A STUDY OF BIOMARKERS IN CERVICAL-CARCINOMA AND CLINICAL CORRELATION OF THE NOVEL BIOMARKER MN

The MN protein is a newly described biomarker found to be overexpresse d in most cervical carcinomas, This study was an effort to evaluate th e prognostic importance of tumor MN expression, HPV status, and the pr esence of other biomarkers in cervical cancers. Tumor DNA and protein for study were extracted from archived frozen tissue, Tumor tissues an d controls were evaluated by Western blot analysis for MN, intestinal alkaline phosphatase (IAP), c-myc, and p53 protein overexpression, Imm unohistochemistry was performed for MN quantification and the study of expression patterns in histologic subtypes of cervical cancer, HPV da ta were obtained by PCR amplification of extracted DNA using consensus and type-specific primers, Clinical data were obtained from the patie nts' records and from the cancer registry, Clinical and molecular data were correlated by chi(2), Fisher's exact test, and logistic regressi on. The results demonstrate that IAP is not overexpressed in clinical specimens of cervical carcinoma, although in somatic cell hybrid exper iments, overexpression of IAP correlates with the malignant state, Non e of 47 tumors, including those which were HPV negative, overexpressed p53. c-myc protein overexpression occurred in 11 of 52 tumors, most o f which contained HPV 16, but this was not significantly different fro m the tumors as a whole. There was no apparent association between MN protein expression and the overexpression of c-myc protein, MN was ove rexpressed in all cancers and quantitatively varied with the histologi c subtype, Specifically, lower expression of MN correlated with adenos quamous and less-differentiated histology (P <0.01 for grade 3 tumors) , Low expression of MN protein also correlated with HPV negativity (P <0.05). In stage IB and IIA cancers, low expression of MN was associat ed with deeper cervical stromal invasion (P <0.03). Further, low expre ssion of MN correlated with lymph node metastases in small (<3.5 cm) I B and IIA cervical cancers (P <0.04). These data suggest that MN is em erging as a potentially important new biomarker for cervical carcinoma . The overexpression commonly seen in cervical cancer is possibly asso ciated with loss of a critical tumor suppressor gene located on chromo some 11. Low expression of MN antigen appears to correlate with severa l adverse prognostic features and further prospective study is warrant ed. (C) 1996 Academic Press, Inc.