Pathological Correlates of Microsatellite Instability in Ulcerative Colitis-Associated Colorectal Carcinoma
Huai-Bin M Ko, Noam Harpaz. Mount Sinai School of Medicine, New York
Background: Recognition of characteristics of colorectal cancer (CRC) that correlate with microsatellite instability (MSI) is of prognostic and therapeutic value and is a component of the revised Bethesda criteria for testing for Lynch syndrome. We investigated whether those histological features that correlate with MSI in the general population are useful in the setting of ulcerative colitis (UC)-associated CRC.
Design: A tissue microarray assembled from 47 CRCs resected from patients with UC between 2001-11 was used to evaluate the immunohistochemical expression of mismatch repair (MMR) proteins MLH1, PMS2, MSH6, and MSH2 as a surrogate for MSI. The corresponding original histologic slides were assessed by 2 pathologists for the following pathological variables: tumor infiltrating lymphocytosis (TIL, >2/hpf), Crohn's-like peritumoral infiltrate (CLPI), mucinous histology, dirty necrosis, grade, and anatomical location (right vs. left). Data were analyzed by Fischer's exact test.
Results: Loss of expression of MMR proteins occurred in 9/47 tumors (19%), including joint loss of MLH1 and PMS2 in 8/9 and loss of PMS2 only in 1/9. Of the pathological variables examined, TIL (P=0.0005), CLPI (P=0.02), grade G1 and G3 (P=0.04), and lack of dirty necrosis (P=0.03) were significantly more prevalent in MSI-CRCs compared to microsatellite stable CRCs. Mucinous histology and anatomical site did not correlate with MSI (P=0.47 and P=0.27, respectively).
Conclusions: The prevalence of MSI and corresponding histological features in UC-associated CRCs are similar to those of CRCs in the general population except for lack of correlation with anatomical site and mucinous histology. The latter parameters likely reflect overriding factors related to the pathogenesis of UC-associated CRCs. Loss of PMS2 in one of our UC-associated tumors may indicate concomitant Lynch syndrome, highlighting the importance of immunohistochemical screening for MMR deficiency even in the UC cancer population.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 64, Tuesday Afternoon