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Oral Carcinogenesis (oral + carcinogenesi)
Selected AbstractsRecurrent 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] Human telomerase catalytic subunit gene re-expression is an early event in oral carcinogenesisHISTOPATHOLOGY, Issue 1 2004B Luzar Aims:, Detection of telomerase catalytic subunit (hTERT) mRNA has been used as a surrogate marker for estimation of telomerase activity. The exact role and timing of telomerase re-activation, a key enzyme implicated in cellular immortalization and transformation, in the multistep process of oral carcinogenesis is still unknown. The aim was to test the hypothesis that (i) quantitative rather than qualitative differences exist in the level of hTERT mRNA expression between normal oral mucosa, different grades of oral epithelial abnormalities and squamous cell carcinomas of the oral cavity, and that (ii) hTERT gene re-expression is an important, probably early event in oral carcinogenesis. Methods and results: The relative quantity of hTERT mRNA was analysed in 45 frozen oral epithelia representing different morphological stages of oral carcinogenesis classified according to the Ljubljana classification and in 37 oral squamous cell carcinomas, using a commercially available LightCycler Telo TAGGG hTERT Quantification kit. hTERT mRNA was not detected in normal or reactive hyperplastic oral epithelia, but was present in 43% of atypical hyperplasias (premalignant lesions), 60% of intraepithelial carcinomas and 68% of oral squamous cell carcinomas. Statistical analysis revealed two groups of oral epithelial changes, with significant differences in the levels of hTERT mRNA expression: 1, normal and reactive hyperplastic oral epithelium, and 2, atypical hyperplasia, intraepithelial carcinomas and squamous cell carcinomas. Conclusion:, These data suggest that hTERT gene re-expression represents an early event in the multistep process of oral carcinogenesis, already detectable at the stage of precancerous oral epithelial changes. Nevertheless, other genetic aberrations appear to be necessary for progression of oral epithelial abnormalities towards invasive squamous cell carcinoma. [source] Dual-mode reflectance and fluorescence near-video-rate confocal microscope for architectural, morphological and molecular imaging of tissueJOURNAL OF MICROSCOPY, Issue 1 2007ALICIA L. CARLSON Summary We have developed a near-video-rate dual-mode reflectance and fluorescence confocal microscope for the purpose of imaging ex vivo human specimens and in vivo animal models. The dual-mode confocal microscope (DCM) has light sources at 488, 664 and 784 nm, a frame rate of 15 frames per second, a maximum field of view of 300 × 250 ,m and a resolution limit of 0.31 ,m laterally and 1.37 ,m axially. The DCM can image tissue architecture and cellular morphology, as well as molecular properties of tissue, using reflective and fluorescent molecular-specific optical contrast agents. Images acquired with the DCM demonstrate that the system has the sub-cellular resolution needed to visualize the morphological and molecular changes associated with cancer progression and has the capability to image animal models of disease in vivo. In the hamster cheek pouch model of oral carcinogenesis, the DCM was used to image the epithelium and stroma of the cheek pouch; blood flow was visible and areas of dysplasia could be distinguished from normal epithelium using 6% acetic acid contrast. In human oral cavity tissue slices, DCM reflectance images showed an increase in the nuclear-to-cytoplasmic ratio and density of nuclei in neoplastic tissues as compared to normal tissue. After labelling tissue slices with fluorescent contrast agents targeting the epidermal growth factor receptor, an increase in epidermal growth factor receptor expression was detected in cancerous tissue as compared to normal tissue. The combination of reflectance and fluorescence imaging in a single system allowed imaging of two different parameters involved in neoplastic progression, providing information about both the morphological and molecular expression changes that occur with cancer progression. The dual-mode imaging capabilities of the DCM allow investigation of both morphological changes as well as molecular changes that occur in disease processes. Analyzing both factors simultaneously may be advantageous when trying to detect and diagnose disease. The DCM's high resolution and near-video-rate image acquisition and the