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

Abstract

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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. (Am J Obstet Gynecol 1996;175:1266-71.)