title: 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.
abstract: OBJECTIVE
  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.
authors: Department of Gastrointestinal Endoscopy, Instituto Nacional de Cancerología (INCan), México City, Mexico. ramirez.ramirez.ma@gmail.com
authors: Miguel Angel
authors: MA
authors: Ramírez-Ramírez
authors: Sergio
authors: S
authors: Sobrino-Cossío
authors: José Guillermo
authors: JG
authors: de la Mora-Levy
authors: Angélica
authors: A
authors: Hernández-Guerrero
authors: Verónica de Jesús
authors: Vde J
authors: Macedo-Reyes
authors: Héctor Aquiles
authors: HA
authors: Maldonado-Martínez
authors: Juan Octavio
authors: JO
authors: Alonso-Larraga
authors: Mauro Eduardo
authors: ME
authors: Ramírez-Solis
mesh_terms: D058739:Aberrant Crypt Foci / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis / Q000096:biosynthesis*; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein