Expression and mutational analysis of P53 in stage IB and IIA cervical cancers.

Abstract

This study evaluates overexpression of the p53 protein and point mutation in the P53 gene in a group of patients with stage IB and IIA cervical cancer. We reviewed the medical records of all patients who underwent radical hysterectomy for the treatment of stage IB and IIA cervical cancer between 1980 and 1985 at Memorial Sloan-Kettering Cancer Center. Overexpression of p53 protein was determined with the use of immunohistochemistry on fixed and paraffin-embedded tissue. Two blocks were selected for each tumor, and tissue sections from each block were tested with both monoclonal (Ab-6) and polyclonal (CM-1) anti-p53 antibodies. Molecular analysis for determination of specific P53 gene mutations was performed with single-strand conformation polymorphism analysis. A group of 132 patients was identified for inclusion in the study. Fifty-eight of 132 tumors (44%) showed overexpression of the p53 protein and were subjected to molecular analysis. Discrepancy between pairs of blocks (7/132, 5.3%) and between antibodies for the same block (5/264, 1.9%) was uncommon. High-level overexpression was rare (5/132, 3.8%). No difference in survival was found on the basis of overexpression of p53 protein. Only one of the 58 cases (1/58, 1.7%) that showed overexpression of the p53 protein exhibited a point mutation (exon 8) in P53 by single-strand conformation polymorphism. This case had a low level of overexpression of p53 protein on immunohistochemistry. Low levels of overexpression of p53 were frequently seen in early cervical cancers (40/132, 30%). However, mutation of the P53 gene was rarely seen in these tumors. Overexpression of p53 protein as detected by immunohistochemistry is not predictive of a somatic mutation in the P53 gene in cervical cancer. Molecular analysis is required for confirmation of P53 mutations in these tumors.