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OSCC
Terms modified by OSCC Selected AbstractsOral lichen planus has a high rate of TP53 mutations.EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 3 2002A study of oral mucosa in Iceland Oral squamous cell carcinoma (OSCC) is a world-wide health problem. In addition to external exposure (smoking and alcohol), certain oral lesions may increase the risk of oral cancer (e.g. leukoplakia, erythroplakia, and oral lichen planus). TP53 has been implicated in OSCC, but there are limited studies of mutations in premalignant oral lesions. In this study, 55 samples from OSCC, 47 from hyperkeratotic (HK) oral mucosa, clinically diagnosed as white patches, 48 samples from oral lichen planus (OLP), and 12 biopsies from normal oral mucosa were studied immunohistochemically for expression of TP53 protein. From all the carcinoma samples and selected non-malignant samples showing moderate or strong TP53 protein expression, malignant cells or TP53-positive nuclei were microdissected and screened for mutations in exons 5,8 by constant denaturation gel electrophoresis. Moderate to strong TP53 protein staining was seen in 56% of OSCC, 32% of OLP but only in 13% of HK. All OLP samples showed a characteristic pattern of positive nuclei confined to the basal layer, whereas TP53 staining was seen in suprabasal nuclei in HK. Mutation rate was 11 out of 52 for OSCC, three out of 20 tested for HK and, remarkably, nine out 27 tested for OLP. There was no correlation between TP53 protein staining and TP53 mutations. No associations were found with anatomical sites or disease progression. The unexpectedly high mutation rate of OLP might explain the premalignant potential of this lesion. [source] Recurrent copy number gain of transcription factor SOX2 and corresponding high protein expression in oral squamous cell carcinomaGENES, CHROMOSOMES AND CANCER, Issue 1 2010Kolja Freier Gene copy number aberrations are involved in oral squamous cell carcinoma (OSCC) development. To delineate candidate genes inside critical chromosomal regions, array-CGH was applied to 40 OSCC specimens using a microarray covering the whole human genome with an average resolution of 1 Mb. Gene copy number gains were predominantly found at 1q23 (9 cases), 3q26 (11), 5p15 (13), 7p11 (7), 8q24 (17), 11q13 (15), 14q32 (8), 19p13 (8), 19q12 (7), 19q13 (8), and 20q13 (9), whereas gene copy number losses were detected at 3p21-3p12 (15), 8p32 (11), 10p12 (8), and 18q21-q23 (10). Subsequent mRNA expression analyses by quantitative real time polymerase chain reaction found high mRNA expression of candidate genes SOX2 in 3q26.33, FSLT3 in 19p13.3, and CCNE1 in 19q12. Tissue microarray (TMA) analyses in a representative OSCC collection found gene copy number gain for SOX2 in 52% (115/223) and for CCNE1 in 31% (72/233) of the tumors. Immunohistochemical analyses on TMA sections of the corresponding proteins detected high expression of SOX2 in 18.1% (49/271) and of CyclinE1 in 23.3% (64/275) of tumors analyzed. These findings indicate that SOX2 and CCNE1 might be activated via gene copy number gain and participate in oral carcinogenesis. The combination of array-CGH with TMA analyses allows rapid pinpointing of novel promising candidate genes, which might be used as therapeutic stratification markers or target molecules for therapeutic interference. © 2009 Wiley-Liss, Inc. [source] Recurrent coamplification of cytoskeleton-associated genes EMS1 and SHANK2 with CCND1 in oral squamous cell carcinomaGENES, CHROMOSOMES AND CANCER, Issue 2 2006Kolja Freier Chromosomal band 11q13 is frequently amplified in oral squamous cell carcinoma (OSCC) and assumed to be critically involved in tumor initiation and progression by proto-oncogene activation. Though cyclin D1 (CCND1) is supposed to be the most relevant oncogene, several additional putative candidate genes are inside this chromosomal region, for which their actual role in tumorigenesis still needs to be elucidated. To characterize the 11q13 amplicon in detail, 40 OSCCs were analyzed by comparative genomic hybridization to DNA microarrays (matrix-CGH) containing BAC clones derived from chromosomal band 11q13. This high-resolution approach revealed a consistent amplicon about 1.7 Mb in size including the CCND1 oncogene. Seven BAC clones covering FGF3, EMS1, and SHANK2 were shown to be frequently coamplified inside the CCND1 amplicon. Subsequent analysis of tissue microarrays by FISH revealed amplification frequencies of 36.8% (88/239) for CCND1, 34.3% (60/175) for FGF3, 37.4% (68/182) for EMS1, and 36.3% (61/168) for SHANK2. Finally, quantitative mRNA expression analysis demonstrated consistent overexpression of CCND1 in all tumors and of EMS1 and SHANK2 in a subset of specimens with 11q13 amplification, but no expression of FGF3 in any of the cases. Our study underlines the critical role of CCND1 in OSCC development and additionally points to the functionally related genes EMS1 and SHANK2, both encoding for cytoskeleton-associated proteins, which are frequently coamplified with CCND1 and therefore could cooperatively contribute to OSCC pathogenesis. © 2005 Wiley-Liss, Inc. [source] Incidence and patterns of regional metastasis in early oral squamous cell cancers: Feasibility of submandibular gland preservationHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2009Ali Razfar BS Abstract Background. We aimed to study the incidence of metastasis to the submandibular gland (SMG) and to establish the oncologic basis of SMG preservation in early-stage cancer of the oral cavity (OSCC). Methods. This was a retrospective study of 261 patients with OSCC treated primarily with surgery at a tertiary medical center. One hundred thirty-two early-stage (T1-2, N0) OSCCs were further analyzed. Results. The mean age was 59 years with male-to-female sex ratio of 1.4:1. Two hundred sixty-one neck dissections were performed with SMG removal in 253 patients. One patient with an advanced floor of mouth cancer had obvious infiltration of the SMG. Only 2.5% (3 of 116) patients with early-stage OSCC had level I metastasis; none had SMG metastases. Conclusion. SMG preservation in early cancers (T1-2, N0) of the oral cavity should be feasible unless there is evidence of direct invasion of the gland or close proximity of the cancer to it. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source] Invasive pattern grading score designed as an independent prognostic indicator in oral squamous cell carcinomaHISTOPATHOLOGY, Issue 2 2010Yun-Ching Chang Chang Y-C, Nieh S, Chen S-F, Jao S-W, Lin Y-L & Fu E (2010) Histopathology,57, 295,303 Invasive pattern grading score designed as an independent prognostic indicator in oral squamous cell carcinoma Aims:, To test the validity of an invasive pattern grading score (IPGS) developed for oral squamous cell carcinoma (OSCC) as a prognostic indicator and to elucidate the relationship between the IPGS and clinical parameters. Methods and results:, The IPGS was applied to a total of 153 cases of OSCC. There were significant correlations between IPGS and distant metastasis (P = 0.01) or recurrence (P = 0.001). However, there were no significant correlations between IPGS and gender, age, size or extent, location, status of lymph node metastasis, clinical staging, or histological grading. Cases of OSCC with higher IPGS were associated with poor patient survival (P < 0.001) and higher probability of tumour recurrence (P = 0.001). Intraobserver (, = 0.74) and interobserver agreement (, = 0.67) were very satisfactory. Conclusions:, Our study confirms the validity of the IPGS, an indicator that is simple and easy to use. IPGS not only provides histological assessment of biological behaviour, but also offers an independent prognostic factor that may influence the treatment of OSCC. [source] Tumor-stromal crosstalk in invasion of oral squamous cell carcinoma: a pivotal role of CCL7INTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Da-Woon Jung Abstract Recent studies have shown that stromal fibroblasts have a more profound influence on the initiation and progression of carcinoma than was previously appreciated. This study aimed at investigating the reciprocal relationship between cancer cells and their associated fibroblasts at both the molecular and cellular level in oral squamous cell carcinoma (OSCC). To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing cocultured OSCC cells and CAF with monoculture controls. Microarray and real-time PCR analysis identified marked upregulation of the chemokine (C-C motif) ligand 7 (CCL7) in cocultured CAF. ELISA showed an elevated level of CCL7 secretion from CAF stimulated by coculture with OSCC cells. CCL7 promoted the invasion and migration of OSCC cells, and the invasiveness was inhibited by treatment with CCL7 neutralizing antibody. OSCC cells were shown to express CCR1, CCR2 and CCR3, receptors for CCL7, by RT-PCR. In addition, treatment with anti-CCR1 or anti-CCR3 antibody inhibited CCL7-induced OSCC cell migration, implicating that CCL7 promotes cancer cell migration through CCR1 and CCR3 on OSCC cells. Cytokine antibody array analysis of the supernatant from OSCC cell culture revealed that interleukin-1, was an inducer of CCL7 secretion by CAF. This study confirms the reciprocal relationship of the molecular crosstalk regulating the invasion of OSCC and describes new potential targets for future therapy. [source] Lysyl oxidase expression is an independent marker of prognosis and a predictor of lymph node metastasis in oral and oropharyngeal squamous cell carcinoma (OSCC)INTERNATIONAL JOURNAL OF CANCER, Issue 11 2010Andrea Albinger-Hegyi Abstract Proteins of the lysyl oxidase (LOX) family are important modulators of the extracellular matrix. However, they have an important role in the tumour development as well as in tumour progression. To evaluate the diagnostic and prognostic value of the LOX protein in oral and oropharyngeal squamous cell carcinoma (OSCC) we performed QRT-PCR and immunohistochemical analysis on two tissue microarrays (622 tissue samples in total). Significantly higher LOX expression was detected in high grade dysplastic oral mucosa as well as in OSCC when compared to normal oral mucosa (P < 0.001). High LOX expression was correlated with clinical TNM stage (P = 0.020), lymph node metastases for the entire cohort (P < 0.001), as well as in the subgroup of small primary tumours (T1/T2, P < 0.001). Moreover, high LOX expression was correlated with poor overall survival (P = 0.004) and disease specific survival (P = 0.037). In a multivariate analysis, high LOX expression was an independent prognostic factor, predicting unfavourable overall survival. In summary, LOX expression is an independent prognostic biomarker and a predictor of lymph node metastasis in OSCC. Moreover, LOX overexpression may be an early phenomenon in the pathogenesis of OSCC and thus an attractive novel target for chemopreventive and therapeutic strategies. [source] Nm23-H1 expression of metastatic tumors in the lymph nodes is a prognostic indicator of oral squamous cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 2 2008Yi-Fen Wang Abstract We recently reported that low Nm23-H1 expression of primary oral squamous cell carcinoma (OSCC) was correlated with the occurrence of lymphatic metastasis. However, little is known about whether Nm23-H1 level of metastatic tumors in the cervical lymph nodes is reduced in comparison with primary oral cancers and its significance for patients' prognosis. By immunohistochemistry, we analyzed the Nm23-H1 expression in 52 pairs of OSCC specimens from primary oral cancers and their metastatic lymph nodes. Western blot analysis further confirmed the immunohistochemical interpretation. To