p53 mutation is infrequent in clear cell carcinoma of the ovary

Objective. p53 gene alteration has been extensively studied in epithelial o varian cancer. However, its occurrence in clear cell carcinoma, an infreque nt histologic subtype of epithelial ovarian cancer, is rarely reported. The aim of this study is to determine the status of p53 gene alteration in thi s distinct type of ovarian carcinoma. Methods. Paraffin blocks of tumors from 38 patients with primary or recurre nt ovarian clear cell carcinoma were studied for p53 alteration. All these tumors were subjected to immunohistochemical and molecular analysis. Two mo noclonal antibodies (DO-7 and PAb 1801) were used for immunohistochemical s taining, Genomic DNAs extracted from paraffin blocks of the 38 tumors were subscribed for a nested polymerase chain reaction/ single-strand conformati on polymorphism (PCR/SSCP) analysis. Tumors showing band shift on SSCP were further prepared for DNA sequencing to determine the site of mutation. Results. Overexpression of p53 was observed in only one stage III clear cel l carcinoma. However, focal positive p53 staining was noted in another five tumors, Of the six tumors showing positive immunohistochemistry, p53 alter ations were noted in four tumors. Three tumors revealed a missense point mu tation: two were in exon 7 (TCT227 -->TTT and GGC(245) --> AGC) and one was in exon 5 (CGC(156) --> CAC). Another tumor revealed a 12-bp deletion in t wo possible ways: it might involve the last four codons at the 3' end of ex on 4 (nucleotides 12,288-12,299) or it might cross over the splice junction between exon 4 and intron 4 (nucleotides 12,290-12,301). The former would result in a predicted protein product of 389 amino acids whereas the latter would cause a frameshift in the gene sequence and would result in a trunca ted protein. Conclusion. Mutations in p53 appear to be much less frequent in clear cell carcinoma than in other histologic types of epithelial ovarian cancer. We s uggest that p53 alterations may not play an important role in the developme nt of clear cell carcinoma.