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Test ID: IHC Mismatch Repair (MMR) Protein Immunohistochemistry Only, Tumor

Useful For

Evaluation of tumor tissue to identify patients at risk for having hereditary nonpolyposis colon cancer/Lynch syndrome

Additional Tests

Test ID Reporting Name Available Separately Always Performed
MSH2I MSH-2, Immunostain No, (bill only) Yes
MSH6I MSH-6, Immunostain No, (bill only) Yes
PMS2I PMS-2, Immunostain No, (bill only) Yes
MLH1I MLH-1, Immunostain No, (bill only) Yes

Testing Algorithm

When this test is ordered, MLH1, MSH2, MSH6, and PMS2 stains will always be performed at an additional charge.

 

See Lynch Syndrome Testing Algorithm in Special Instructions.

Method Name

Immunohistochemical Staining

Reporting Name

MMR Protein, IHC Only, Tumor

Specimen Type

Varies


Specimen Required


Tumor tissue is required.

 

Specimen Type: Tissue block and slide

Collection Instructions:

1. Submit formalin-fixed, paraffin-embedded tissue block (preferred) or 1 slide stained with hematoxylin and eosin and 10 unstained, nonbaked slides (5-micron thick sections) of the tumor tissue.

2. Sections should contain tumor tissue.


Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Clinical Information

Hereditary nonpolyposis colon cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant inherited cancer syndrome that predisposes individuals to the development of colorectal, endometrial, gastric, upper urinary tract, and other cancers. Individuals with HNPCC/Lynch syndrome have a germline mutation in 1 of several genes involved in DNA mismatch repair. The majority of mutations associated with HNPCC/Lynch syndrome occur in MSH2 and MLH1; however, mutations in MSH6 and PMS2 have also been identified.

 

There are several strategies for evaluating individuals whose personal or family history of cancer is suggestive of HNPCC/Lynch syndrome. Typically, the first step is to evaluate tumors for the characteristics common to individuals with HNPCC/Lynch syndrome, which include microsatellite instability (presence of numerous alterations in a type of repetitive DNA called microsatellites) and loss of protein expression of 1 or more of the genes associated with HNPCC/Lynch syndrome.

 

Microsatellite instability (MSI) and immunohistochemistry (IHC) are commonly interpreted together to evaluate risk for HNPCC/Lynch syndrome. High levels of MSI within a tumor are suggestive of defective DNA mismatch repair,


however, this finding does not provide information about which gene is involved. IHC is a complementary testing strategy used to evaluate the expression of the MLH1, MSH2, MSH6, and PMS2 proteins in HNPCC/Lynch syndrome-related cancers. Loss of expression of 1 or more of these proteins within the tumor is helpful in identifying which corresponding genes to target for mutation analysis. Although MSI and IHC are best interpreted together, they are also available separately to accommodate clinical situations in which there are barriers to performing these tests concurrently (eg, financial concerns, specimen requirements).

 

IHC alone can determine retention or loss of MLH1, MSH2, MSH6, and PMS2 protein expression. If all 4 proteins are present, the likelihood of HNPCC/Lynch syndrome is reduced, but not eliminated, because approximately 5% of tumors that display MSI also have normal protein expression for these 4 genes. Loss of 1 or more proteins by IHC is suggestive of defective DNA mismatch repair within the tumor and the likelihood of HNPCC/Lynch syndrome is increased. Germline testing (ie, mutation analysis) for the corresponding genes can then be performed to identify the causative germline mutation and allow for predictive testing of at risk individuals.

 

Of note, loss of protein expression by IHC has also been demonstrated in various sporadic cancers, including those of the colon and endometrium. Absence of MLH1 and PMS2 protein expression within a tumor, for instance, is most often associated with a somatic alteration in individuals with an older age of onset of cancer than typical HNPCC/Lynch syndrome families. Therefore, an MSI-H phenotype or loss of protein expression by IHC within a tumor does not distinguish between somatic and germline mutations. Genetic testing of the gene indicated by IHC analysis can help to distinguish between these 2 possibilities. In addition, when absence of MLH1 and PMS2 are observed, the BRMLH / MLH1 Hypermethylation and BRAF Mutation Analysis, Tumor or ML1HM / MLH1 Hypermethylation Analysis, Tumor test may also help to distinguish between a sporadic and germline etiology.

 

It should be noted that this is not a genetic test, but rather stratifies the risk of having an inherited cancer predisposition syndrome, and identifies patients who might benefit from subsequent genetic testing.

 

See Lynch Syndrome Testing Algorithm in Special Instructions for additional information.

Reference Values

An interpretive report will be provided.

Interpretation

An interpretive report will be provided.

Clinical Reference

1. Baudhuin LM, Burgart LJ, Lentovich O, Thibodeau SN: Use of microsatellite instability and immunohistochemistry testing for the identification of individuals at risk for Lynch Syndrome. Fam Cancer 2005;4(3):255-265

2. Shia J, Klimstra DS, Nafa K, et al: Value of immunohistochemical detection of DNA mismatch repair proteins in predicting germline mutation in hereditary colorectal neoplasms. Am J Surg Pathol 2005;29:96-104

Day(s) and Time(s) Performed

Monday through Friday; Varies

Analytic Time

5 days

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

MLH-1, Immunostain

88341 (if appropriate)

 

MSH-2, Immunostain

88341 (if appropriate)

 

MSH-6, Immunostain

88341 (if appropriate)

 

PMS-2, Immunostain

88342 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
IHC MMR Protein, IHC Only, Tumor In Process

 

Result ID Test Result Name Result LOINC Value
53258 Result Summary 50397-9
53259 Result In Process
54443 Interpretation 59465-5
53260 Specimen 31208-2
53261 Source 31208-2
54444 Tissue ID 80398-1
53262 MLH1 IHC 81691-8
53263 MSH2 IHC 81692-6
53264 MSH6 IHC 81693-4
53265 PMS2 IHC 81694-2
53266 Released By 18771-6

Forms

1. Molecular Genetics: Inherited Cancer Syndromes Patient Information (T519) in Special Instructions

2. If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.

Mayo Clinic Laboratories | Gastroenterology Catalog Additional Information:

mml-gi-colon-cancer