Markers Implicating Early Malignant Events in B & P vical Carcinogenesis -

ownloade kground: Human papillomavirus can induce a stepwise progression of precursor lesions to carcinoma. ive and specific molecular markers are needed to identify the cervical lesions (CIN) at risk for this ssion. hTERT activation could be one indicator of a point of no return in malignant progression. thods: The UT-DEC-1 cell line is an in vitro model for the study of human papillomavirus–induced ssion. Using molecular mining, nine potential genes interlinking hTERT and viral oncogene expression he phenotypical features of CIN2 were identified. After preliminary testing with real-time PCR, five were selected for further analysis: hTERT, DKC1, Bcl-2, S100A8, and S100A9. These proteins were also in a series of 120 CIN lesions using immunohistochemistry. ults: Analysis of the mRNA expression of these genes at different cell passages revealed three time with significant changes. hTERT, Bcl-2, and S100A9 were also overexpressed in CIN lesions, and the sion pattern changed during the progression toward CIN3 lesions. clusions: These identified time points that were combined with the mRNA overexpression of target matched events previously shown to be important in the progression toward malignancy: (a) the viral ation into the cell genome and episome loss; (b) the selection of cells with an acquired growth advantage ility to maintain telomerase activity; and (c) the final stage of malignancy with permanently upreguelomerase. act: hTERT, Bcl-2, and S100A9 together might compose a potential prognostic marker panel for the Imp assessment of CIN lesions. These results, however, need further validation in prospective clinical settings. Cancer Epidemiol Biomarkers Prev; 19(8); 2003–12. ©2010 AACR.