The MN protein is a newly described biomarker found to be overexpressed in most cervical carcinomas. This study was an effort to evaluate the prognostic importance of tumor MN expression, HPV status, and the presence of other biomarkers in cervical cancers. Tumor DNA and protein for study were extracted from archived frozen tissue. Tumor tissues and controls were evaluated by Western blot analysis for MN, intestinal alkaline phosphatase (IAP), c-myc, and p53 protein overexpression. Immunohistochemistry was performed for MN quantification and the study of expression patterns in histologic subtypes of cervical cancer. HPV data were obtained by PCR amplification of extracted DNA using consensus and type-specific primers. Clinical data were obtained from the patients' records and from the cancer registry. Clinical and molecular data were correlated by chi2, Fisher's exact test, and logistic regression. The results demonstrate that IAP is not overexpressed in clinical specimens of cervical carcinoma, although in somatic cell hybrid experiments, overexpression of IAP correlates with the malignant state. None of 47 tumors, including those which were HPV negative, overexpressed p53. c-myc protein overexpression occurred in 11 of 52 tumors, most of which contained HPV 16, but this was not significantly different from the tumors as a whole. There was no apparent association between MN protein expression and the overexpression of c-myc protein. MN was overexpressed in all cancers and quantitatively varied with the histologic subtype. Specifically, lower expression of MN correlated with adenosquamous 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 associated with deeper cervical stromal invasion (P < 0.03). Further, low expression of MN correlated with lymph node metastases in small (<3.5 cm) IB and IIA cervical cancers (P < 0.04). These data suggest that MN is emerging as a potentially important new biomarker for cervical carcinoma. The overexpression commonly seen in cervical cancer is possibly associated with loss of a critical tumor suppressor gene located on chromosome 11. Low expression of MN antigen appears to correlate with several adverse prognostic features and further prospective study is warranted.