Viral and histopathologic correlates of MN and MIB-1 expression in cervical intraepithelial neoplasia

A recently studied tumor antigen, MN, has been associated with cervical carcinomas and cervical intraepithelial neoplasms (CIN), suggesting that it may serve as a marker for cervical cancer or cancer risk. To determine if expression of the MN antigen paralleled parameters reflecting viral or biological events in precursor epithelium, MN expression was correlated with MIB-1 expression, morphological phenotype, and human papillomavirus (HPV) distribution and type in a series of CINs. Seventy-three percent, 62% and 83% of CIN I, II, and III, respectively, were MN antigen positive. The proportion of neoplastic cells immunoreactive for MN did not correlate with the CIN grade or with HPV types stratified by their association with cancer. Evaluation of serial sections showed no correlation between the frequency of MN antigen staining, the proportion of MIB-1 immunoreactive cells, or the proportion of HPV positive cells detected by in situ hybridization (ISH). CINs associated with prototypical high risk (HPV 16) types exhibited increased immunostaining for the MIB-1 antigen and were more often classified as HSIL in contrast to the other types. Thus, although MN expression previously has been associated strongly with squamous carcinoma, it did not emerge as a specific marker for either cancer-associated HPV types or high grade CIN. CIN I lesions associated with low and high risk HPV types were not distinguished by MIB-1 expression and viral replication. This emphasizes the interrelationship between vegetative viral functions (including viral replication) and morphological phenotype, irrespective of HPV type.