Transformation Of Oral Lesions Research Articles

WNT signalling pathway in oral lesions.

Wingless-Integrated/Beta-catenin (WNT/-catenin) signalling pathway is one of the principal intercellular signalling pathways in humans. It plays an intrinsic role in the cellular proliferation, differentiation and regeneration along with many other cellular functions. Epigenetic deoxyribonucleic acid methylations and silencing of WNT signalling pathway genes have a significant role in malignant transformation of oral lesions such as oral submucous fibrosis, oral leukoplakia, oral lichen planus and erythroplakia. The increase in WNT inhibitory proteins along with inflammatory factors cause bone loss in periapical lesions, such as chronic apical periodontitis. This review discusses the molecular genetics of potentially malignant oral lesions, sheds light on our understanding of WNT/-catenin signalling in bone loss pertaining to periapical lesions, and alteration of this pathway for therapeutic benefits.

MicroRNA-375 as a biomarker for malignant transformation in oral lesions

Malignant transformation of oral premalignant lesions is the key process in the progression to oral squamous cell carcinoma (OSCC). Previously, we identified miR-7 and miR-21 as candidate oncogenes and miR-375 and miR-494 as candidate tumor suppressors in OSCC. We aim to evaluate these microRNAs as biomarkers of malignant transformation in oral premalignant lesions. Formalin-fixed, paraffin-embedded samples from progressive premalignant lesions and paired sequential OSCC tumors at the same site were obtained from same patients (n=31). Total RNA was extracted and analyzed for microRNA levels using real-time polymerase chain reaction. MiR-375 expression in progressive lesions was clearly lower than in nonprogressive control lesions (average eightfold difference, P=.0004). Furthermore, the expression of miR-375 decreased significantly after the progression from premalignant lesion to OSCC (P<.0001). Receiver operating characteristic curve analysis revealed that miR-375 was able to differentiate between progressive and nonprogressive premalignant lesions (P<.0001). MiR-375 downregulation in oral premalignant lesions is associated with a higher risk of malignant transformation.

Risk Estimation for a Malignant Transformation of Oral Lesions by S100A7 and Doc-1 Gene Expression

The objective of this study was the correlation of Doc-1- and S100A7-gene expression in common oral lesions with their cancerous-transformation risk. Biopsies (n = 15 each) of healthy gingiva, irritation fibromas, leukoplakias and Oral squamous cell carcinoma (OSCCs) were obtained, and after RNA-extraction, transcripts of Doc-1 and S100A7 were quantified by RT-PCR. In comparison with the healthy gingiva, the expression of Doc-1 was decreased, whereas the expression of S100A7 was upregulated in all lesions. As the extent of Doc-1-inactivation and S100A7-overexpression is correlated with their biological behavior, the combined investigation of both genes could be a promising marker in intraoral lesions to estimate the risk for their malignant transformation.

Human papillomavirus as a risk factor in oral carcinogenesis: a study using in situ hybridization with signal amplification

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). 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. 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. 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.