title: Mismatch Repair Gene Expression as a Predictor of Tumor Responses in Patients With Rectal Cancer Treated With Preoperative Chemoradiation.
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.
authors.affiliation: From the Department of Surgery (JWH, HCK, YAP, YBC, SHY, WYL); Department of Pathology (SHK); Department of Radiation Oncology (HCP, DHC); Department of Hematology-Oncology, Samsung Medical Center (JOP, YSP); and Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea (H-KC).
authors.forename: Jung Wook
authors.initials: JW
authors.lastname: Huh
authors.forename: Hee Cheol
authors.initials: HC
authors.lastname: Kim
authors.forename: Seok Hyung
authors.initials: SH
authors.lastname: Kim
authors.forename: Yoon Ah
authors.initials: YA
authors.lastname: Park
authors.forename: Yong Beom
authors.initials: YB
authors.lastname: Cho
authors.forename: Seong Hyeon
authors.initials: SH
authors.lastname: Yun
authors.forename: Woo Yong
authors.initials: WY
authors.lastname: Lee
authors.forename: Hee Chul
authors.initials: HC
authors.lastname: Park
authors.forename: Doo Ho
authors.initials: DH
authors.lastname: Choi
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Ho-Kyung
authors.initials: HK
authors.lastname: Chun
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059248:Chemoradiotherapy / Q000379:methods*; D003131:Combined Modality Therapy; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011379:Prognosis; D012004:Rectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000601:surgery / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
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