BRAF mutation in colorectal carcinomas with signet ring cell component

Abstract

Objective: Signet ring cell carcinoma is a rare subtype of colorectal carcinoma (CRC) with an associated BRAFV600E mutation. We investigated frequencies of BRAF mutation in 28 CRCs containing variable signet ring cell component and their relation with clinicopathologic parameters. Methods: According to the presence of signet ring cell component, tumors were categorized into groups as follows: 0%-9%, 10%-24%, 25%-49%, and >50%. Genomic DNA was isolated and analyzed for BRAF V600E gene mutation by polymerase chain reaction-restriction fragment length polymorphism. Eleven of 28 cases (39.3%) showed BRAFV600E mutation, which was also confirmed by Sanger sequencing. To elucidate the importance of existence of signet ring cell component at the molecular level, we separated cases into two groups with cut-off levels of 10% and 50%, which pertain to percentages of signet ring cells. Results: Seven of 19 cases (36.8%) under the threshold of 50% and four of nine cases (44.4%) over this threshold value demonstrated BRAF mutation. Three of 7 cases (42.8%) featuring <10% signet ring cell component and eight out of 21 cases (38.1%) showing >10% were BRAF mutated. Conclusions: BRAF mutation must be closely associated with the presence of malignant signet ring cells regardless of their percentages.