Reduced Pms2 expression in non-neoplastic flat mucosa from patients with colon cancer correlates with reduced apoptosis competence

Harris Bernstein, Anil P Rama Rao, Hana Holubec, Carol Bernstein, Claire M. Payne, Lois Ramsey, Katerina Dvorakova, Megan Wilson, James A Warneke, Harinder Garewal

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Pms2 protein is a component of the DNA mismatch repair complex responsible both for post-replication correction of DNA nucleotide mispairs and for early steps in apoptosis. Germline mutations in DNA mismatch repair genes give rise to hereditary non-polyposis colon cancer, which accounts for about 4% of colon cancers. However, little is known about the expression of mismatch repair proteins in relation to sporadic colon cancer, which accounts for the great majority of colon cancers. Multiple samples were taken from the non-neoplastic flat mucosa of colon resections from patients with no colonic neoplasia, a tubulovillous adenoma, or an adenocarcinoma. Expression of Pms2 was assessed using semiquantitative immunohistochemistry. Apoptosis was assessed in polychrome-stained epoxy sections using morphologic criteria. Samples from patients without colonic neoplasia had moderate to strong staining for Pms2 in cell nuclei at the base of crypts, while samples from 2 of the 3 colons with a tubulovillous adenoma, and from 6 of the 10 colons with adenocarcinomas, showed reduced Pms2 expression. Samples from patients with an adenocarcinoma that had reduced Pms2 expression also exhibited reduced apoptosis capability in nearby tissue samples, evidenced when this paired tissue was stressed ex vivo with bile acid. Reduced Pms2 expression in the colonic mucosa may be an early step in progression to colon cancer. This reduction may cause decreased mismatch repair, increased genetic instability, and/or reduced apoptotic capability. Immunohistochemical determination of reduced Pms2 expression, upon further testing, may prove to be a promising early biomarker of risk of progression to malignancy.

Original languageEnglish (US)
Pages (from-to)166-172
Number of pages7
JournalApplied Immunohistochemistry and Molecular Morphology
Volume14
Issue number2
DOIs
StatePublished - Jun 2006

Fingerprint

DNA Mismatch Repair
Colonic Neoplasms
Mental Competency
Mucous Membrane
Apoptosis
Colon
Adenocarcinoma
Adenoma
Neoplasms
Germ-Line Mutation
Cell Nucleus
Bile Acids and Salts
DNA Replication
Proteins
Nucleotides
Biomarkers
Immunohistochemistry
Staining and Labeling
Genes

Keywords

  • Apoptosis
  • Bile acid
  • Colon cancer
  • Mismatch repair
  • Pms2

ASJC Scopus subject areas

  • Anatomy
  • Medical Laboratory Technology

Cite this

Reduced Pms2 expression in non-neoplastic flat mucosa from patients with colon cancer correlates with reduced apoptosis competence. / Bernstein, Harris; Rama Rao, Anil P; Holubec, Hana; Bernstein, Carol; Payne, Claire M.; Ramsey, Lois; Dvorakova, Katerina; Wilson, Megan; Warneke, James A; Garewal, Harinder.

In: Applied Immunohistochemistry and Molecular Morphology, Vol. 14, No. 2, 06.2006, p. 166-172.

Research output: Contribution to journalArticle

Bernstein, Harris ; Rama Rao, Anil P ; Holubec, Hana ; Bernstein, Carol ; Payne, Claire M. ; Ramsey, Lois ; Dvorakova, Katerina ; Wilson, Megan ; Warneke, James A ; Garewal, Harinder. / Reduced Pms2 expression in non-neoplastic flat mucosa from patients with colon cancer correlates with reduced apoptosis competence. In: Applied Immunohistochemistry and Molecular Morphology. 2006 ; Vol. 14, No. 2. pp. 166-172.
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