K-ras mutations in mucinous ovarian tumors: a clinicopathologic 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 mutations at codons 12 and 13 in 95 mucinous ovarian neoplasms. The results were subsequently correlated with the clinicopathologic data.
METHODS: Benign, borderline, and malignant mucinous ovarian tumors were identified microscopically. DNA was extracted from formalin fixed, paraffin embedded tissue, and target sequences were amplified in vitro by polymerase chain reaction. Mutations were detected by the presence of restriction fragment length polymorphisms artificially introduced by the use of mutant amplimers. In tumors containing areas that exhibited different histologic grade, precise microdissection of each of these areas was performed. The results were correlated with the clinical data and the morphologic features of the neoplasms.
RESULTS: The overall frequency 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 borderline, and three malignant) exhibited mutations at codons 12 and 13. In 12 of the 15 tumors with 2 areas showing different histologic grade, identical point mutations were detected separately in both areas.
CONCLUSIONS: The results of this study confirm that K-ras mutations do occur in benign and particularly in malignant mucinous ovarian tumors. The authors' findings support the hypothesis that K-ras mutational activation is an early event in mucinous ovarian tumorigenesis.