Absence of V600E B-RAF Mutation in MLH1-Negative Endometrial Carcinoma.
Eva Musulen, Ana Maria Munoz-Marmol, Carolina Sanz, Cristina Carrato, Jose Luis Mate, Aurelio Ariza. Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
Background: Lynch syndrome (LS) is caused by germline mutations in the mismatch repair (MMR) system genes, of which those involving the MLH1, MSH2 and MSH6 genes are the most frequent. Among LS-associated neoplasms, colorectal carcinoma (CRC) is the most common and endometrial carcinoma (EC) the second most common. To compare the pathogenesis of these two neoplasms, we have prospectively studied a population screening EC series for the molecular alterations known to occur in LS-associated CRC.
Design: Seventy-eight surgically resected primary ECs were prospectively studied. Immunohistochemistry for MMR gene proteins (MLH1, MSH2, and MSH6) was performed in all cases. This was followed by microsatellite instability (MSI) analysis, with amplification of five different microsatellites (NR21, NR24, NR27, bat25, and bat26), and V600E B-RAF gene sequencing study in MLH1 (-) cases. Bethesda criteria were evaluated and MMR genes mutational analysis was performed in every case.
Results: Of the 78 EC patients studied, 6 were under 50 years of age, 30 were between 51 and 60, and 42 were older than 61. Twenty EC cases were found to be unstable. Of them, 14 were MLH1 (-) and showed wild-type (WT) B-RAF; 3 were MSH2 (-) and MSH6 (-); and 3 were MSH6 (-). No V600E B-RAF mutation was detected in any of the cases studied.
Conclusions: In conclusion, the absence of V600E B-RAF mutation in MLH1 (-) EC cases would indicate that in EC this mutation is not related to hypermethylation in the same way as it is in CRC. Therefore, algorithms for molecular studies of these two neoplasms should reflect this difference.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 163, Wednesday Afternoon