Nasopharyngeal carcinoma cell screening based on the electroporation-SERS spectroscopy.

Nasopharyngeal carcinoma (NPC) is a malignant tumor in head and neck. Early diagnosis can effectively improve the survival rate of patients. Nasopharyngeal exfoliative cytology, as a convenient and noninvasive auxiliary diagnostic method, is suitable for the population screening of NPC, but its diagnostic sensitivity is low. In this study, an electroporation-based SERS technique was proposed to detect and screen the clinical nasopharyngeal exfoliated cell samples. Firstly, nasopharyngeal swabs was used to collected the nasopharyngeal exfoliated cell samples from NPC patients (n = 54) and healthy volunteers (n = 60). Then, gold nanoparticles, as the Raman scattering enhancing substrates, were rapidly introduced into cells by electroporation technique for surface-enhanced Raman scattering (SERS) detection. Finally, SERS spectra combined with principal component analysis (PCA) and linear discriminant analysis (LDA) were employed to diagnose and distinguish NPC cell samples. Raman peak assignments combined with spectral differences reflected the biochemical changes associated with NPC, including nucleic acid, amino acid and carbohydrates. Based on the PCA-LDA approach, the sensitivity, specificity and accuracy of 98.15 %, 96.67 % and 97.37 %, respectively, were achieved for screening NPC. This study offers valuable assistance for noninvasive NPC auxiliary diagnosis, and has grate potential in expanding the application of the SERS technique in clinical cell sample testing.

Shifted-excitation Raman difference spectroscopy for improving in vivo detection of nasopharyngeal carcinoma.

A strong fluorescence background is one of the common interference factors of Raman spectroscopic analysis in biological tissue. This study developed an endoscopic shifted-excitation Raman difference spectroscopy (SERDS) system for real-time in vivo detection of nasopharyngeal carcinoma (NPC) for the first time. Owing to the use of the SERDS method, the high-quality Raman signals of nasopharyngeal tissue could be well extracted and characterized from the complex raw spectra by removing the fluorescence interference signals. Significant spectral differences relating to proteins, phospholipids, glucose, and DNA were found between 42 NPC and 42 normal tissue sites. Using linear discriminant analysis, the diagnostic accuracy of SERDS for NPC detection was 100%, which was much higher than that of raw Raman spectroscopy (75.0%), showing the great potential of SERDS for improving the accurate in vivo detection of NPC.

Expression of ANCR in nasopharyngeal carcinoma patients and its clinical significance.

ABSTRACT: Anti-differentiation non-coding RNA (ANCR), a long non-coding RNA, is involved in the development, progression and metastasis of various human cancers. However, its clinical significance in nasopharyngeal carcinoma (NPC) still remains unknown. This study aimed to investigate ANCR expression and its clinical significance in NPC.Totally, 96 NPC tissues and 24 non-cancerous nasopharyngeal mucosa tissues were used. The levels of ANCR were determined by qRT-PCR. Relationship of ANCR with patient clinical characteristics, disease-free survival and overall survival (OS) was evaluated.ANCR expression was increased in NPC tissues compared to non-cancerous nasopharyngeal mucosae. ANCR expression was significantly related to lymph node metastasis, clinical stage, and tumor differentiation (P < .05). Kaplan-Meier survival analysis revealed that high level of ANCR expression was significantly associated with poor disease-free survival but not with OS in NPC patients. Univariate analysis showed a significant association between increased ANCR expression and adverse OS (P < .05), but multivariate analysis suggested that ANCR could not be used as an independent prognostic factor for NPC patients.ANCR is involved in the development and progression of NPC, but whether it can be used as an effective therapeutic target for NPC needs further study.

Expression of potential therapeutic target SSTR2a in primary and metastatic non-keratinizing nasopharyngeal carcinoma.

