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Microsatellite Instability Marker Profile by Immunohistochemistry (IHC)

Test Code

I MSI

Test Synonyms

MLH1, MSH2, MSH6, PMS2

Associations

HNPCC (Hereditary non-polyposis colorectal cancer); Lynch syndrome; Mismatch repair gene mutations;
Fluoracil

Test Code Description
I MSI Microsatellite Instability Profile
I MLH1 Microsatellite Instability MLH1
I MSH2 Microsatellite instability MSH2, Melanocyte Stimulating Hormone, FE11
I MSH6 Microsatellite instability MSH6, BC/44
I PMS2 Microsatellite instability PMS2, A16-4

 

Methodology

Immunohistochemistry

Turnaround Time

2 days

Specimen Requirements
  • Surgical samples received in 10% neutral buffered formalin
  • Formalin fixed paraffin embedded tissue
  • Previously prepared pathology materials (slides,smears, blocks or other samples)

Send reports, history and differential diagnosis

Specimen Stability
Indefinitely at room temperature
Storage & Handling

Ship ambient. In extreme hot weather, ship with a cool pack.

Causes for Rejection

Inadequate fixation; Improper labeling

Reference Range

Marker and tissue specific

Description

The importance of mismatch repair genes became apparent with the identification of the genetic basis for hereditary nonpolyposis colon cancer (HNPC). MSH-2 is involved in the initial cognition of mismatch nucleotides during the replication mismatch repair process. It is thought that after MSH-2 binds to a mismatched DNA duplex it is joined by a heterodimer of MLH-1 and PMSH, which together help facilitate the later steps in mismatch repair.

A subset of HNPCC patients as well as some colorectal cancer patients are predisposed to cancer caused by germline muatations in the DNA mismatch repair (MMR) genes. Identification of inherited MMR mutations, besides impacting care and survelillance of the patient also enables familial predictive testing.

Individuals with mutations in one of the MMR genes are defined as having Lynch Syndrome. The revised Bethesda guidelines established criteria to identify at risk individuals. It is generally recommended that patients at increased risk for Lynch syndrome undergo pre-screening with microsatellite instability analysis by immunohistochemistry. Loss of particular MMR protein can direct which genes to evaluate by germline mutation analysis.

Immunohistochemistry studies have further determined that the microsatellite instability phenotype in endometrial carcinoma is linked to defects in the MLH1/PMS2 gene.

References
  1. Sepulveda A.R. (2007). The importance of Microsatellite Instability in Colonic Neoplasms. ASCP Annual Meeting.
  2. PiƱol V. et al. (2005). Accuracy of Revised Bethesda Guidelines,Microsatellite Instability, and Immunohistochemistry for the Identification of Patients With Hereditary Nonpolyposis Colorectal Cancer. JAMA. 293:1986-1994
  3. Asad Umar et al. (2004). Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability (2004) J Natl Cancer Inst.96(4):261-8
  4. Boland, C.R., et al.(1998). A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Research.58(22): 5248-5257
  5. Gatalica Z, Torlakovic E.(2008). Pathology of the hereditary colorectal carcinoma. Fam Cancer.7(1):15-26.