Mismatch Repair Status in a Cohort of Rectal Adenocarcinomas before and after Chemoradiation
AM Bellizzi, CD Crowder, WL Marsh, H Hampel, WL Frankel. The Ohio State University Medical Center, Columbus, OH; Brigham and Women's Hospital, Boston, MA
Background: At our institution we have performed mismatch repair immunohistochemistry (MMR IHC) as a screen for Lynch syndrome on all colorectal cancer resections since 2006. Anecdotally we have observed decreased staining in neoadjuvant-treated rectal adenocarcinomas (NTx RA). This diminution is particularly prominent with MSH6, often resulting in an "equivocal" interpretation. We performed this study to systematically evaluate MMR IHC in NTx RA.
Design: We assembled a cohort of 65 matched pretreatment biopsies (bx) and resections (res) from patients receiving NTx for RA. MMR IHC for MLH1, PMS2, MSH2, and MSH6 was performed. Bx and res tissue were stained on the same slide. Tumor IHC was evaluated for intensity (0, 1: less staining than is typical/less staining than internal control, 2: robust staining) and quantity (0-100%) and a score representing the product of these calculated. Intact staining in internal control was required for interpretation. In 14 (22%), res demonstrated a complete response. Mean data was analyzed using Wilcoxon matched-pairs tests, with P < 0.05 considered significant.
Results: Quantitative IHC data is summarized in the table.
|Biopsy (n=65)||Resection (n=51)||P|
|MLH1||191 ± 34||171 ± 52||0.002|
|PMS2||189 ± 36||169 ± 54||0.0005|
|MSH2||191 ± 38||157 ± 67||0.0002|
|MSH6||165 ± 54||81 ± 64||<0.0001|