Defective Mismatch Repair Status was not Associated with DFS and OS in Stage II Colon Cancer Treated with Adjuvant Chemotherapy.
BACKGROUND
Mismatch repair (MMR) status has been proposed, with some controversy, as a prognostic and predictive marker in stage II colon cancer. The aim of this study was to evaluate the association between MMR and survival in stage II colon cancer.


METHODS
A total of 860 patients with curatively resected stage II colon cancer were selected for inclusion between January 2003 and December 2008. Tumors lacking expression of MLH1 and/or MSH2, as determined by immunohistochemistry, were classified as having deficient MMR (dMMR), whereas other tumors were classified as having proficient MMR (pMMR). Clinical risk (CR) factors were used to divide patients into high or standard CR groups.


RESULTS
Of 860 patients, 14.7 % were dMMR, 42.4 % had ≥1 CR factors, and 85.8 % patients received adjuvant chemotherapy. MMR status did not affect disease-free survival (DFS; hazard ratio [HR] 1.191, p = 0.415) or overall survival (OS; HR 1.300, p = 0.344). Among CR factors, only pathologic T4 disease tended to associate with poor OS (HR 1.979, p = 0.071). Adjuvant chemotherapy was associated with better DFS (HR 0.393, p < 0.0001) in patients with pMMR tumors. However, in patients with dMMR tumors, adjuvant chemotherapy was not associated with DFS.


CONCLUSIONS
MMR status did not affect DFS or OS in patients with stage II colon cancer. In patients treated with adjuvant chemotherapy, dMMR was not associated with DFS and OS. However, adjuvant chemotherapy was associated with improved DFS in pMMR patients.
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Jeong Eun
JE
Kim
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Yong Sang
YS
Hong
Department of Preventive Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Hwa Jung
HJ
Kim
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Kyu-Pyo
KP
Kim
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Jae-Lyun
JL
Lee
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Seong Joon
SJ
Park
Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Seok-Byung
SB
Lim
Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
In Ja
IJ
Park
Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Chan Wook
CW
Kim
Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Yong Sik
YS
Yoon
Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Chang Sik
CS
Yu
Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Jin Cheon
JC
Kim
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Kim Ji
KJ
Hoon
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. twkimmd@amc.seoul.kr.
Tae Won
TW
Kim
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D053843:DNA Mismatch Repair; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein