Evaluation of microsatellite instability in routine examinations of surgical samples

Indian J Pathol Microbiol. 2022 Jan-Mar;65(1):87-92. doi: 10.4103/IJPM.IJPM_1398_20.

Abstract

Context: Approximately 20%-30% of colon cancer cases have a hereditary basis. The genetic defect may involve mismatch repair (MMR) genes, which results in microsatellite instability (MSI). MMR-deficient colorectal cancer may occur due to germline mutation (Lynch syndrome) or be a sporadic one. A tumor's histological features, supported by a panel of immunohistochemistry stains, enables pathologists to assess the MMR status, which in turn has beneficial effects on clinical management.

Aims: We aimed to show the relations between histopathological features identified during routine examinations and MMR genes' mutations.

Methods and material: We reviewed retrospectively the material of the Department of Pathology fulfilling the revised Bethesda Guidelines.

Statistical analysis used: We used Chi-square test, Spearman test, and epidemiological analysis.

Results: For the PMS2 gene, the positive predictive value (PPV) indicates that 91% of cases neither present any histological lesions nor have genetic abnormalities. The negative predictive value (NPV) indicates that only 50% of cases have both histological and genetic changes. For the MSH6 gene, the PPV indicates that 85% of tumors without specific histological features do not have genetic abnormalities.

Conclusions: We advise universal staining for MLH1, MSH2, MSH6, and PMS2 in every newly diagnosed colon cancer, but due to costly analyses we suggest a protocol for the selection of cases for MMR examinations.

Keywords: Colorectal carcinoma (CRC); lynch syndrome (LS); microsatellite instability (MSI); mismatch repair (MMR).

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • DNA Mismatch Repair
  • Female
  • Humans
  • Immunohistochemistry / methods*
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2 / genetics
  • Predictive Value of Tests
  • Retrospective Studies
  • Specimen Handling / methods*
  • Surgical Procedures, Operative*

Substances

  • PMS2 protein, human
  • Mismatch Repair Endonuclease PMS2