title: Association between deficient mismatch repair system and efficacy to irinotecan-containing chemotherapy in metastatic colon cancer.
abstract: The present study investigated the association between deficient mismatch repair (dMMR) and efficacy outcomes of irinotecan-based first-line chemotherapy in patients with metastatic colorectal cancer (mCRC). Among 297 patients with sporadic mCRC receiving an irinotecan-containing regimen as first-line chemotherapy, 197 with available paraffin-embedded tissues were included in the current analysis. Tumors displaying loss of MMR protein (MLH1 or MSH2) and/or a microsatellite instability-high (MSI-H) genotype by PCR were classified as dMMR. Deficient mismatch repair was found in 23 evaluable tumors, among which eight displayed negativity for MLH1 expression, 11 for MSH2 expression, and four for both. The overall response rate was 47.2% (46.0% in proficient MMR (pMMR) and 56.5% in dMMR), with no significant difference between the two groups (P = 0.569). Median progression-free survival was 8.85 months in patients with dMMR tumors and 6.82 months in patients with pMMR tumors, but this difference did not reach statistical significance (P = 0.089). Median overall survival was not different between the two groups (P = 0.413). Efficacy outcomes of first-line irinotecan-based chemotherapy did not differ significantly between mCRC patients with pMMR and those with dMMR. Our data collectively indicate that MMR status is not effective as a single predictive marker for response to irinotecan-based chemotherapy in mCRC patients.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Hong
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Ryu
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.forename: Heung Moon
authors.initials: HM
authors.lastname: Chang
authors.forename: Seok-Byung
authors.initials: SB
authors.lastname: Lim
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Jang
authors.forename: Mi-Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Yu
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
authors.forename: Jin Cheon
authors.initials: JC
authors.lastname: Kim
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D053843:DNA Mismatch Repair / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000077146:Irinotecan; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D002166:Camptothecin