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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

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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.

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Acknowledgements

The authors would like to thank Luis Alonso Herrera Montalvo PhD, Cancer Biomedical Research Unit of the UNAM/INCan, for the support to complete this investigation.

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The authors report that there are no disclosures to this publication.

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Authors and Affiliations

  1. Department of Gastrointestinal Endoscopy, Instituto Nacional de Cancerología (INCan), México City, Mexico

    Miguel Angel Ramírez-Ramírez, Sergio Sobrino-Cossío, José Guillermo de la Mora-Levy, Angélica Hernández-Guerrero, Juan Octavio Alonso-Larraga & Mauro Eduardo Ramírez-Solis

  2. Department of Pathology, INCan, México City, Mexico

    Verónica de Jesús Macedo-Reyes & Héctor Aquiles Maldonado-Martínez

  3. Instituto Nacional de Cancerología de México, San Fernando 22, Tlalpan, 14080, México, D.F., Mexico

    Miguel Angel Ramírez-Ramírez, Verónica de Jesús Macedo-Reyes & Héctor Aquiles Maldonado-Martínez

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  1. Miguel Angel Ramírez-Ramírez
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  2. Sergio Sobrino-Cossío
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Correspondence to Miguel Angel Ramírez-Ramírez.

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Ramírez-Ramírez, M.A., Sobrino-Cossío, S., de la Mora-Levy, J.G. et al. 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. J Gastrointest Canc 43, 209–214 (2012). https://doi.org/10.1007/s12029-011-9303-z

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