verify the effects of Nm23-H1 on cell migration and invasion, we established several stable clones derived from a human OSCC cell line (SAS) by knockdown and overexpression. Wound-healing closure, transwell migration and invasion assays were performed to determine cell motility, migratory and invasive activities. Western blot analysis was carried out to evaluate cyclin A expression of OSCC cells with the altered Nm23-H1 levels following knockdown and overexpression. By immunohistochemistry, Nm23-H1 expression of metastatic lymph nodes was significantly lower than that of their primary oral cancers, supporting a role of Nm23-H1 in metastasis suppression. Negative Nm23-H1 interpretation of OSCC specimens, in either primary oral cancers or metastatic lymph nodes, indicated a poor survival outcome of patients. On the basis of in vitro studies of Nm23-H1 knockdown and overexpression, we demonstrated an inverse correlation between Nm23-H1 expression and the invasiveness of OSCC cells. Moreover, we observed the concomitant reduction in Nm23-H1 and cyclin A levels of metastatic tumors in both results of in vitro OSCC cells and ex vivo tumor specimens. © 2007 Wiley-Liss, Inc. [source] The involvement of hypoxia-inducible factor-1, in the susceptibility to ,-rays and chemotherapeutic drugs of oral squamous cell carcinoma cellsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2007Eri Sasabe Abstract The transcription factor hypoxia-inducible factor-1, (HIF-1,) is the key regulator that controls the hypoxic response of mammalian cells. The overexpression of HIF-1, has been demonstrated in many human tumors. However, the role of HIF-1, in the therapeutic efficacy of chemotherapy and radiotherapy in cancer cells is poorly understood. In this study, we investigated the influence of HIF-1, expression on the susceptibility of oral squamous cell carcinoma (OSCC) cells to chemotherapeutic drugs (cis -diamminedichloroplatinum and 5-fluorouracil) and ,-rays. Treatment with chemotherapeutic drugs and ,-rays enhanced the expression and nuclear translocation of HIF-1,, and the susceptibility of OSCC cells to the drugs and ,-rays was negatively correlated with the expression level of HIF-1, protein. The overexpression of HIF-1, induced OSCC cells to become more resistant to the anticancer agents, and down-regulation of HIF-1, expression by small interfering RNA enhanced the susceptibility of OSCC cells to them. In the HIF-1,-knockdown OSCC cells, the expression of P-glycoprotein, heme oxygenase-1, manganese-superoxide dismutase and ceruloplasmin were downregulated and the intracellular levels of chemotherapeutic drugs and reactive oxygen species were sustained at higher levels after the treatment with the anticancer agents. These results suggest that enhanced HIF-1, expression is related to the resistance of tumor cells to chemo- and radio-therapy and that HIF-1, is an effective therapeutic target for cancer treatment. © 2006 Wiley-Liss, Inc. [source] Oral squamous cell carcinoma and cultural oral risk habits in VietnamINTERNATIONAL JOURNAL OF DENTAL HYGIENE, Issue 3 2010SL Priebe To cite this article: Int J Dent Hygiene,8, 2010; 159,168 DOI: 10.1111/j.1601-5037.2010.00461.x Priebe SL, Aleksej,nien, J, Zed C, Dharamsi S, Thinh DHQ, Hong NT, Cuc TTK, Thao NTP. Oral squamous cell carcinoma and cultural oral risk habits in Vietnam. Abstract: Objectives:, In South-Central Asia, 80% of head and neck cancers are found in the oral cavity and oropharynx. In Vietnam, oral cancer is often not being detected until people experience debilitating circumstances to normal oral function. The aims of the study were to explore the patterns of oral squamous cell carcinoma (OSCC) and its risk indicators, the structure of oral health care in Vietnam and trends in prevalence of cultural risk habits in southern Vietnamese patients. Materials and Methods:, A retrospective clinical study was performed from 1 July 2005 to 1 April 2006 at Ho Chi Minh City Oncology hospital in Vietnam. Of the 161 cases, 147 subjects were diagnosed with OSCC, including 100 male and 47 female adults aged 24,85 years. Data were collected by a structured interview and clinical examination. Results:, Over 40% of the women with OSCC reported chewing betel quid and the most prevalent risk habit in males was smoking (91.0%). Daily alcohol use was reported by 79.0% of males and 2.1% of females. Two-thirds of the cases of OSCC were diagnosed at the 2nd and 3rd stage of cancer. The more advanced stages of cancer were observed in males than in females. The prevalence of tobacco and alcohol use in males with OSCC was higher in this study than in the previous Vietnamese studies. Conclusion:, High frequency of risk habits in both genders was reported in OSCC Vietnamese patients. A trend of increased tobacco and alcohol use was observed in male OSCC patients. A lower prevalence of later staging in Vietnam was observed in this study than in earlier studies. [source] TP53 mutations in clinically normal mucosa adjacent to oral carcinomasJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2010C. Thode J Oral Pathol Med (2010) 39: 662,666 Background:, The tumour-suppressor protein p53 often accumulates in histologically normal epithelium adjacent to oral squamous cell carcinomas (OSCC). We investigated whether this was associated with mutations in TP53, the gene for p53, and might implicate impending malignancy. Methods:, Specimens from 18 human squamous cell carcinomas were stained with monoclonal p53 antibodies. Positive cells were microdissected with laser-captured microscopy from the tumour and adjacent normal and dysplastic epithelium. DNA was extracted, and exons 5,9 of the TP53 gene were amplified by PCR. Amplified products were separated by denatured gradient gel electrophoresis. Fragments with a deviant DGEE pattern were sequenced. Results:,TP53 mutations were found in six of 18 tumours. Fourteen specimens contained histologically normal mucosa adjacent to the tumour; 13 of these showed small clusters of p53 positive cells. Seven specimens contained both histological normal and dysplastic epithelial tissues adjacent to the tumour. A TP53 mutation was found in only one specimen; this mutation appeared in the normal mucosa, the adjacent tumour, and the epithelial dysplasia. Conclusion:, We found that upregulation of p53 was a frequent event in histological normal mucosa adjacent to OSCC; however, it was rarely associated with a mutation in the TP53 gene. [source] Computer-assisted morphometric analysis of lymphatic vessel changes in hamster tongue carcinogenesisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 7 2010Dong Chen J Oral Pathol Med (2010) 39: 518,524 Background:, To characterize lymphangiogenesis in early-stage hamster tongue carcinoma development, morphological features and spatial relationships of lymphatic vessels. Methods:, Lymphatic vessels were examined histochemically, using 5,-Nase-ALPase enzyme and combined light and electron microscopy to measure lymphatic vessel area (LVA) and lymphatic vessel density (LVD). Results:, In atypical hyperplastic tissues, LVA was found to be 1429.97 and LVD was found to be 39, in carcinoma in situ LVA was 2538.33 and LVD was 48, and in micro-invasive carcinoma LVA was 5733.74 and LVD was 59. Increased lymphangiogenesis was seen in pre-neoplastic states and in early-stage oral squamous cell carcinoma (OSCC). Small regular lymphatic vessels predominated in atypical hyperplasia, and large, irregular lymphatic vessels in early-stage OSCC. Lymphatic endothelial vessels were stretched and porous over large areas. Conclusions:, Newly formed lymphatics and patulous intercellular junctions may be optimally suited for tumor cell metastasis through lymphatic channels in early- and middle-phase carcinogenesis. Lymphatic capillary LVA and LVD became enlarged, and positively correlated, with malignancy, but show no correlation with 7,12-dimethylbenz[a]anthracene-induced time. [source] Evaluation of survivin as a prognostic marker in oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2010Yong-Hun Kim J Oral Pathol Med (2010) 39: 368,375 Background:, Poor prognosis of oral squamous cell carcinoma (OSCC) is partly attributed to the lack of significant tumor marker for accurate staging and prognostication. We have evaluated survivin, which is a member of the inhibitor of apoptosis family as a cancer marker associated with proliferation, angiogenesis, oral carcinogenesis, and OSCC patient survival, as we reported a prognostic significance of survivin expression in lymph node previously. Methods:, To evaluate survivin expression in six OSCC cell lines, Western blotting was performed. Hamster oral carcinogenesis model was used to observe changes of survivin expression in oral carcinogenesis. Finally, we assessed the diagnostic and prognostic significance of survivin in a series of 38 primary OSCC through immunohistochemistry (CD31, PCNA) and Kaplan,Meier's test. Results:, Survivin expression was detected in all OSCC cell lines at a varying level but not observed in normal gingival keratinocyte cells. In hamster model, survivin expression was observed from 8 weeks through 16 weeks and the intensity of expression became strong until 16 weeks. Clinicopathological analysis revealed a significant correlation between survivin expression and lymph node metastasis (P = 0.006) and proliferation (P < 0.001). However, there was no significant relationship with differentiation, micro vessel density, and cancer stage based on TNM. Survivin overexpression had a significant negative effect on survival of patients. Conclusions:, These results demonstrate the significant relationship between survivin expression and oral carcinogenesis and aggressiveness of OSCC including survival rate of patient. Survivin therefore may be used as a significant cancer marker to gain prognostic information of OSCC. [source] Stromal laminin chain distribution in normal, hyperplastic and malignant oral mucosa: relation to myofibroblast occurrence and vessel formationJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2010Marcus Franz J Oral Pathol Med (2010) 39: 290,298 Background:, The contribution of stromal laminin chain expression to malignant potential, tumour stroma reorganization and vessel formation in oral squamous cell carcinoma (OSCC) is not fully understood. Therefore, the expression of the laminin chains ,2, ,3, ,4, ,5 and ,2 in the stromal compartment/vascular structures in OSCC was analysed. Methods:, Frozen tissue of OSCC (9× G1, 24× G2, 8× G3) and normal (2×)/hyperplastic (11×) oral mucosa was subjected to laminin chain and ,-smooth muscle actin (ASMA) immunohistochemistry. Results were correlated to tumour grade. The relation of laminin chain positive vessels to total vessel number was assessed by immunofluorescence double labelling with CD31. Results:, Stromal laminin ,2 chain significantly decreases and ,3, ,4, ,5 and ,2 chains and also ASMA significantly increase with rising grade. The amount of stromal ,3, ,4 and ,2 chains significantly increased with rising ASMA positivity. There is a significant decrease in ,3 chain positive vessels with neoplastic transformation. Conclusions:, Mediated by myofibroblasts, OSCC development is associated with a stromal up-regulation of laminin isoforms possibly contributing to a migration promoting microenvironment. A vascular basement membrane reorganization concerning ,3 and ,2 chain laminins during tumour angioneogenesis is suggested. [source] Decreased expression of Ep-CAM protein is significantly associated with the progression and prognosis of oral squamous cell carcinomas in TaiwanJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2009Emily Ya-Chi Hwang Background:, The epithelial cell adhesion molecule (Ep-CAM) is involved in cell signaling, migration, proliferation, cell-cycle regulation, and cancer metastasis. Methods:, This study used an immunohistochemical technique to examine the expression of Ep-CAM protein in 84 specimens of oral squamous cell carcinoma (OSCC), 98 specimens of oral epithelial dysplasia (OED, 31 mild, 41 moderate, and 26 severe OED cases), and 15 specimens of normal oral mucosa (NOM). Results:, We found that the mean Ep-CAM labeling indices (LIs) decreased significantly from NOM (80 ± 18%) and mild OED (76 ± 14%) through moderate OED (66 ± 22%) and severe OED (55 ± 20%) to OSCC samples (46 ± 16%, P < 0.001). A significant correlation was found between the lower mean Ep-CAM LI and OSCCs with larger tumor size (P = 0.003), positive lymph node metastasis (P = 0.022), more advanced clinical stages (P < 0.001), cancer recurrence (P = 0.021), or extracapsular spread of lymph node (P = 0.015). However, only Ep-CAM LI < 50% (P < 0.0001) was identified as an independent unfavorable prognosis factor by multivariate analyses with Cox proportional hazard regression model. Kaplan,Meier curve showed that OSCC patients with an Ep-CAM LI < 50% had a significantly poorer cumulative survival than those with an Ep-CAM LI , 50% (P < 0.00001, log-rank test). Conclusions:, We conclude that the decreased expression of Ep-CAM protein is an early event in oral carcinogenesis. The Ep-CAM LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients. [source] RNA from brush oral cytology to measure squamous cell carcinoma gene expressionJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 2 2008Joel L. Schwartz Background:, RNA expression analysis of oral keratinocytes can be used to detect early stages of disease such as oral cancer or to monitor on-going treatment responses of the same or other oral diseases. A limitation is the inability to obtain high quality RNA from oral tissue without using biopsies. While oral cytology cell samples can be obtained from patients in a minimally invasive manner they have not been validated for quantitative analysis of RNA expression. Methods:, As a starting point in the analysis of tumor markers in oral squamous cell carcinoma (OSCC), we examined RNA in brush cytology samples from hamsters treated with dibenzo[a,l]pyrene to induce oral carcinoma. Three separate samples from each animal were assessed for expression of candidate marker genes and control genes measured with real-time RT-PCR. Results:, Brush oral cytology samples from normal mucosa were shown to consist almost exclusively of epithelial cells. Remarkably, ß-2 microglobulin and cytochrome p450, 1B1 (CYP1B1) RNA showed potential utility as markers of OSCC in samples obtained in this rapid and non-surgical manner. Conclusion:, Brush oral cytology may prove useful as a source of RNA for gene expression analysis during the progression of diseases of the oral epithelium such as OSCC. [source] Frequent high telomerase reverse transcriptase expression in primary oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2007Kolja Freier Background:, Gene copy number gain of chromosomal arm 5p is frequently found in oral squamous cell carcinoma (OSCC) suggesting the activation of proto-oncogenes. TERT is a candidate gene encoding for human telomerase reverse transcriptase (hTERT). The aim of the present study was to elucidate the relevance of TERT copy number gain and high hTERT expression in OSCC. Methods:, Fluorescence in situ hybridization (FISH) for TERT and immunohistochemistry (IHC) for hTERT were performed to analyze TERT copy numbers and hTERT expression, respectively, on tissue microarray (TMA) sections including n = 247 OSCC and n = 105 pharyngeal and laryngeal squamous cell carcinomas (PSCC/LSCC). Results:, Increased hTERT protein expression was more frequently found in OSCC (71.1%, 155/218) than in PSCC/LSCC (36.0%, 35/89) (P < 0.001). By contrast, specific TERT amplifications were less common in OSCC (2.1%, 4/191) compared with PSCC/LSCC (9.9%, 8/81) (P = 0.047). Conclusions:, High hTERT expression is a frequent finding in OSCC. It might be a promising target for the development of specific anti-neoplastic therapy approaches. [source] A quantitative co-localization analysis of large unspliced tenascin-CL and laminin-5/,2-chain in basement membranes of oral squamous cell carcinoma by confocal laser scanning microscopyJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2007Marcus Franz Background:, A structural interaction of the oncofetal large tenascin-C splice variants (Tn-CL) and the ,2-chain of laminin-5 (Ln-5/,2) was recently demonstrated in oral squamous cell carcinoma (OSCC). In situ different patterns of co-localization and co-deposition of both proteins could be detected. Especially the co-localization in re-established basement membrane (BM) structures seemed to be biologically meaningful within the process of tumour progression. Methods:, The amount of Tn-CL incorporated in reorganized OSCC BM structures at the tumour margins was investigated by a laser scanning microscopy-based quantitative co-localization analysis. Results:, In the BM of normal oral mucosa no Tn-CL could be detected. In dysplastic and neoplastic oral mucosa a distinct co-localization of Tn-CL and Ln-5/,2 in the BM region could be observed. The extent of Tn-CL arrangement into reorganized BM structures correlated with malignancy grade. Conclusions:, The results suggest at first, a modulation of carcinomatous BM structures by the inclusion of oncofetal matrix proteins during tumour progression and secondly, the BM incorporation of the adhesion-modulating molecule Tn-CL as a pre-invasive structural phenomenon in OSCC. [source] Differential expression of E-cadherin in metastatic lesionscomparing to primary oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 10 2006K.