title: Sporadic colorectal cancers with defective mismatch repair display a number of specific morphological characteristics: relationship between the expression of hMLH1 and hMSH2 proteins and clinicopathological features of 273 adenocarcinomas.
abstract: OBJECTIVE
  The aim of this study was to assess the independent value of pathological criteria in the diagnosis of mismatch repair (MMR)-defective sporadic colorectal cancers.
  
  
  RESULTS
  Resected colorectal adenocarcinomas (n = 273) were reviewed in order to identify a number of specific morphological features of MMR-defective carcinomas. Of the 273 cases, 35.2% were right-sided and 5.9% were poorly differentiated. Focal extracellular mucin secretion was seen in 5.1% of cases and a stromal follicular reaction in 4.6%. The expression of the two major MMR proteins hMLH1 and hMSH2 was studied by immunohistochemistry. Carcinomas were considered deficient in the MMR system when a loss of nuclear signal in neoplastic cells was observed for one of the proteins. Such an extinction was seen in 37 of the cases (13.6%). The hMLH1 protein was the one most frequently altered (86.5%). After multivariate analysis, three independent factors were significantly associated with MMR deficiency: proximal location [odds ratio (OR) = 9.30; 95% confidence interval (CI) 2.79, 30.98], the presence of a true stromal follicular reaction (OR = 13.60; 95% CI 2.98, 62.00) and poor differentiation (OR = 8.33; 95% CI 1.63, 40.32).
  
  
  CONCLUSIONS
  These results confirm that sporadic colorectal MMR-defective adenocarcinomas display certain specific morphological characteristics. However, these pathological features are not sufficiently predictive and immunohistochemistry is needed to identify such tumours accurately.
authors.affiliation: Service d'Anatomie Pathologique, CHU Dijon and Registre Bourguignon des Cancers Digestifs, Faculté de Médecine (INSERM EPI 01-06, IFR 100), 7 Boulevard Jeanne d'Arc, 21079 Dijon Cedex, France. caroline.chapusot@u-bourgogne.fr
authors.forename: C
authors.initials: C
authors.lastname: Chapusot
authors.forename: L
authors.initials: L
authors.lastname: Martin
authors.forename: N
authors.initials: N
authors.lastname: Mungra
authors.forename: D
authors.initials: D
authors.lastname: Rageot
authors.forename: A M
authors.initials: AM
authors.lastname: Bouvier
authors.forename: C
authors.initials: C
authors.lastname: Bonithon Kopp
authors.forename: T
authors.initials: T
authors.lastname: Ponnelle
authors.forename: J
authors.initials: J
authors.lastname: Faivre
authors.forename: F
authors.initials: F
authors.lastname: Piard
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D014408:Biomarkers, Tumor / Q000378:metabolism; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009077:Mucins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein