Microsatellite Instability Testing for Hereditary Nonpolyposis Colorectal Cancer Screen (HNPCC)

Abbrev Code:MSI   
Order Code:LAB4646Order Name:Microsat Instability Colon Cancer SCR
Methodology:Polymerase chain reaction (PCR) and capillary electrophoresis
CPT Codes: 81301 x1, G0452 x1
Turnaround Time:Results are reported in 10-14 days.
Special Instructions:A normal sample (used for comparison) should accompany the tumor sample submitted for MSI testing. The normal sample may be blood or non-tumor fresh or fixed tissue. If a paraffin block is received, the lab will prepare an H & E slide, a pathologist will review the slide and estimate the tumor percentage. IMPORTANT: If fresh tissue or paraffin ribbons are sent, include on requisition form the percentage of tumor seen in the sample for MSI testing. For reliable results, the percentage of tumor should be a minimum of 30%.

Collection Instructions

Specimen:A tumor sample and a normal sample should be sent. See collection instructions.
Container:See Collection Instructions
Collection Instructions:A tumor sample and a normal sample should be sent. The normal sample is used for interpretation comparison. The normal sample may be a blood sample or a non-tumor fixed sample. If sending paraffin ribbons, either send 1 slide stained with hematoxylin and eosin for pathologist review or indicate on the requisition form the percentage of tumor in the sample sent for MSI testing.
Causes for Rejection:Fresh tissue or paraffin ribbons submitted and tumor percentage is less than 30%; decalcified tissue.

Processing and Shipping

Specimen Processing:Store formalin-fixed tissue at room temperature. Store fresh tissue in RPMI or phosphate buffered saline at room temperature. Store frozen tissue on dry ice.
Shipping Instructions:Ship formalin-fixed tissue at room temperature. Ship fresh tissue in RPMI or phosphate buffered saline at room temperature. Ship frozen tissue on dry ice.
Test Performed at or Referral Lab UM Molecular Diagnostics (M)  (UMMC East Bank)


Reference Range:By report.

Dysfunction of the DNA mismatch repair system has been associated with sporadic cancers and the hereditary non-polyposis colon cancer syndrome (HNPCC). Biallelic inactivation of the MLH1, MSH2, and MSH6 genes account for nearly 100% of the cancers associated with mismatch repair defects. PMS2 and MLH3 are additional candidate genes awaiting further evaluation. Phenotypically, mismatch repair deficiency is expressed in various ways, one of which is size alterations of genomicmicrosatellite repeats, and the phenomenon is called microsatellite instability (MSI). MSI is a sensitive marker for mismatch repair deficiency.


The incidence of HNPCC in the general population is 1:1000. 15% of all colon cancers demonstrate MSI and 1-5% of all colon cancers are associated with the HNPCC. 16% of all colorectal cancer patients may meet the Bethesda guidelines for HNPCC screening [UMAR, 2004]. Bethesda guidelines may have overall 96% sensitivity and 27% specificity for identifying MSI tumors. Patients meeting these guidelines are screened with an MSI assay.


There are two types of screening assays, Immunohistochemistry for mismatch repair proteins, and PCR for microsatellite markers. The PCR assays may be near 100% sensitive for high MSI (MSI-H). MSI-H is associated with better prognosis in sporadic colon cancers. Immunohistochemistry may be near equally specific as PCR, but not as sensitive.


Slightly more than 50% of suspected cases of HNPCC are confirmed by a genetic test. If no mismatch gene abnormality is identified, the genetic test result is considered non-informative and according to the revised Bethesda guidelines [Umar, 2004], surveillance and counseling recommendations may be the same with either test result.



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