ARUP's Laboratory Test Directory

0049302: Microsatellite Instability/HNPCC by Immunohistochemical Stain

Test Mnemonic: MSI
Methodology: Immunohistochemistry

Performed: Mon-Fri

Reported: Within 5 days

Specimen Required:  
Collect: Paraffin-embedded, formalin-fixed tissue block enriched with colon tumor.

Transport: Paraffin-embedded, formalin-fixed tissue block enriched with colon tumor at 20-25°C. Protect paraffin block from excessive heat. Ship in cooled container during summer months. Include surgical histology report.

Remarks: Only tissue that is clearly carcinoma (established by histological criteria) should be tested.

Unacceptable Conditions: Samples fixed/processed in alternate fixatives (alcohol, Prefer®) should not be submitted.

Stability: Paraffin block: Ambient: Indefinitely; Refrigerated: Acceptable; Frozen: Unacceptable

Reference Interval:
By report

Interpretive Data:
Background Information:

Negative immunostaining with either hMLH1 or hMSH2 correlates well with microsatellite instability (MSI) in a tumor. MSI occurs in nearly all colorectal cancers from individuals with hereditary nonpolyposis colorectal cancer (HNPCC) and in 10-15% of sporadic colon cancer. Since the correlation between MSI and immunostaining is not perfect, a direct measurement of MSI may be helpful.  Refer to Microsatellite Instability/HNPCC by PCR (0050585). Normal immunoreactivity (positive immunostaining) for hMLH1, hMSH2, hMSH6, and hPMS2 correlates well with a lack of MSI, although direct measurement of MSI is necessary to exclude the possibility of instability.

Germline mutations in hPMS2 and hMSH6 are rare causes of  HNPCC, although colonic tumors associated with hMSH6 mutations may not exhibit microsatellite instability.  Loss of hMSH6 or hPMS2 immunostaining may signify a mutation in these genes.  However, it should be noted that tumors with a primary defect in hMLH1 or hMSH2 are often negative by IHC for hPMS2 or hMSH6 respectively.  This is because the stability of hPSM2 is dependent upon its ability to form a complex with hMLH1, and the stability of hMSH6 is dependent upon its ability to form a complex with hMSH2.

This interpretation may not apply to cancers other than colon cancers.

Assay is performed on paraffin-embedded, formalin-fixed tissue.  Antibody clone for hMLH1 is G168-15, hMSH2 is FE11, hMSH6 is 44, and hPMS2 is A16-4.  The detection system is LSAB.

Please refer to Statement B in the Compliance Statements section in the front of the Laboratory Test Directory.



CPT Code(s):
88342 x4