-F. Hung Background:, The main cause of treatment failure in resectable oral squamous cell carcinoma (OSCC) is metastasis. E-cadherin (E-cad) plays a principal role in cell adhesion and motility, and is associated with OSCC progression. The aim of this study was to investigate the clinical significance of E-cad expression in OSCC with lymph node metastasis which had radical neck dissection done. Method:, Immunohistochemistry was used to detect E-cad expression in normal oral mucosa (NOM) (n = 10), oral precancerous lesions (OPLs) (n = 20), primary OSCC (n = 45), and their paired metastatic lesions (n = 45). E-cad immunoreactivity correlated with the clinicopathologic features. Results:, E-cadherin immunoreactivity was progressively reduced in the NOM followed by OPLs and primary OSCC (58%). It decreased significantly in the advanced stages of OSCC. However, the increase in E-cad immunoreactivity was observed in the majority (60%) of metastatic lesions in relation to primary OSCC. Patients with such increased or positive immunoreactivity of E-cad in metastatic lesions exhibited worse prognosis. Conclusion:, The findings suggested a dynamic change in E-cad immunoreactivity during tumorigenesis and metastasis of OSCC. In a multivariate analysis, E-cad immunoreactivity in metastasis lesions (odds ratio 3.74, 95% CI 1.15,14.67; P = 0.040) implied the potential role of mortality predictors for OSCC cases with nodal involvement. [source] Increased survivin expression in high-grade oral squamous cell carcinoma: a study in Indian tobacco chewersJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 10 2006C. Jane Background:, Oral cancer is one of the five leading sites of cancer in the Indian population. In the present study we analyzed the expression of apoptosis regulating genes, viz. survivin, Bcl-2, Bax and p53 in precancerous and cancerous lesions of the buccal mucosa of Indian tobacco chewers. Method:, Paraffin-embedded tissue samples from 38 patients with primary oral squamous cell carcinoma (OSCC) and 17 patients with leukoplakia were used. The expression of survivin, Bcl-2, Bax, and p53 was evaluated using immunohistochemical staining method. Results:, Thirty-six percent OSCC were found to be positive for nuclear p53 staining while none of the precancerous lesions showed p53 positivity. Survivin, Bcl-2 and Bax expression was found to increase with increased grade of malignancy. Increase in survivin expression was statistically most significant (P < 0.001). Conclusion:, Increased expression of anti-apoptotic survivin in high-grade tumors suggests that survivin is likely to contribute significantly to apoptosis resistance in response to therapy. [source] Correlation of basic fibroblast growth factor expression with the invasion and the prognosis of oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2006Takashi Hase Background:, The aim of this study was to evaluate the relationship between the expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in cancer cells and fibroblasts at the invasive front of oral squamous cell carcinoma (OSCC), and the pathologic and clinical characteristics. Methods:, Sections of 61 biopsy specimens of primary OSCC were immunostained to assess the expression of bFGF and FGFR-1 in cancer cells and fibroblasts at the invasive front. Results:, The bFGF and FGFR-1 expressions in the cancer cells were evident in all specimens, whilst, in fibroblasts, they were detected in 41 (67%) of 61 specimens. These expressions in the fibroblasts occurred notably more often in high-invasive OSCC specimens than low-invasive OSCC specimens. The prevalence of bFGF and FGFR-1 expressions in cases with lymph node metastasis was significantly higher (P < 0.05) than in cases without metastasis. Moreover, these expressions were well correlated with patient prognosis. Conclusion:, This study concludes that bFGF and FGFR-1 expressions in fibroblasts at the invasive front are linked to the mode of invasion and the prognosis in OSCC. [source] Gene,environment interaction involved in oral carcinogenesis: molecular epidemiological study for metabolic and DNA repair gene polymorphismsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2006Tomotaka Sugimura Background:, Exposure to environmental carcinogens leads to oral squamous cell carcinoma (OSCC); however, the impact of genetic variations in carcinogen metabolisms and DNA repair on OSCC risk considering environmental exposures has not been clearly elucidated. Methods:, We conducted a case,control study with 122 cases and 241 controls. The risk of OSCC was evaluated in 10 genetic polymorphisms of nine genes, such as CYP1A1, CYP2E1, GSTM1, GSTT1, XPA, XPC, XPC, XPF and ERCC1. Gene,environment interaction was also evaluated. Results:, We found that CYP2E1 and XPA polymorphisms significantly affected the OSCC risk. Gene,environment interactions with smoking were significant for CYP2E1 and ERCC1 polymorphisms. Odds ratios for gene,environment interaction were 7.98 (P = 0.036), 9.67 (P = 0.017) and 8.49 (P = 0.031) for CYP2E1RsaI, DraI and ERCC1 polymorphisms, respectively. No interaction was observed with heavy drinking and any polymorphisms. Conclusion:,CYP2E1, XPA and ERCC1 polymorphisms may affect the risk of OSCC. [source] The expression of NMDA receptor 1 is associated with clinicopathological parameters and prognosis in the oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2004S.