EXPRESSION AND MUTATIONAL ANALYSIS OF P53 IN STAGE IB AND IIA CERVICAL CANCERS

OBJECTIVE: This study evaluates overexpression of the p53 protein and point mutation in the P53 gene in a group of patients with stage IB an d IIA cervical cancer. STUDY DESIGN: We reviewed the medical records o f all patients who underwent radical hysterectomy for the treatment of stage IB and IIA cervical cancer between 1980 and 1985 at Memorial Sl oan-Kettering Cancer Center. Overexpression of p53 protein was determi ned with the use of immunohistochemistry on fixed and paraffin-embedde d tissue. Two blocks were selected for each tumor, and tissue sections from each block were tested with both monoclonal (Ab-6) and polyclona l (CM-1) anti-p53 antibodies. Molecular analysis for determination of specific P53 gene mutations was performed with single-strand conformat ion polymorphism analysis. A group of 132 patients was identified for inclusion in the study. RESULTS: Fifty-eight of 132 tumors (44%) showe d overexpression of the p53 protein and were subjected to molecular an alysis. Discrepancy between pairs of blocks (7/132, 5.3%) and between antibodies for the same block (5/264, 1.9%) was uncommon. High-level o verexpression was rare (5/132, 3.8%). No difference in survival was fo und 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 exhib ited a point mutation (exon 8) in P53 by single-strand conformation po lymorphism. This case had a low level of overexpression of p53 protein on immunohistochemistry. CONCLUSIONS: Low levels of overexpression of p53 were frequently seen in early cervical cancers (40/132, 30%). How ever, mutation of the P53 gene was rarely seen in these tumors. Overex pression of p53 protein as detected by immunohistochemistry is not pre dictive of a somatic mutation in the P53 gene in cervical cancer. Mole cular analysis is required for confirmation of P53 mutations in these tumors.