K-ras mutations in Mullerian inclusion cysts associated with serous borderline tumors of the ovary

Objective. Mullerian inclusion cysts (MIC) are small benign appearing gland s that are occasionally noted in lymph nodes and peritoneal biopsies. They occur most frequently in women with serous ovarian tumors, with borderline tumors (SBOT) having a higher incidence than invasive cancers. The aim of t his study was to examine whether MIC and SBOT have identical K-ras mutation s, which would suggest that they are related. Methods. Six patients in whom adequate tissue was available from SBOT, MIC, and normal tissue were identified from a consecutive series of patients wi th SBOT who underwent lymph node sampling from 1992 to 1997 at Duke Univers ity Medical Center. DNA extraction was performed using laser capture microd issection. Exon 1 of the K-ras gene was amplified using PCR and subjected t o single-strand conformation analysis to screen for mutations. Shifted band s were sequenced to confirm the presence of mutations. Results. Mutations in codon 12 of K-ras were found in three of six (50%) SB OT. In two of these three cases, the identical mutation was found in the SB OT and the MIC (gly to val in both cases), but not in the corresponding nor mal DNA. In one case, a mutation was seen in the ovarian tumor (gly to asp) , but not in the corresponding MIC. Conclusions. Mutations in codon 12 of the K-ras gene are a hallmark of sero us borderline tumors. The presence of identical K-ras mutations in some SBO T and their associated MIC suggests that they are related processes. Both m ay arise due to a field effect, or alternatively some MIC may represent met astases from the primary ovarian tumor. (C) 2001 Academic Press.