Expression of the human mismatch repair gene hMSH2 in normal and neoplastic tissues

Fredrick S. Leach, Kornelia Polyak, Marilee Burrell, Karen A. Johnson, David Hill, Malcolm G. Dunlop, Andrew H. Wyllie, Paivi Peltomaki, Albert De La Chapelle, Stanley R. Hamilton, Kenneth W. Kinzler, Bert Vogelstein

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Abstract

Hereditary nonpolyposis colorectal cancer is caused by inherited mutations of mismatch repair genes. We developed monoclonal antibodies to the prototype human mismatch repair gene hMSH2 and used them to detect an immunoreactive protein of M(r) 100,000 in mismatch-proficient cell lines. In addition, a M(r) 150,000 protein coimmunoprecipitated with the hMSH2 gene product in cell lines expressing hMSH2. Immunohistochemistry demonstrated that the hMSH2 protein was exclusively nuclear. Whereas the hMSH2 protein was expressed in a variety of tissues, the most striking pattern was observed in esophageal and intestinal epithelia, where expression was limited to the replicating compartment. Neoplastic cells within benign and malignant mismatch repair- proficient tumors expressed the protein, but no hMSH2 immunoreactivity was observed in the colorectal tumors of patients with germline hMSH2 mutation. These results have implications for tumorigenic mechanisms and, potentially, for diagnosis.

Original languageEnglish (US)
Pages (from-to)235-240
Number of pages6
JournalCancer Research
Volume56
Issue number2
StatePublished - Jan 15 1996

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Leach, F. S., Polyak, K., Burrell, M., Johnson, K. A., Hill, D., Dunlop, M. G., Wyllie, A. H., Peltomaki, P., De La Chapelle, A., Hamilton, S. R., Kinzler, K. W., & Vogelstein, B. (1996). Expression of the human mismatch repair gene hMSH2 in normal and neoplastic tissues. Cancer Research, 56(2), 235-240.