeal Neoplasms

Forty cases of nasopharyngeal neoplasia were analyzed using immunohistochemical staining employing keratin antibodies. Using this probe the tumors were classified as being keratin-positive or negative. In this study, all squamous cell carcinomas labeled with keratin antibodies whether they were classified as keratinizing or nonkeratinizing by usual staining methods. In contrast, lymphoid and mesenchymal tumors of the nasopharynx did not label with keratin antibodies. Thus, the presence of keratin proteins as detected by immunohistochemical means on paraffin-embedded tissues appears to be a useful, reliable, and sensitive method for aiding in the accurate diagnosis and classification of nasopharyngeal neoplasms.

Topics: Antibodies; Carcinoma; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Humans; Immunoenzyme Techniques; Keratins; Nasopharyngeal Neoplasms

Eight cases of primary and metastatic nasopharyngeal lymphoepithelioma and four cases of malignant lymphoma of the pharyngeal region were studied for the presence of keratin by indirect immunofluorescence microscopy. The results showed that all the cases of primary and metastatic lymphoepithelioma contained keratin-positive cells, whereas all the lymphomas were negative for keratin. Anti-keratin antibody thus seems to be a valuable aid in the differential diagnosis between lymphoepithelioma and lymphoma.

Topics: Carcinoma, Squamous Cell; Diagnosis, Differential; Fluorescent Antibody Technique; Histocytochemistry; Humans; Keratins; Lymphoma; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Pharyngeal Neoplasms

Nonglandular carcinomas of the nasopharynx originate in the epithelium of that anatomical region. Although numerous morphological patterns exist at the level observable by light microscopy, ultrastructurally, all have features of squamous-cell carcinoma. The most useful and consistent classification on the basis of light microscopy is that which separates keratinizing squamous carcinomas from nonkeratinizing carcinomas. Approximately 25% of tumours have abundant and easily recognized keratin. The nonkeratinizing types are more confusing, since many variants exist, both from tumour to tumour and, frequently, within the same tumour. Variable tissue reactions to infiltrating tumours, ranging from marked desmoplasia to complete absence of reaction, add to the confusion. The descriptive names applied to the variants of nonkeratinizing squamous carcinomas are well engraved in medical communications, and there is little chance that they will be abandoned.

Topics: Carcinoma; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Epithelium; Humans; Keratins; Nasopharyngeal Neoplasms; Nasopharynx

Topics: Biopsy; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cell Differentiation; Cell Nucleolus; Cell Nucleus; Chromatin; Cytoplasm; Desmosomes; Golgi Apparatus; Humans; Keratins; Microscopy, Electron; Mitochondria; Mononuclear Phagocyte System; Nasopharyngeal Neoplasms; Ribosomes

Topics: Biopsy; Carcinoma, Squamous Cell; Cell Nucleus; Cells, Cultured; Desmosomes; Epithelial Cells; Fibroblasts; Herpesviridae; Humans; Keratins; Lymphocyte Activation; Lymphocytes; Microscopy, Electron; Nasal Mucosa; Nasopharyngeal Neoplasms