Objective: The early natural history of epithelial ovarian carcinoma remains poorly understood. Mutation of the TP53 gene is common in advanced-stage (III-IV) ovarian cancers, but less well described in early stage (I-II) tumors. The purpose of this study was to perform a comprehensive analysis of TP53 mutation and p53 expression status in early stage ovarian carcinomas.
Methods: Seventy-three cases of various histologic types, including 46 stage I and 27 stage II tumors, were subjected to direct sequence analysis of the entire TP53 coding region and exon-intron junctions as well as immunohistochemical assessment of p53 expression.
Results: Overall, mutations were identified in 24 of 73 (34%) cases. However, a significant difference in the distribution of mutations among histologic types was observed; TP53 mutations were present in 14 of 21 (67%) serous cancers and 11 of 52 (21%) non-serous cancers (P = 0.0002). Mutations were equally common between stage I and stage II tumors of serous histology. With respect to the correlation between TP53 mutation and p53 immunopositivity, the sensitivity (58%), specificity (71%), positive predictive value (64%), and negative predictive value (83%) were not sufficiently robust to justify use of p53 expression as a surrogate or screen for mutation.
Conclusions: These data indicate that TP53 mutation is common in early stage ovarian carcinomas of serous histology, with a mutation frequency comparable to that reported for advanced-stage tumors, and is therefore likely to occur early in the progression of the most common histologic variant of ovarian carcinoma.