Document Detail


hMLH1, hMSH2 and cyclooxygenase-2 (cox-2) in sporadic colorectal polyps.
MedLine Citation:
PMID:  18214062     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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). PATIENTS AND 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. CONCLUSION: 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:
Raul Angelo Balbinotti; Ulysses Ribeiro; Paulo Sakai; Adriana Vaz Safatle-Ribeiro; Silvana Sartori Balbinotti; Cristovam Scapulatempo; Venancio Avancini Ferreira Alves; Carlos Eduardo Pereira Corbett; Flair José Carrilho
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  27     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2007 Nov-Dec
Date Detail:
Created Date:  2008-01-24     Completed Date:  2008-02-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  4465-71     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology, University of Caxias do Sul Medical School, Caxias do Sul, RS, Brazil. raulbalbinotti@terra.com.br
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / biosynthesis*
Adenocarcinoma / metabolism
Adult
Aged
Aged, 80 and over
Colonic Polyps / metabolism*
Colorectal Neoplasms / metabolism
Cyclooxygenase 2 / biosynthesis*
Female
Humans
Immunohistochemistry
Male
Middle Aged
MutS Homolog 2 Protein / biosynthesis*
Nuclear Proteins / biosynthesis*
Precancerous Conditions / metabolism*
Rectum / pathology
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/MLH1 protein, human; 0/Nuclear Proteins; EC 1.14.99.1/Cyclooxygenase 2; EC 3.6.1.3/MSH2 protein, human; EC 3.6.1.3/MutS Homolog 2 Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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