1. Loss of expression of DNA mismatch repair proteins in aberrant crypt foci identified in vivo by magnifying colonoscopy in subjects with hereditary nonpolyposic and sporadic colon rectal cancer.
- Author
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Ramírez-Ramírez MA, Sobrino-Cossío S, de la Mora-Levy JG, Hernández-Guerrero A, Macedo-Reyes Vde J, Maldonado-Martínez HA, Alonso-Larraga JO, and Ramírez-Solis ME
- Subjects
- Aberrant Crypt Foci genetics, Aberrant Crypt Foci pathology, Adaptor Proteins, Signal Transducing analysis, Adult, Aged, Aged, 80 and over, Colonoscopy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Colorectal Neoplasms, Hereditary Nonpolyposis pathology, Female, Humans, Immunohistochemistry, Male, Middle Aged, MutL Protein Homolog 1, MutS Homolog 2 Protein analysis, Nuclear Proteins analysis, Aberrant Crypt Foci metabolism, Adaptor Proteins, Signal Transducing biosynthesis, Colorectal Neoplasms metabolism, Colorectal Neoplasms, Hereditary Nonpolyposis metabolism, DNA Mismatch Repair, MutS Homolog 2 Protein biosynthesis, Nuclear Proteins biosynthesis
- Abstract
Purpose: The aims of this study are to characterize the frequency, density, and distribution of aberrant crypt foci (ACF) and its histological features and to determine the frequency of loss of expression of DNA mismatch repair (MMR) proteins of subjects with hereditary nonpolyposic colorectal cancer (HNPCC) and sporadic colon rectal cancer (CRC)., Methods: Patients with HNPCC, first-degree relatives of subjects with HNPCC, sporadic CRC, and average risk subjects of sporadic CRC were included prospectively. Total colonoscopy with chromoendoscopy using methylene blue 0.5% and magnification in the right colon (cecum and 20 cm of the ascending colon) and in the left colon (rectum) was performed; loss of expression of MLH1 and MSH2 was evaluated by immunohistochemistry in confirmed ACF., Results: Fifty-two subjects were included. Thirty-eight of the 119 ACF detected by endoscopy were biopsied. In 14 of the 38 specimens (36.8%), ACF were confirmed by histology (Cohen's kappa, 0.44). In subjects with HNPCC, ACF were identified more frequently in the right segment of the colon than in the left (73.1% vs. 26%); in contrast, ACF predominated in the left segment of the colon (89.3% vs. 10.6%) in subjects with sporadic CRC. There was a loss of MLH1 expression in ACF in subjects with HNPCC., Conclusions: In HNPCC, we found a greater density of ACF in the right colon, and in sporadic CRC, greater density in the left. ACF present loss in the expression of DNA MMR protein and can be used as an early marker in patients with a risk of HNPCC in whom carcinogenesis appears to be accelerated.
- Published
- 2012
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