title: hMLH1, hMSH2 and cyclooxygenase-2 (cox-2) in sporadic colorectal polyps.
abstract: BACKGROUND
  Colorectal adenomatous polyps are known as premalignant lesions. Mutations in the mismatch repair (MMR) enzymes hMLH1, hMSH2 and hMSH6 are recognized causes of hereditary non-polyposis colorectal cancer and act by inducing a mutator phenotype characterized by microsatellite instability (MSI). MSI is also detected in sporadic colorectal cancers. Cox-2 is an inducible enzyme that regulates prostaglandin synthesis and it is overexpressed at sites of inflammation, in colorectal adenomatous polyps and cancer. The aim of this study was to evaluate the immunoexpression of hMLH1, hMSH2 and Cox-2 in polyps resected through colonoscopy, and to examine their association with clinicopathological characteristics (age, gender, location, size, histology and grade of dysplasia).
  
  
  METHODS
  One hundred and sixty-seven colonic polyps, 6 normal colonic mucosa samples, and 23 samples of colorectal adenocarcinoma were used in this study. All patients had no family history of colorectal cancer. The samples were prospectively collected and immunostained for hMLH1, hMSH2 and Cox-2 using the ABC-immunohistochemistry technique with amplification by biotinylated tyramide. The mean age was 60.2+/-13.8 years (range 21-90 years) and 77 (55.8%) were men.
  
  
  RESULTS
  Tubular adenomas were present in 81.4%, tubulous-villous in 15.9%, serrated in 1.8%, and villous in 0.9%. The majority of the adenomas were located in the rectosigmoid region (63.5%), followed by ascendant in 14.2%, cecum in 7.5%, descendent in 8.2% and transverse in 6.7%. Low-grade dysplasia was detected in 59.6% of the adenomas. Loss of hMLH1 and hMLH2 immunoexpression was observed in 20% and 15.5% of the adenomas, respectively. Cox-2 expression was found in 9% of the adenomas, and in 40% of the adenocarcinomas. Moreover, Cox-2 immunoexpression was associated with the multiplicity of adenomas in the same patient (p=0.001). There was no association between marker immunoexpression and gender, age, location, size, histology or grade of dysplasia.
  
  
  CONCLUSIONS
  Loss of hMLH1 and hMLH2 immunoexpression in adenomas is relatively frequent in patients without colorectal cancer family history. Cox-2 is overexpressed in colorectal adenomatous polyps and adenocarcinomas, and its positivity in adenomas may indicate a higher risk for multiple lesions.
authors.affiliation: Department of Gastroenterology, University of Caxias do Sul Medical School, Caxias do Sul, RS, Brazil. raulbalbinotti@terra.com.br
authors.forename: Raul Angelo
authors.initials: RA
authors.lastname: Balbinotti
authors.forename: Ulysses
authors.initials: U
authors.lastname: Ribeiro
authors.forename: Paulo
authors.initials: P
authors.lastname: Sakai
authors.forename: Adriana Vaz
authors.initials: AV
authors.lastname: Safatle-Ribeiro
authors.forename: Silvana Sartori
authors.initials: SS
authors.lastname: Balbinotti
authors.forename: Cristovam
authors.initials: C
authors.lastname: Scapulatempo
authors.forename: Venancio Avancini Ferreira
authors.initials: VA
authors.lastname: Alves
authors.forename: Carlos Eduardo Pereira
authors.initials: CE
authors.lastname: Corbett
authors.forename: Flair José
authors.initials: FJ
authors.lastname: Carrilho
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000230:Adenocarcinoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003111:Colonic Polyps / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis*; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011230:Precancerous Conditions / Q000378:metabolism*; D012007:Rectum / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D051546:Cyclooxygenase 2; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein