Hypermethylation of the hMLH1 promoter with absent hMLH1 expression in medullary-type poorly differentiated colorectal adenocarcinoma in the elderly

Mod Pathol. 2004 Feb;17(2):172-9. doi: 10.1038/modpathol.3800018.


To clarify the significance of hMLH1 promoter hypermethylation in the development of medullary-type poorly differentiated colorectal adenocarcinoma, we studied the status of promoter methylation and hMLH1 expression in 23 medullary-type and 12 pleomorphic-type carcinomas, as well as the pathology and microsatellite status. In medullary-type carcinomas, the percentages of cases with promoter methylation (83%) and an absence of hMLH1 expression (91%) were significantly higher than in pleomorphic-type carcinomas (14 and 17%), respectively. The rate of microsatellite instability in the medullary type was significantly higher than that of the pleomorphic type (87 vs 40%, P<0.01). Compared with pleomorphic-type carcinomas, medullary-type carcinomas were significantly associated with hMLH1 promoter methylation, absent expression of hMLH1 protein, microsatellite instability, as well as a proximal location, a Crohn's-like lymphoid reaction, a low incidence of lymph node metastasis, and a favorable outcome. Medullary-type carcinomas accumulated with advancing age, especially in the female. These results indicated that hMLH1 hypermethylation, concurrent with a lack of its protein expression, may play an important role in the development of medullary-type poorly differentiated colorectal adenocarcinomas in the elderly.

Publication types

  • Comparative Study

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Aged*
  • Aged, 80 and over
  • Carcinoma, Medullary / genetics*
  • Carcinoma, Medullary / pathology
  • Carrier Proteins
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA Methylation*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Microsatellite Repeats
  • MutL Protein Homolog 1
  • Neoplasm Proteins
  • Nuclear Proteins
  • Promoter Regions, Genetic
  • Sex Factors


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