Overexpression of hMSH2 and hMLH1 protein in certain gastric cancers and their surrounding mucosae

Oncol Rep. 2008 Feb;19(2):401-6.


Mismatch repair (MMR) deficiency is closely related to oncogenesis, which is usually accompanied with the loss of expression of hMSH2 and/or hMLH1. These two proteins are detected in many gastric cancers (GCs), and even their overexpression have been reported in certain other cancers. We studied the protein expression levels of MMR (hMSH2 and hMLH1), PCNA and Ki67 in the cancers and surrounding mucosae (SMs) collected from the patients with GC and gastric mucosa samples from non-cancer patients (NCMs), using immunohistochemistry. Our results demonstrated that the positive MMR protein expression levels were 69.1% (132/191), 33.1% (44/133) and 7.1% (3/42) in GCs, SMs and NCMs, respectively (P<0.001); the positive PCNA protein expression levels were 92.1% (176/191), 75.9% (101/133) and 23.8% (10/42), respectively (P<0.001); the positive Ki67 protein expression levels were 79.1% (68/86), 29.2% (21/72) and 45.2% (19/42), respectively (P<0.001). In addition, the MMR protein expression significantly correlated to the level of PCNA protein expression (rs=0.170, P=0.019), but not to the level of Ki67 protein expression in GCs. Notably, the overexpression of MMR protein was not correlated to either PCNA or Ki67 protein expression in SMs and NCMs. These results support the evidence that MMR protein expression may increase prior to gastric cancer occurrence, and in a view of early diagnosis, the detection of MMR protein by IHC may be helpful as a marker in early prediction of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Aged
  • Cell Transformation, Neoplastic / metabolism*
  • Female
  • Gastric Mucosa / enzymology*
  • Gastric Mucosa / pathology
  • Humans
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / analysis
  • MutS Homolog 2 Protein / metabolism*
  • Nuclear Proteins / analysis
  • Nuclear Proteins / metabolism*
  • Proliferating Cell Nuclear Antigen / analysis
  • Proliferating Cell Nuclear Antigen / metabolism
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / etiology*
  • Stomach Neoplasms / pathology


  • Adaptor Proteins, Signal Transducing
  • Ki-67 Antigen
  • MLH1 protein, human
  • Nuclear Proteins
  • Proliferating Cell Nuclear Antigen
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein