N78: In Contrast To Subjects With Lynch Syndrome, The Adenomatous Polyps From Subjects With Sporadic MSI-High Tumors Have Normal Expression Of MMR Proteins

A. Vilkin1, S. Morgenstern2, H. Weiss2, L. Haiiman Mantzur2, Y. Sternov2, Y. Goldberg1, I. Dotan1, Y. Niv1, Z. Levi1

1 – Division of Gastroenterology,  Rabin Medical Center, Petach Tikva, Israel. 2 – Department of  Pathology,  Rabin Medical Center,  Petach Tikva, Israel.


Aim: Polyps from patients with Lynch Syndrome (LS) may show loss of expression of  Mismatch Repair (MMR) proteins. Data about MMR expression in polyps  from patients with sporadic MSI-high colorectal cancer is lacking. We  investigated whether polyps form patients with sporadic MSI-High tumor may also show loss of MMR proteins expression.

Method: We performed IHC stain for four MMR proteins of adenomatous polyps from patients with sporadic MSH-high CRC vs. polyps from patients with LS. Sporadic MSI-high cancers were defined  as tumors  with  loss of  MLH1/PMS2  & BRAF V600E mutated.

Results: 70 adenomatous polyps were analyzed: 22 from patients with sporadic MSH-High (81.8% women, median age 68.0 [IQR 61.7-86.2]) and 48 from LS patients (37.5% women, median age 48.5 [IQR 39.2-63.7]). Overall, none (0/22) polyps of the sporadic MSH-High group and 45.8 % (22/48) of the LS group showed loss of MMR protein stain (p<0.001). Of the LS group polyps, 41.5 %( 17/41) of polyps <10 mm and 71.4% (5/7) of polyps ≥10mm showed loss of protein expression p=0.145.

Conclusion: In contrast to LS, polyps from patients with sporadic MSI-high CRC do not show loss of MMR proteins. This may suggest that loss of MLH1 is a late event in the sporadic cases.