title: Mucinous carcinoma of the colon: correlation of loss of mismatch repair enzymes with clinicopathologic features and survival.
abstract: Colorectal carcinoma with microsatellite instability (MSI-H) has a characteristic clinicopathologic profile, typically forming right-sided, lymphocyte-rich tumors that are often mucinous. Mucinous histology in general has been linked to adverse prognosis in some studies, but not in others. MSI-H carcinoma, in contrast, has a better prognosis than microsatellite stable carcinoma in most studies. We assessed the relationship between MSI status, clinicopathologic features and outcome for 248 consecutive patients with resected mucinous carcinoma. All cases were reviewed to confirm mucinous histology. Immunohistochemical stains for DNA mismatch repair enzymes hMLH1, hMSH2 and hMSH6 were performed on a representative block from each case. Tumors lacking expression of a mismatch repair enzyme were designated MSI-H; all others were classified as microsatellite stable. Age, sex, tumor size, site, grade, stage, growth pattern, Crohn's-like reaction, vascular invasion and number of tumor-infiltrating lymphocytes were evaluated without knowledge of MSI status or patient outcome. 72 (29.3%) mucinous carcinomas were MSI-H. Compared to microsatellite stable mucinous cancers, they were more likely to be right-sided (83.3 vs 48.6%, P<0.001), have a Crohn's -like reaction (65.7 vs 29.8%, P<0.001) and have many tumor infiltrating lymphocytes (72.2 vs 20.8%, P<0.001). MSI-H mucinous cancers presented more often as localized disease (66.7 vs 38.1%, P<0.001) and less often with lymph node (26.4 vs 44.9%) or distant (4.2 vs 16.5%) metastases. In univariate analysis, MSI had a favorable effect on age-adjusted survival (hazard ratio 0.597, P=0.02). In multivariate analysis, age, grade, Crohn's-like reaction and stage were independent predictors of survival, but MSI status was not. In conclusion, MSI-H mucinous carcinomas are right-sided, low-stage tumors with Crohn's-like reaction and tumor-infiltrating lymphocytes. The outcome for MSI-H mucinous carcinoma is better than that of microsatellite-stable mucinous carcinoma, but MSI status is not an independent predictor of survival.
authors.affiliation: Department of Pathology, University of California San Francisco and Veteran Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kakar
authors.forename: Saime
authors.initials: S
authors.lastname: Aksoy
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Burgart
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smyrk
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002288:Adenocarcinoma, Mucinous / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D000367:Age Factors; D000368:Aged; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D015999:Multivariate Analysis; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes