Age-related alteration in the association of microsatellite instability with absent hMLH1 expression and histological types of colorectal carcinoma

Pathol Int. 2006 Oct;56(10):597-603. doi: 10.1111/j.1440-1827.2006.02014.x.

Abstract

Microsatellite instability (MSI) is present in approximately 15-20% of sporadic colorectal cancers. However, despite the increased prevalence of absent hMLH1 expression and MSI in colorectal cancer in the elderly, few attempts have been made to define it in detail. The aim of the present paper was to correlate age-related alterations in absent hMLH1 expression and MSI with various histological types of colorectal carcinoma. hMLH1 expression and microsatellite status were studied in 184 colorectal carcinomas (49 well-differentiated, 49 moderately differentiated, 49 poorly differentiated adenocarcinomas, and 37 mucinous carcinomas). The prevalence of absent hMLH1 expression was higher in poorly differentiated adenocarcinoma (63%) and mucinous carcinoma (43%) than in well- (8%) and moderately (12%) differentiated adenocarcinomas. MSI was found more frequently in poorly differentiated adenocarcinoma (69%) and mucinous carcinoma (41%) than in well- and moderately differentiated adenocarcinomas (8% and 6%, respectively). Age-related differences in absent hMLH1 expression and MSI were found only in poorly differentiated adenocarcinoma, in which the prevalence of medullary-type carcinoma increased with advancing age. These results indicate that an age-related increase of medullary-type tumors in poorly differentiated adenocarcinoma may play an important role in the increase of absent hMLH1 expression and MSI in colorectal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma, Mucinous / genetics*
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Aging / metabolism
  • Aging / pathology
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Differentiation / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • DNA, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • MutL Protein Homolog 1
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA, Neoplasm
  • MLH1 protein, human
  • Nuclear Proteins
  • MutL Protein Homolog 1