Somatostatin receptor 2a (SSTR2a) is an important diagnostic and scintigraphic marker in several tumors, as well as a potential therapeutic target. However, the expression and clinicopathologic significance of SSTR2a in nasopharyngeal carcinoma (NPC) remain unknown. The expression of SSTR2a was retrospectively analyzed in a large series of NPC tissue samples (106 primary NPC samples, comprising 99 primary non-keratinizing NPC (NK-NPC) and 7 keratinizing NPC (K-NPC) samples, and 41 metastatic NPC samples) by immunohistochemistry, with 24 cases of normal nasopharyngeal mucosa tissues used as a control group. Normal epithelia in nasopharyngeal mucosa were negative for SSTR2a in all 24 cases. The expression of SSTR2a in primary NPC was correlated to the histological subtype. Most cases of primary NK-NPC showed expression of SSTR2a (93.9%, 93/99 cases). The percentage of SSTR2a-positive tumor cells ranged from 10 to 100%, while the intensity ranged from 2+ to 4+. None of the primary K-NPC samples showed SSTR2a expression (0/7, 100%). All cases of NPC showed negative expression of other neuroendocrine markers, including synaptophysin, chromogranin A, and CD56. Of all 41 cases of metastatic NK-NPC lesions, SSTR2a expression is concordant with that of the primary lesions, which shows statistical significance (p < 0.001). Our observations expand the spectrum of recognized SSTR2a-positive tumors and demonstrate for the first time that SSTR2a is frequently expressed in primary and metastatic NK-NPC, highlighting its potential as a scintigraphic and therapeutic target in this disease.

Adenocarcinoma papilar de nasofaringe de bajo grado "thyroid-like". Caso clínico y revisión de la literatura / Low-grade papillary adenocarcinoma of nasopharynx. Case report and review of the literatura

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Expression of LEF1 and TCF1 (TCF7) proteins associates with clinical progression of nasopharyngeal carcinoma.

AIMS: Our previous study has demonstrated that ß-catenin pathway was abnormally activated in nasopharyngeal carcinoma (NPC). The purposes of the present study are to investigate whether the alterations of LEF1 and TCF1 (TCF7) proteins, the important components of the canonical Wnt/ß-catenin pathway, are associated with clinicopathological features and prognostic implications. METHODS: We collected 391 cases of NPC, 53 non-cancerous control nasopharyngeal mucosa and 28 pairs of NPC and their matched metastases, detected expression of LEF1 and TCF1 (TCF7) proteins in these tissues by immunohistochemistry.  RESULTS: Results showed that there were significantly increased expression of both LEF1 and TCF1 (TCF7) proteins and coexpression of LEF1 and TCF1 (TCF7) in NPC than these in non-cancerous nasopharyngeal mucosa (all p<0.001), as well as LEF1 and coexpression of LEF1 and TCF1 (TCF7) in matched metastasis NPCs than these in the primary NPCs (p=0.003 and p=0.014, respectively). In addition, expression of LEF1 and the coexpression of LEF1 and TCF1 (TCF7) proteins were positively correlated with lymph node metastasis (p=0.001 and p=0.020, respectively), advanced clinical stage (p<0.003 and p=0.027, respectively) and poor survival status of patients with NPC (p<0.001 and p=0.004, respectively). Moreover, multivariate Cox regression analysis identified that the positive expression of LEF1 was the independent poor prognostic factor for overall survival of patients with NPC (p<0.001). CONCLUSIONS: The expression of LEF1 associated positively with TCF1 (TCF7) and clinical progression of NPC, and positive expression of LEF1 protein may act as valuable independent biomarker to predict poor prognosis for patients with NPC.

p53R2 as a novel prognostic biomarker in nasopharyngeal carcinoma.

BACKGROUND: p53R2 is a target of p53 gene, which is essential for DNA repair, mitochondrial DNA synthesis, protection against oxidative stress, chromosomal instability, chronic inflammation and tumorigenesis. This study is aimed to investigate the expression of ribonucleotide reductase (RR) subunit p53R2 in nasopharyngeal carcinoma and its significance in the prognosis. METHODS: The expression levels of p53R2 in 201 patients with NPC were examined by immunohistochemical assay. The correlations of p53R2 expression and clinicopathological features of nasopharyngeal carcinoma patient were analysed by chi-square test. The Kaplan-Meier survival analysis and Cox multivariate regression model were used to analyze the prognostic significance of the patients with NPC. RESULTS: Immunohistochemical results showed that p53R2 was positively expressed in 92.5% (186/201) of nasopharyngeal carcinoma and the high expression rate was 38.3% (77/201). Further analysis observed that the negative correlation between expression of p53R2 and pT status had statistical significance (P < 0.05). Kaplan-Meier survival analysis found that the mean survival time of patients with high expression of p53R2 was 143.32 months, while the patients with low expression level of p53R2 was 121.63 months (P < 0.05). Cox regression analysis suggested that p53R2 protein expression could be used as an independent prognostic factor for nasopharyngeal carcinoma (P < 0.05). CONCLUSIONS: This study drew a conclusion that p53R2 could be used as a prognostic biomarker indicative of the favorable outcome for patients with nasopharyngeal carcinoma.

Real-time In vivo Diagnosis of Nasopharyngeal Carcinoma Using Rapid Fiber-Optic Raman Spectroscopy.

We report the utility of a simultaneous fingerprint (FP) (i.e., 800-1800 cm-1) and high-wavenumber (HW) (i.e., 2800-3600 cm-1) fiber-optic Raman spectroscopy developed for real-time in vivo diagnosis of nasopharyngeal carcinoma (NPC) at endoscopy. A total of 3731 high-quality in vivo FP/HW Raman spectra (normal=1765; cancer=1966) were acquired in real-time from 204 tissue sites (normal=95; cancer=109) of 95 subjects (normal=57; cancer=38) undergoing endoscopic examination. FP/HW Raman spectra differ significantly between normal and cancerous nasopharyngeal tissues that could be attributed to changes of proteins, lipids, nucleic acids, and the bound water content in NPC. Principal components analysis (PCA) and linear discriminant analysis (LDA) together with leave-one subject-out, cross-validation (LOO-CV) were implemented to develop robust Raman diagnostic models. The simultaneous FP/HW Raman spectroscopy technique together with PCA-LDA and LOO-CV modeling provides a diagnostic accuracy of 93.1% (sensitivity of 93.6%; specificity of 92.6%) for nasopharyngeal cancer identification, which is superior to using either FP (accuracy of 89.2%; sensitivity of 89.9%; specificity of 88.4%) or HW (accuracy of 89.7%; sensitivity of 89.0%; specificity of 90.5%) Raman technique alone. Further receiver operating characteristic (ROC) analysis reconfirms the best performance of the simultaneous FP/HW Raman technique for in vivo diagnosis of NPC. This work demonstrates for the first time that simultaneous FP/HW fiber-optic Raman spectroscopy technique has great promise for enhancing real-time in vivo cancer diagnosis in the nasopharynx during endoscopic examination.

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma with squamous differentiation: a novel histological finding.

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is an extremely rare neoplasm originating from the nasopharyngeal surface epithelium. Histopathologically, TL-LGNPPA is characterized by cuboidal/columnar tumor cells forming papillary fronds and thyroid transcription factor-1 (TTF-1) expression resembling papillary thyroid carcinoma. To date, the recorded histological features of TL-LGNPPA have been almost uniform, and the range of histological variations in this tumor type has not been sufficiently understood. Here, we report on a 68-year-old man with TL-LGNPPA. Microscopic examination of the resected tumor revealed findings typical of papillary adenocarcinoma of this type, and moreover, this case showed scattered squamous cell foci as a hitherto unreported finding. The squamous cells showed no obvious nuclear atypia or proliferating activity, and their presence was similar to the "squamous metaplasia" of papillary thyroid carcinoma. Immunohistochemically, p40 and TTF-1 coexpression was observed in the squamous cell nuclei, indicating their origin from the glandular tumor cells of TL-LGNPPA.

Vitepyrroloids A-D, 2-Cyanopyrrole-Containing Labdane Diterpenoid Alkaloids from the Leaves of Vitex trifolia.

Vitepyrroloids A-D (1-4), four new 2-cyano-substituted pyrrole-ring-containing labdane diterpenoids, were isolated from the leaves of Vitex trifolia. Their structures were elucidated based on spectroscopic data analysis. The absolute configuration of compound 1 was determined by X-ray diffraction. Compounds 1-4 are unprecedented labdane diterpenoids featuring a 2-cyano-substituted pyrrole ring. Compound 1 showed cytotoxic activity against a human nasopharyngeal carcinoma cell line (CNE1) with an IC50 value of 8.7 µM.

The increased expression of TCF3 is correlated with poor prognosis in Chinese patients with nasopharyngeal carcinoma.

OBJECTIVES: Regulatory factors controlling stem cell identity and self-renewal are often active in aggressive cancers and are thought to promote cancer growth and progression. B-cell-specific transcription factor 3 (TCF3/E2A) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family that is central to regulating epidermal and embryonic stem cell identity. It has been reported that TCF3 was connected with the development and progression of a number of human cancers. In this study, we aimed to identify the expression of TCF3 in human nasopharyngeal carcinoma (NPC) and evaluate its clinical significance. DESIGN: To investigate the expression of TCF3 in NPC and its relationship to prognosis. SETTING: An in vitro study. MAIN OUTCOME MEASURES: We analysed the expression of TCF3 in NPC and in non-tumourous nasopharyngeal tissues by quantitative RT-PCR and Western blotting. The expression patterns of TCF3 in 117 archived paraffin-embedded NPC specimens were characterised by immunohistochemistry, and the correlation between the TCF3 protein expression and the clinicopathological features of NPC was analysed. RESULTS: We observed that TCF3 had a higher expression in NPC than in non-tumourous nasopharyngeal tissues of 117 archived paraffin-embedded NPC specimens, and 80 (68.4%) biopsy tissues revealed high levels of TCF3 expression. Furthermore, statistical analyses demonstrated that the increased expression of TCF3 was closely related to clinical stage, locoregional recurrence and distant metastasis of NPC. NPC patients with high levels of TCF3 expression had a shorter survival time, whereas patients with lower levels of TCF3 expression survived longer. Moreover, multivariate analysis suggested that the upregulation of TCF3 was a critical prognostic factor for NPC. CONCLUSIONS: Our observations suggest, for the first time, that TCF3 is significantly associated with the development and progression of NPC, which can be used as an important prognostic marker for patients with NPC and may be an effective target for the treatment of NPC.

Early discrimination of nasopharyngeal carcinoma based on tissue deoxyribose nucleic acid surface-enhanced Raman spectroscopy analysis.

Surface-enhanced Raman spectroscopy (SERS) was employed to detect deoxyribose nucleic acid (DNA) variations associated with the development of nasopharyngeal carcinoma (NPC). Significant SERS spectral differences between the DNA extracted from early NPC, advanced NPC, and normal nasopharyngeal tissue specimens were observed at 678, 729, 788, 1337, 1421, 1506, and 1573??cm?1, which reflects the genetic variations in NPC. Principal component analysis combined with discriminant function analysis for early NPC discrimination yielded a diagnostic accuracy of 86.8%, 92.3%, and 87.9% for early NPC, advanced NPC, and normal nasopharyngeal tissue DNA, respectively. In this exploratory study, we demonstrated the potential of SERS for early detection of NPC based on the DNA molecular study of biopsy tissues.

Selenium-binding protein 1 in head and neck cancer is low-expression and associates with the prognosis of nasopharyngeal carcinoma.

BACKGROUND: Selenium-binding protein 1 (SELENBP1) expression is reduced markedly in many types of cancers and low SELENBP1 expression levels are associated with poor patient prognosis. METHODS: SELENBP1 gene expression in head and neck squamous cell carcinoma (HNSCC) was analyzed with GEO dataset and characteristics of SELENBP1 expression in paraffin embedded tissue were summarized. Expression of SELENBP1 in nasopharyngeal carcinoma (NPC), laryngeal cancer, oral cancer, tonsil cancer, hypopharyngeal cancer and normal tissues were detected using immunohistochemistry, at last, 99 NPC patients were followed up more than 5 years and were analyzed the prognostic significance of SELENBP1. RESULTS: Analysis of GEO dataset concluded that SELENBP1 gene expression in HNSCC was lower than that in normal tissue (P < 0.01), but there was no significant difference of SELENBP1 gene expression in different T-stage and N-stage (P > 0.05). Analysis of pathological section concluded that SELENBP1 in the majority of HNSCC is low expression and in cancer nests is lower expression than surrounding normal tissue, even associated with the malignant degree of tumor. Further study indicated the low SELENBP1 expression group of patients with NPC accompanied by poor overall survival and has significantly different comparing with the high expression group. CONCLUSION: SELENBP1 expression was down-regulated in HNSCC, but has no associated with T-stage and N-stage of tumor. Low expression of SELENBP1 in patients with NPC has poor over survival, so SELENBP1 could be a novel biomarker for predicting prognosis.

[Rare earth elements contents and distribution characteristics in nasopharyngeal carcinoma tissue].

