Mismatch Repair Gene Expression as a Predictor of Tumor Responses in Patients With Rectal Cancer Treated With Preoperative Chemoradiation

Jung Wook Huh, Hee Cheol Kim, Seok Hyung Kim, Yoon Ah Park, Yong Beom Cho, Seong Hyeon Yun, Woo Yong Lee, Hee Chul Park, Doo Ho Choi, Joon Oh Park, Young Suk Park, Ho-Kyung Chun, Jung Wook Huh, Hee Cheol Kim, Seok Hyung Kim, Yoon Ah Park, Yong Beom Cho, Seong Hyeon Yun, Woo Yong Lee, Hee Chul Park, Doo Ho Choi, Joon Oh Park, Young Suk Park, Ho-Kyung Chun

Abstract

This study evaluated the predictive and prognostic value of expression of mismatch repair (MMR) protein, including MLH1, MSH2, and MSH6 in rectal cancer patients with preoperative chemoradiotherapy.MMR protein expression was measured by immunohistochemistry in both pretreatment biopsies (pre-) and pathologic specimens (post-) from 209 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy and radical surgery. The patients were followed for a median period of 44 months.A pathologic complete response (pCR) was observed in 30 patients (14.4%). The expression levels of MLH1, MSH2, and MSH6 were not significantly different between the pCR and non-pCR groups. A multivariate analysis revealed that tumor differentiation, postoperative chemotherapy, and pre-MSH6 expression were independent predictors of overall survival; ypN category and perineural invasion were independent predictors of disease-free survival. The pre-MSH6 expression was significantly associated with tumor budding and expression of all MMR proteins. On multivariate analysis, ypN category and post-MSH6 expression were independent predictors for local recurrence.In our study, we observed the independent prognostic value of MSH6 expression in pretreatment tissue on overall survival and MSH6 expression after chemoradiation on local recurrence. Constitutive MSH6 expression before and after preoperative therapy may be a useful tool for prediction of oncologic outcome in locally advanced rectal cancer.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Immunohistochemical expression of pretreatment MSH6 expression. A, Low expression. B, High expression.
FIGURE 2
FIGURE 2
Overall survival according to the expression of pre-MSH6 and pathological tumor-node-metastasis stage (A) stage I, (B) stage II, (C) stage III, and (D) stage IV.

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