K-RAS MUTATIONS IN MUCINOUS OVARIAN-TUMORS - A CLINICOPATHOLOGICAL AND MOLECULAR STUDY OF 95 CASES

BACKGROUND. To assess the role of K-ras mutations in the pathogenesis of mucinous ovarian tumors, the authors looked for K-ras point mutatio ns at codons 12 and 13 in 95 mucinous ovarian neoplasms. The results w ere subsequently correlated with the clinicopathologic data. METHODS. Benign, borderline, and malignant mucinous ovarian tumors were identif ied microscopically. DNA was extracted from formalin fixed, paraffin e mbedded tissue, and target sequences were amplified in vitro by polyme rase chain reaction. Mutations were detected by the presence of restri ction fragment length polymorphisms artificially introduced by the use of mutant amplimers. In tumors containing areas that exhibited differ ent histologic grade, precise microdissection of each of these areas w as performed. The results were correlated with the clinical data and t he morphologic features of the neoplasms. RESULTS. The overall frequen cy of codon 12/13 ras gene mutations was 68%. Codon 12 point mutations were present in 63% of the cases (55.7% of mucinous cystadenomas, 73% of borderline tumors, and 85% of carcinomas). Codon 13 mutations were detected in 11.5% of the tumors (five cystadenomas, three borderline tumors, and three carcinomas). Eight tumors (three benign, two borderl ine, and three malignant) exhibited mutations at codons 12 and 13. In 12 of the 15 tumors with 2 areas showing different histologic grade, i dentical point mutations were detected separately in both areas. CONCL USIONS. The results of this study confirm that K-ras mutations do occu r in benign and particularly in malignant mucinous ovarian tumors. The authors' findings support the hypothesis that K-ras mutational activa tion is an early event in mucinous ovarian tumorigenesis. (C) 1997 Ame rican Cancer Society.