OBJECTIVE: To investigate the rare earth elements(REEs) contents and distribution characteristics in nasopharyngeal carcinoma( NPC) tissue in Gannan region. METHOD: Thirty patients of NPC in Gannan region were included in this study. The REEs contents were measured by tandem mass spectrometer inductively coupled plasma(ICP-MS/MS) in 30 patients, and the REEs contents and distribution were analyzed. RESULT: The average standard deviation value of REEs in lung cancer and normal lung tissues was the minimum mostly. Light REEs content was higher than the medium REEs, and medium REEs content was higher than the heavy REEs content. REEs contents changes in nasopharyngeal carcinoma were variable obviously, the absolute value of Nd, Ce, Pr, Gd and other light rare earth elements were variable widely. The degree of changes on Yb, Tb, Ho and other heavy rare earth elements were variable widely, and there was presence of Eu, Ce negative anomaly(δEu=0. 385 5, δCe= 0. 523 4). CONCLUSION: The distribution characteristic of REEs contents in NPC patients is consistent with the parity distribution. With increasing atomic sequence, the content is decline wavy. Their distribution patterns were a lack of heavy REEs and enrichment of light REEs, and there was Eu , Ce negative anomaly.

The natural compound gambogic acid radiosensitizes nasopharyngeal carcinoma cells under hypoxic conditions.

AIMS: Hypoxia is an important factor that causes decreased local disease control as well as increased distant metastases and resistance to radiotherapy in patients with advanced nasopharyngeal carcinoma (NPC). Gambogic acid (GA), the major active ingredient of gamboge, exerts antitumor effects in vitro and in vivo. However, the molecular mechanism by which GA inhibits tumor radioresistance remains unclear. The present study aimed to investigate the radiosensitizing effects of GA on NPC and explore the underlying mechanisms. MATERIALS AND METHODS: CNE-1 and CNE-2 cells exposed to hypoxia and radiation were treated with GA at different concentrations. CCK-8 assay, clonogenic assay, and flow cytometry were performed to analyze cell proliferation, colony formation, apoptosis, and cell cycle. The expression levels of hypoxia-inducible factor-1α (HIF-1α), Bcl-2, Bax, caspase-3, cyclin B1/p-cdc2 and γ-H2AX were assessed using Western blot and/or immunofluorescence analysis. RESULTS: Results of the CCK-8 assay, clonogenic assay, and flow cytometry showed that treatment of NPC cells with growth-suppressive concentrations of GA resulted in G2/M phase arrest and apoptosis. Western blot analysis demonstrated that GA-induced cell cycle arrest and apoptosis in CNE-2 cells was associated with upregulated expression of caspase-3 and Bax and downregulated expression of Bcl-2 and cyclin B1/p-cdc2 in hypoxia. Treatment with GA markedly decreased the expression of HIF-1α under hypoxic conditions. CONCLUSIONS: The results of this study suggest that GA efficiently radiosensitizes NPC cells and the effect may be significant in hypoxic conditions.

Unusual coexistence of extramedullary plasmacytoma and nasopharyngeal carcinoma in nasopharynx.

Nasopharyngeal carcinoma (NPC) is an EBV-associated malignant tumor of nasopharynx. As extremely rare condition, the second primary cancer of nasopharynx can occur in NPC patients synchronously or subsequently. Extramedullary plasmacytoma (EMP) is a rare tumor and commonly originates in the head and neck region. However, there is no report to describe a collision tumor of NPC and EMP occurring in the same nasopharyngeal mass. We report here an unusual case of synchronous coexistence of NPC and EMP occurring in the nasopharynx of an old male patient. A 63-year-old male patient presented with a 3-month history of right-sided nasal obstruction and recently intermittent epistaxis without enlargement of cervical lymph nodes. The solitary mass of nasopharynx was found by radiological and nasopharyngeal examination. Histologically, the mass contained two separated portions and displayed typically histological features of NPC and EMP, respectively. In EMP portion, the tumor was composed of monomorphic plasmacytoid-appearing cells with immuno-positive to CD79a, CD138, CD38, MUM-1 and CD56, but lack immunoreactivity to pan-CK (AE1/AE3), CD20, CD21 and EBERs. In NPC portion, the tumor cells formed irregular-shaped islands with diffusely immuno-positive to pan-CK (AE1/AE3), EMA and EBERs, but lack expressions of lymphoplasmacytic markers. A diagnosis of simultaneous occurrence of EMP and NPC in nasopharynx was made. There was no evidence of tumor recurrence or metastasis 18-month follow-up after radiotherapy. To our knowledge, it may be the first case of coexistence of EMP and NPC synchronously. In addition, the histological differential diagnosis and relevant potential mechanism of this unusual collision tumor were also discussed.

A case of hepatocellular carcinoma in an elder man with metastasis to the nasopharynx.