growing inventory of molecular-specific contrast agents and disease-specific molecular markers holds significant promise for in vivo studies of disease processes such as carcinogenesis. [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] 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] 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] Loss of heterozygosity at APC and MCC genes of oral cancer and leukoplakia tissues from Indian tobacco chewersJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2003Nilabja Sikdar Abstract Background:, Loss of heterozygosity (LOH) at tumor suppressor genes, such as adenomatous polyposis coli (APC) and mutated in colon cancer (MCC) genes, is one of the early events in carcinogenesis of oral tissue in Caucasian and Chinese patients. We wanted to check whether it is also true in Indian oral pre-cancer and cancer patients. Methods:, Loss of heterozygosity at APC and MCC genes was investigated in 57 and 40 unrelated primary oral leukoplakia (a pre-cancerous lesion) and squamous cell carcinomas (SCC), respectively, by polymerase chain reaction. Results:, In these samples, most of the leukoplakia patients had tobacco smoking habit whereas majority of cancer patients had tobacco chewing habit. LOH at APC gene was observed in 4 of 16 (25%) and 1 of 29 (3%) informative tumor and leukoplakia DNAs from tobacco chewers, respectively. LOH at MCC gene was not detected either in tumor or in leukoplakia DNAs. Conclusion:, This infrequent LOH at APC gene of pre-cancer and cancer tissues suggests that it may not be an early event in oral carcinogenesis in these patients. [source] Human papillomavirus as a risk factor in oral carcinogenesis: a study using in situ hybridization with signal amplificationMOLECULAR ORAL MICROBIOLOGY, Issue 4 2008R. Acay Introduction:, It is still controversial whether human papillomavirus (HPV) can be considered a risk factor in oral carcinogenesis. The aim of this study was to detect HPV DNA in 50 cases diagnosed as oral leukoplakias, with different degrees of epithelial dysplasia, and as oral squamous cell carcinomas, using in situ hybridization with signal amplification (CSA-ISH). Methods:, HPV DNA was assessed in paraffin sections using CSA-ISH with a wide-spectrum biotinylated DNA probe. In HPV-positive cases, genotyping with specific probes to HPV types 6/11, 16/18 and 31/33 was performed. Results:, The overall prevalence of HPV infection was 24%, markedly higher than that found in the control group. Results showed a discrete proportional relationship in the indices found in leukoplakia with no dysplasia, leukoplakia with dysplasia, and squamous cell carcinoma, but this was not statistically significant. When separating the group of leukoplakia by degrees of dysplasia, this relation of proportion was not observed. In genotyping, HPV types 16/18 were the most prevalent, and types 6/11 were only found in groups of mild or no dysplasia. Conclusion:, The results suggest that HPV is not likely to play a role in the progression of malignant transformation in oral lesions. Nevertheless, the increased prevalence of HPV infection compared to normal oral mucosa and the fact that high-risk HPV types were the most frequently identified do not allow the exclusion of HPV as a risk factor in oral carcinogenesis. [source] Immunohistochemical demonstration of p63 in DMBA-induced hamster buccal pouch squamous cell carcinogenesisORAL DISEASES, Issue 5 2003YK Chen Objectives: Abnormalities in the p53 gene are regarded as the most consistent genetic abnormalities detected in head and neck squamous cell carcinogenesis. Two new members of the p53 gene family, p73 at the 1p36 region and p63 at the 3q27-29 region, have recently been identified. They share considerable sequence homology with p53 in the transactivation, DNA binding, and oligomerization domains, indicating possible involvement in carcinogenesis. To our knowledge, however, p63 expression in experimental oral carcinogenesis has not been studied. Materials and methods: Immunohistochemical analysis of p63 protein expression was performed in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch squamous cell carcinogenesis. Fifty outbred, young (6 weeks), male, Syrian golden hamsters (Mesocricatus auratus) were randomly divided into three experimental groups (each consisting of 10 3-, 9- and 15-week DMBA treated animals), and two control groups (with 10 animals in each). The pouches of the three experimental groups were painted bilaterally with a 0.5% DMBA solution three times a week. The treatment protocol for animals in one of the control groups was identical with only mineral oil applied, while the other control group remained untreated throughout the experiment. Results: In all of the untreated and mineral oil-treated pouch mucosa, nuclear positivity for p63 was mainly observed in the basal/parabasal cell layers. The p63 nuclear positivity extended from the basal/parabasal layers to the whole epithelial layers in the 3- and 9-week DMBA-treated pouch mucosa. Furthermore, the positive nuclear-stain cells were randomly distributed throughout the entire epithelial layers in the 3- and 9-week DMBA-treated pouch-mucosa specimens. In carcinomas from 15-week DMBA-treated pouch specimens, p63 staining was more uniform and homogeneous for the less-differentiated tumor areas. By contrast, p63 expression was noted mainly in the peripheral cells of tumor nests in the well-differentiated tumor areas. Conclusions: The results of this study are consistent with those from previous analyses of p63 expression in human oral mucosa, suggesting that p63 may be associated with the regulation of epithelial differentiation and proliferation in DMBA-induced hamster buccal pouch squamous cell carcinogenesis. Further study is required to investigate which p63 isoform(s) is/are involved in hamster buccal pouch carcinogenesis. [source] TNF-, Drives Matrix Metalloproteinase-9 in Squamous Oral Carcinogenesis,THE LARYNGOSCOPE, Issue 8 2008Laurie Hohberger MD Abstract Objectives/Hypothesis: It is well known that invasion is a seminal event in the progression of oral and other head and neck carcinoma sites. We have previously demonstrated tumor necrosis factor (TNF)-, and its dependent cytokines are upregulated in saliva during oral carcinogenesis. TNF-dependent events stimulate nuclear factor (NF)-,B and many NF-,B-dependent genes are associated with cancer progression. Materials and Methods: In the present study, we examined NF-,B stimulation of matrix metalloproteinase (MMP)-9 in a precancerous keratinocyte cell line that models leukoplakia (Rhek cells). We stimulated Rhek cells with both TNF-, and phorbol myristate acetate, known stimulants of NF-,B. We then assayed MMP-9 transcription and secretion by luciferase reporter genes, quantitative real-time polymerase chain reaction, and fluorometric enzyme-linked immunosorbent serologic assay. Results: We discovered that the MMP-9 promoter was significantly stimulated by phorbol myristate acetate and TNF-, on luciferase reporter gene assays. Further, we uncovered that functional MMP-9 promoter activation was accompanied by significant increases in MMP-9 gene expression, as judged by quantitative real-time polymerase chain reaction. Functional activation of the MMP-9 protein was stimulated by TNF-, and PMA on a fluorescent enzyme-linked immunosorbent serologic assay. Finally, we searched our salivary proteomic database for increases in MMP-9 and discovered it was the third most significant protein in salivas of oral cavity cancer patients over normal controls. Conclusions: We conclude the milieu cytokine, TNF-,, has the capacity to provide stimulation of events related to early invasion of oral cavity cancer, as judged by its ability to stimulate MMP-9. [source] The role of alcohol in oral carcinogenesis with particular reference to alcohol-containing mouthwashesAUSTRALIAN DENTAL JOURNAL, Issue 4 2008MJ McCullough Abstract Worldwide, oral cancer represents approximately 5 per cent of all malignant lesions, with over 800 new intra-oral squamous cell carcinomas registered in Australia each year. Despite recent advances in therapy, the five-year survival rate remains around 50 per cent and the sequelae of treatment can be seriously debilitating. It has been long established that smoking and alcohol consumption are risk factors linked to the development of oral cancer. This review assesses the epidemiological evidence, supportive in vitro studies and mechanism by which alcohol is involved in the development of oral cancer. Further, we review the literature that associates alcohol-containing mouthwashes and oral cancer. On the basis of this review, we believe that there is now sufficient evidence to accept the proposition that alcohol-containing mouthwashes contribute to the increased risk of development of oral cancer and further feel that it is inadvisable for oral healthcare professionals to recommend the long-term use of alcohol-containing mouthwashes. [source] | ||||||||||