Stains & molecular markers
PMS2


Topic Completed: 1 December 2016

Minor changes: 13 April 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: PMS2 [title]

Rebecca Obeng, M.D.
Page views in 2020: 1,526
Page views in 2021 to date: 553
Cite this page: Obeng R. PMS2. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainspms2.html. Accessed April 18th, 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)
Terminology
  • PMS1 homolog 2, mismatch repair system component, HNPCC4, PMS2L, PMSL2, MLH4
Epidemiology
Sites
  • Ubiquitous nuclear expression in normal tissue
Pathophysiology
  • 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)
Etiology
  • Germline or sporadic mutations in PMS2 lead to microsatellite instability
Diagnosis
  • 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
Treatment
Microscopic (histologic) description
  • Normal staining pattern: nuclear
  • Cytoplasmic staining is abnormal and should not be misinterpreted as normal staining
Microscopic (histologic) images

Contributed by Mieke R. Van Bockstal, M.D., Ph.D. and Epitomics
PMS2 deficient endometrioid carcinoma

PMS2 deficient endometrioid carcinoma

PMS2 deficient gastric carcinoma

PMS2 deficient gastric carcinoma

PMS2 proficient colon carcinoma

PMS2 proficient colon carcinoma

PMS2 proficient endometrial carcinosarcoma

PMS2 proficient endometrial carcinosarcoma

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
Back to top
Image 01 Image 02