-W. Choi Background:, Glutamate activates the N -methyl- d -aspartate (NMDA) receptors and this receptor is involved in the proliferation and migration of various tumour cells in vitro. However, the relationship between NMDA receptor expression and clinical parameters in cancer patients is unclear. Therefore, NMDA receptor 1 (NMDAR1) expression along with its clinical significance was examined in patients with oral squamous cell carcinoma (OSCC). Methods:, Eighty-one tumour specimens from OSCC patients were used to determine the NMDAR1 expression level by immunohistochemical staining. The control was obtained from a matched normal adjacent mucosa. The cases were considered to be positive if reactivity was displayed in >25% of the cells. Results:, The NMDAR1 reactivity was positive in 50 of 81 cases, while it was negative in the control. NMDAR1 expression was significantly associated with a lymph node metastasis (P = 0.008), the tumour size (P < 0.001), and the cancer stage (P = 0.034). The patients whose tumours expressed NMDAR1 had a significantly poorer survival than the patients who were NMDAR1-negative (log-rank = 6.45, d.f. = 1, P = 0.011). Conclusions:, The NMDAR1 overexpression was significantly associated with the prognosis-related factors. Therefore, it might be one of the prognostic markers of OSCC. [source] Correlation between functional genotypes in the matrix metalloproteinases-1 promoter and risk of oral squamous cell carcinomasJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 6 2004Shu-Chun Lin Background:, Oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF), which are highly associated with areca use, are prevalent in most Asian countries. Matrix metalloproteinases (MMPs) are superfamily of metal-dependent proteolytic enzymes, mediating the degradation of extracellular matrix. Insertion/deletion (,1607 2G,1G) polymorphism has been described in the promoter region of the human matrix metalloproteinases-1 (MMP-1) genes, which cause an alteration in the transcriptional activity. This genotype is associated with risks of cancer genesis and metastasis. In this paper, we studied the relationship between such genotype and areca-associated oral diseases. Methods:, Genomic DNA from the blood of OSCC (n = 121), OSF (n = 58) cases and controls (n = 147) were amplified by polymerase chain reaction (PCR)-based genotyping. The OSCC were further grouped into buccal squamous cell carcinoma (BSCC) and non-buccal suqmaous cell carcinoma (NBSCC), in accord with the site of involvement. The significance of the differences was assessed by Fisher's exact test. Results:, The 2G genotype in MMP-1 promoter was observed with a higher frequency in both OSCC (0.69, P = 0.06) and NBSCC (0.76, P = 0.03) cases compared with controls (0.63), with an odds ratio of 2.17 and 4.58, respectively. This genotype was not related to the risk of OSF. No other clinicopathologic parameter was associated with the genotypes in OSCC cases. Conclusion:, The results showed that 2G genotype in MMP-1 promoter was associated with the risk of OSCC. [source] Growth of malignant oral epithelial stem cells after seeding into organotypical cultures of normal mucosaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 2 2004Ian C. Mackenzie Background:, Oral squamous cell carcinoma (OSCC) is associated both with the local expansion of clones of malignant cells and with their further migration to regional and distant sites. The interactions that occur between normal and malignant cells during these events are not well modelled by standard culture conditions, but organotypical cultures, in which epithelial cells are grown on a matrix containing fibroblasts, provide a suitable environment for such investigations. Methods:, Cells from five cell lines, each derived from OSCC and marked by retroviral transduction with alkaline phosphatase, were incorporated as small subpopulations (0.1,5%) in uniformly differentiating organotypical cultures constructed from normal oral mucosal cells. The patterns of growth of the malignant cells within the normal epithelium were examined for 3 weeks. Results:, There was variation between the different cell lines in their rates and patterns of growth, but all cell lines produced clusters of malignant cells that had expanded within 3 weeks to replace the normal epithelium. The appearance and spacing of these clusters suggested that each was derived from a single progenitor cell. The number of malignant cells initially present within a given area of organotypical epithelium was much greater than the number of expanding cell clusters subsequently formed. Cluster-forming cells thus represented only a subpopulation of the tumour cells. Conclusions:, The organotypical model allows examination of interactions occurring between cells derived from OSCC and normal epithelia. The three-dimensional nature of organotypical cultures, together with their more normal patterns of differentiation, provides an environment that more closely mimics the in vivo environment in which tumours develop. The finding that only a subpopulation of tumour cells forms expanding tumour colonies suggests a range of growth potentials within a tumour population and may provide preliminary evidence for some form of stem and amplifying cell pattern. [source] Establishment of OC3 oral carcinoma cell line and identification of NF-,B activation responses to areca nut extractJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 2 2004Shu-Chun Lin Background:, Cell lines derived from oral squamous cell carcinoma (OSCC) exposed to variable etiological factors can bestow advantages in understanding the molecular and cellular alterations pertaining to environmental impacts. Most OSCC cell lines have been established from smoker patients or areca chewing/smoker patients, carrying the genomic alterations in p53. Methods:, A new cell line, oral carcinoma 3 (OC3), was established from an OSCC in a long-term areca (betel) chewer who does not smoke. Cellular and molecular features of OC3 were determined by variable assays. Results:, The cultured monolayer cells were mainly polygonal and had the expression of cytokeratin 14. The chromosomal analysis using comparative genomic hybridization has revealed the gain in chromosomes 1q, 5q, and 8q, the loss in 4q, 6p, and 8p as well as the gain of entire chromosome 20. Loss of heterozygosity and instability in multiple microsatellite markers in chromosome 4q were also noted. OC3 cells bear wild-type p53 coding sequence and have a high level of p53 expression. Its p21 expression was similar to that in normal human oral keratinocyte (NHOK). Interestingly, activation of nuclear factor ,B (NF-,B) in OC3 cells following the treatment of areca nut extract was observed. Conclusion:, OC3 cell line could be valuable in understanding the genetic impairments and phenotypic changes associated with areca in oral keratinocyte. [source] Cyclic guanosine monophosphate phosphodiesterase activity in human gingival carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2003Giuseppe Spoto Abstract Background:, Cyclic guanosine monophosphate (cGMP) is an essential second messenger metabolized by phosphodiesterases (PDEs). Objectives:, We looked for a possible correlation of PDE activities in human oral squamous cell carcinoma (OSCC) with and without lymph node metastases. Materials and methods:, The analysis of phosphodiesterase activity and the cGMP assay were done by reverse-phase HPLC on samples of fresh or frozen gingival tissues. Analysis of cGMP was confirmed with the enzyme-linked immunoabsorption assay. Results and conclusions:, cGMP PDE activity was 34.92 ± 7.17 SD, 12.89 ± 4.43 SD, and 35.88 ± 8.76 SD (nmols/mg of protein), respectively, in controls, samples without lymph node involvement (N,), and specimens with lymph node metastases (N+). cGMP values were 1.97 ± 0.63 SD, 3.30 ± 1.47 SD, and 3.49 ± 1.47 SD (nmols/mg of protein). Our data support the hypothesis of a role for cGMP and PDE in the progression of OSCC. [source] Invasive front grading: reliability and usefulness in the management of oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2003Faleh A. Sawair Abstract Background:, The value of histological grading was examined with emphasis on reliability of assessment in 102 cases of intraoral squamous cell carcinoma from Northern Ireland with known outcome. Methods:, Two pathologists independently graded the invasive tumour front blinded to the stage and outcome. Results:, Intraobserver agreement was acceptable but interobserver agreement was not satisfactory. The degree of keratinisation was assessed most consistently while nuclear polymorphism was the least reliable feature. Multivariate survival analysis showed that the total grading score was associated with overall survival while the pattern of tumour invasion was the most valuable feature in estimating regional lymph node involvement. The number of positive lymph nodes was strongly associated with regional relapse, while the treatment modality and status of the surgical margins correlated with local relapse. Conclusions:, Grading of selected features in OSCC is reliable and can facilitate treatment planning. [source] Genetic polymorphism of cytochrome P4501A1 and susceptibility to oral squamous cell carcinoma and oral precancer lesions associated with smoking/betel useJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2002Shou-Yen Kao Abstract Background:,, The importance of the CYP1A1 polymorphisms at exon 7 (Ile/Val) and 3,-untranslated region (3,-UTR) has been controversial in oral squamous cell carcinoma (OSCC) or head and neck SCC (HNSCC) denoting the value of exploring the correlation between these polymorphisms and risk of betel/smoking associated OSCC. It is also important to evaluate the association between CYP1A1 polymorphisms and susceptibility of oral precancerous lesion (OPL) to confirm the findings in OSCC cases. Methods:,, We examined polymorphic prevalence of CYP1A1 at exon 7 (Ile/Val) and 3,-UTR in 106 cases with OSCC, 60 cases with OPL, and 146 controls. DNA isolated from surgical specimens and whole blood was used for PCR-based genotyping. Results:,, The prevalence of the CYP1A1 A/G genotype (Ile/Val) and G/G genotype (Val/Val) in exon 7 of cases with OSCC (79.2 and 7.6%) and OPL (68.3 and 10%) were significantly higher than in controls (53.4 and 1.4%) (P < 0.0001). The novelty of the present study is that we identified the onset age of OSCC in CYP1A1 A/G genotype to be significantly younger than that in A/A genotype (P < 0.01). No significant difference was seen between cases and controls regarding the polymorphisms at 3,-UTR. Conclusion:,, The findings indicate that the individuals with the CYP1A1 exon 7 containing G allele were at increased risk for OSCC and OPL. [source] Immunohistochemical evidence of PTEN in oral squamous cell carcinoma and its correlation with the histological malignancy grading systemJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 7 2002Cristiane Helena Squarize Abstract PTEN is a tumor suppressor gene that encodes a dual phosphatase protein capable of modulating membrane receptors and interaction of the cell and extracellular stimuli. PTEN regulates cell physiology such as division, differentiation/apoptosis and also migration and adhesion. The expression of PTEN was evaluated by immunohistochemistry in OSCC and compared to a well-established histological malignancy grading system. The well-differentiated OSCC were 59.1% and poorly differentiated were 40.9%. According to PTEN expression, the cases were 45.5% positive (the entire tumor showed stained), 22.7% mixed (both negative and positive cells were present) and 31.8% negative (no staining was seen in the tumor cells). PTEN expression in OSCC was related to the malignancy grade (P < 0.0005). Aggressive tumors with a high score of malignancy did not express PTEN, and clearly, the PTEN expression was present in the epithelium adjacent to the tumor. Negative cells were in the invasion border of the tumor. This result suggests that PTEN is related to histologic pattern and biological behavior of OSCC and may be a used as a prognostic marker in the future. The role of PTEN during carcinogenesis and as a biomarker should be further investigated. [source] | ||||||||||||||||||||||