Stains & molecular markers

Topic Completed: 1 December 2016

Minor changes: 1 October 2020

Copyright: 2002-2021,, Inc.

PubMed Search: PMS2 [title]

Rebecca Obeng, M.D.
Page views in 2020: 1,526
Page views in 2021 to date: 65
Cite this page: Obeng R. PMS2. website. Accessed January 19th, 2021.
Definition / general
  • PMS2 is a component of the DNA mismatch repair system
  • The PMS2 gene (on chromosome 7) encodes an endonuclease that forms a heterodimer with MLH1 to form the MutL alpha complex which is activated upon recognition of DNA mismatches, insertions or deletions by MutS alpha and MutS beta heterodimers
Essential features
  • Germ line mutations in PMS2 are associated with increased risk of colorectal cancer, hereditary nonpolyposis colon cancer, Lynch syndrome, Turcot syndrome and endometrial cancer
  • Milder microsatellite instability (less risk of developing cancer compared to MLH1 mutations)
  • Deficiency in PMS2 is usually due to epigenetic repression (via mutations in or hypermethylation of MLH1)
  • PMS1 homolog 2, mismatch repair system component, HNPCC4, PMS2L, PMSL2, MLH4
  • Ubiquitous nuclear expression in normal tissue
  • Genetic alterations in PMS2 contribute to DNA mismatch repair deficiency that leads to microsatellite instability and increased risk of cancer
  • PMS2 is unstable in absence of MLH1
  • Loss of expression of MLH1 due to mutations generally leads to loss of expression PMS2 as well (Adv Anat Pathol 2009;16:405; Exp Rev Mol Diagnostics 2016;16:591)
  • Germline or sporadic mutations in PMS2 lead to microsatellite instability
  • Screening: immunohistochemical (IHC) stain. Loss of nuclear staining suggests microsatellite instability
    • Lack of PMS2 staining is generally due to mutations in MLH1 and raises suspicion for germline mutations (Cancer Treat Rev 2016;51:19)
    • Missense and point mutations that lead to nonfunctional protein can result in false negative results on IHC
  • Confirmatory: molecular studies (PCR for microsatellite instability)
    • High (MSI-H): at least 2 of 5 unstable markers or greater than or equal to 30% of unstable markers
    • Low (MSI-L): one of five unstable markers or less than 30% of unstable markers
Prognostic factors
Case reports
Microscopic (histologic) description
  • Normal staining pattern: nuclear
  • Cytoplasmic staining is abnormal and should not be misinterpreted as normal staining
Microscopic (histologic) images

Contributed by Epitomics
Missing Image

Colon, normal histology epithelium

Images hosted on other servers:

Sequential sections of the same colon crypt

Sequential sections of
a segment of colon
epithelium near a
colorectal cancer

Colon cancer with loss of MLH1 and PMS2

Molecular / cytogenetics description
  • National Cancer Institute recommendations: 5 microsatellite markers (BAT25, BAT26, N2S123, N5S346 and D17S250) for sequencing (Cancer Res 1998;58:5248) (additional markers may be used, however, there is no consensus on which markers to use)
  • Sanger sequencing for germline mutations
  • Multiplex ligation dependent probe amplification for large copy number variant detection
  • Next generation sequencing
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