The lung, bone, brain, etc are common metastatic sites of hepatocellular carcinoma. Nasopharynx metastasis of hepatocellular carcinoma rarely occurs and has not been reported yet. Here we report one case of nasopharynx metastasis from liver in a 50-year-old male patient who was diagnosed with primary hepatocellular carcinoma (nodular and diffuse-type) in 2014. 6 and underwent interventional therapy for two times afterward. However, he suffered from severe headache in 2014. 8, and head contrast-enhanced MRI scan did not show clues for brain or skulls metastasis. Then the lumbar puncture was performed to examine his cerebrospinal fluid (CSF). It showed that cerebrospinal fluid protein (AFP) was extremely higher than the normal level. Then, he developed left blepharoptosis, eye opening obstacle, impaired vision and dysphagia. Positron emission tomography CT (PET-CT) showed that there was multiple bone destruction in skull base, indicating the nasopharyngeal cancer which was proven to be the metastatic tumor from liver histologically by biopsy. Finally, this patient underwent radiotherapy (RT) of nasopharyngeal metastatic tumor and the local symptoms changed for the better.

BRCC3 acts as a prognostic marker in nasopharyngeal carcinoma patients treated with radiotherapy and mediates radiation resistance in vitro.

BACKGROUND: BRCC3 has been found to be aberrantly expressed in breast tumors and involved in DNA damage response. The contribution of BRCC3 to nasopharyngeal carcinoma prognosis and radiosensitivity is still unclear. METHODS: Immunohistochemical analysis of BRCC3 was carried out in 100 nasopharyngeal carcinoma tissues, and the protein level was correlated to patient survival. BRCC3 expression of nasopharyngeal carcinoma cell lines was determined by Western-blotting and real-time PCR. Additionally, the effects of BRCC3 knockdown on nasopharyngeal carcinoma cell clongenic survival, DNA damage repair, and cell cycle distribution after irradiation was assessed. RESULTS: The BRCC3 protein level was inversely correlated with nasopharyngeal carcinoma patient overall survival (P < 0.001) and 3-year loco-regional relapse-free survival (P = 0.034). Multivariate analysis demonstrated that BRCC3 expression was an independent prognostic factor (P = 0.010). The expression of BRCC3 was much higher in radioresistant nasopharyngeal carcinoma cells than in radiosensitive cells. Knockdown of BRCC3 increased the cell survival fraction, attenuated DNA damage repair and resulted in G2/M cell cycle arrest in radioresistant NPC cells. CONCLUSIONS: High BRCC3 expression in nasopharyngeal carcinoma patients is associated with poor survival. BRCC3 knockdown could abate the radioresistance in nasopharyngeal carcinoma cells. These findings suggest the utility of BRCC3 as a prognostic biomarker and novel target for nasopharyngeal carcinoma.

Expression patterns of claudins 1, 4, and 7 and their prognostic significance in nasopharyngeal carcinoma.

PURPOSE: Tight junction (TJ) proteins in the cells organize paracellular permeability, and they have a critical role in apical cell-to-cell adhesion and epithelial polarity. In our study, the expression patterns of claudins 1, 4, and 7 and their relationship with prognosis were determined in patients with nasopharyngeal carcinoma. METHODS: Claudins 1, 4, and 7 were stained immunohistochemically in 18 biopsy samples of nasopharyngeal carcinomas that included non-neoplastic surface epithelium and dysplastic epithelium in addition to the tumor tissue. The files of these patients were scanned and the stage of disease and treatment received were obtained along with demographic data such as age and gender. RESULTS: Overexpression of claudins 1, 4, and 7 in non-neoplastic surface epithelium was found in 14 (77.7%), 16 (88.8%), and 10 (55.5%) cases respectively; in dysplastic surface epithelium overexpression was found in 8 (44.4%), 13 (72.2%), and 4 (22.2%) cases, respectively; and in invasive tumor areas overexpression was found in 13 (72.2%), 9 (50%), and 10 (55.6%) cases respectively. Increased claudin 4 expression was related to advanced stage (p=0.014). There was a significant relationship determined between claudin 4 and 7 expression and decreased survival (p=0.018, p=0.024, respectively). CONCLUSION: The fact that a statistically significant relationship was found between claudin 4 expression and advanced stage, and similarly a statistically significant relationship was found between claudin 4 & 7 expression and decreased survival gives rise to thoughts that especially claudin 4 and 7 could have different tumorigenic effects on nasopharyngeal carcinoma besides their known adhesion characteristics.