Clinicopathologic Features of Microsatellite Instability-High (MSI-H) Colorectal Carcinomas in Patients >60 Years of Age
Huankai Hu, Douglas J Hartman, Randall E Brand, Nathan Bahary, Beth Dudley, Simon I Chiosea, Marina N Nikiforova, Reetesh K Pai. University of Pittsburgh, Pittsburgh, PA
Background: The Revised Bethesda Guidelines (RBG) for screening colorectal carcinomas (CRCs) to identify patients with Lynch syndrome (LS) provide no recommendations for microsatellite instabiltiy (MSI) testing in patients >60 years of age. We analyzed MSI-H CRCs identified in patients >60 years in an attempt to identify pathologic features which can help to identify LS-associated CRC in this patient population.
Design: 117 consecutive MSI-H CRCs were identified between 2009 to June 2012 in patients >60 years of age by MSI PCR (81 cases), mismatch repair protein (MMR) immunohistochemistry (14 cases), or both MSI PCR and MMR IHC (22 cases). All cases were analyzed for the RBG MSI-H histologic features of tumor-infiltrating lymphocytes (TILs), Crohn's-like lymphocytic reaction, mucinous/signet ring cell differentiation, and medullary growth pattern and additional pathologic features including grade, location, peritumoral lymphocytic reaction, histologic heterogeneity, and stromal plasma cells. MSI-H CRCs were stratified into sporadic and presumed LS-associated based on BRAF V600E mutation, MLH1 promoter hypermethylation, family and personal cancer-related history (Amsterdam I or II criteria), and germline MMR gene mutation analysis.
Results: Ten of 117 (8.5%) MSI-H CRCs were LS-associated. LS-associated CRCs were more frequently located in the left colon/rectum compared with sporadic MSI-H CRC (3/10, 30% vs. 7/107, 6.5%; p=0.04). There was no significant differences in tumor histology between LS-associated and sporadic MSI-H CRC. Importantly, all 10 LS-associated CRCs demonstrated at least one of the four RBG MSI-H histologic features: 8/10 Crohn's-like peri-tumoral reaction; 7/10 TILs; 5/10 mucinous/signet ring histology; and 1/10 medullary histology. Most (100/107, 93%) sporadic MSI-H demonstrated at least one of the four RBG MSI-H histologic features.
Conclusions: In patients >60 years, 8.5% of MSI-H CRC are LS-associated. All LS-associated CRCs exhibited at least one of the RBG MSI-H histologic features. Our results indicate that in patients >60 years of age, the presence of any RBG MSI-H histologic features should prompt MSI screening to identify Lynch syndrome. Importantly, evaluation for RBG MSI-H histologic features should be performed on CRCs in patients >60 years of age regardless of tumor location as LS-associated CRCs can occur in the left colon and rectum.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 91, Wednesday Morning