The role of serous borderline ovarian
tumors (BOTs) in the pathogenesis of serous ovarian
carcinomas is unclear. Some authors have compared mutations in serous BOTs to those in serous ovarian
carcinomas, but the data on two common oncogenes, p53 and K-ras, remain inconclusive. To further clarify the relationship between the two
tumors, we performed mutational analysis on
tumors from a set of eight patients who first presented with advanced-stage serous BOTs and later developed grade 1 serous
carcinomas. Epithelium from eight advanced-stage serous BOTs and subsequent grade 1 papillary serous
carcinomas was microdissected and retrieved using a PixCell
laser-capture microscope. Stroma was dissected as an internal control. The
DNA was extracted with
proteinase K and analyzed by single-strand conformational polymorphism-PCR for p53 and K-ras mutations. Bands with altered motility were analyzed by direct cycle sequencing. Seven of eight patients demonstrated different mutations in the secondary
tumor compared with the primary
tumor. For three patients, p53 mutations were identified in the BOTs that were absent from the
carcinomas, suggesting a nonclonal origin for the
carcinomas. These findings are consistent with the hypothesis that advanced-stage serous BOTs represent a distinct pathological entity compared with grade 1 serous
epithelial ovarian carcinoma.