Test Id : IHC
Mismatch Repair (MMR) Protein Immunohistochemistry Only, Tumor
Useful For
Suggests clinical disorders or settings where the test may be helpful
Evaluating tumor tissue to identify patients at risk for having hereditary nonpolyposis colon cancer/Lynch syndrome
Additional Tests
Lists tests that are always performed, at an additional charge, with the initial tests.
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| MLH1I | MLH-1, Immunostain | No, (Bill only) | Yes |
| MSH2I | MSH-2, Immunostain | No, (Bill only) | Yes |
| MSH6I | MSH-6, Immunostain | No, (Bill only) | Yes |
| PMS2I | PMS-2, Immunostain | No, (Bill only) | Yes |
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
When this test is ordered, MLH1, MSH2, MSH6, and PMS2 stains will always be performed at an additional charge.
For more information see Lynch Syndrome Testing Algorithm.
Method Name
A short description of the method used to perform the test
Immunohistochemistry (IHC)
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
HNPCC testing
Immunohistochemistry (IHC)
Lynch syndrome
Mismatch Repair (MMR) Protein Immunohistochemistry
IHCO
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
When this test is ordered, MLH1, MSH2, MSH6, and PMS2 stains will always be performed at an additional charge.
For more information see Lynch Syndrome Testing Algorithm.
Specimen Type
Describes the specimen type validated for testing
Varies
Necessary Information
Pathology report (final or preliminary) at minimum containing the following information must accompany specimen for testing to be performed:
1. Patient name
2. Block number-must be on all blocks, slides, and paperwork (can be handwritten on the paperwork)
3. Tissue collection date
4. Source of the tissue
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Tumor tissue is required.
Preferred:
Specimen Type: Tissue block
Collection Instructions: Submit formalin-fixed, paraffin-embedded tissue block.
Acceptable:
Specimen Type: Tissue slide
Slides: 1 Hematoxylin and eosin stained and 10 unstained
Collection Instructions: Submit 1 slide stained with hematoxylin and eosin and 10 unstained, nonbaked slides (5-micron-thick sections) of tumor tissue.
Special Instructions
Library of PDFs including pertinent information and forms related to the test
Forms
1. Molecular Genetics: Inherited Cancer Syndromes Patient Information (T519)
2. If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Specimens that have been decalcified (all methods) Specimens that have not been formalin-fixed, paraffin-embedded Bone marrow in EDTA | Reject |
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Refrigerated | |||
Useful For
Suggests clinical disorders or settings where the test may be helpful
Evaluating tumor tissue to identify patients at risk for having hereditary nonpolyposis colon cancer/Lynch syndrome
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
When this test is ordered, MLH1, MSH2, MSH6, and PMS2 stains will always be performed at an additional charge.
For more information see Lynch Syndrome Testing Algorithm.
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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.
For more information see Lynch Syndrome Testing Algorithm
Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Interpretation
Provides information to assist in interpretation of the test results
The interpretation of molecular biomarker analysis includes an overview of the results and the associated diagnostic, prognostic, and therapeutic implications.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The finding of absent protein expression for 1 or more of the MMR genes tested does not distinguish between somatic and germline mutations.
Because immunohistochemistry (IHC) results may indicate likelihood of a germline alteration, it is recommended that genetic counseling be provided prior to IHC testing.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors may occur in our interpretation of results if information given to us is inaccurate or incomplete.
Supportive Data
Over 1000 patients who have colorectal cancer have been evaluated for these genetic alterations by our laboratory staff (1/2006).
Clinical Reference
Recommendations for in-depth reading of a clinical nature
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. doi: 10.1007/s10689-004-1447-6
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(1):96-104
3. Idos G, Valle L. Lynch syndrome. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews (Internet). University of Washington, Seattle; 2004. Updated February 2, 2021. Accessed December 5, 2023. Available at www.ncbi.nlm.nih.gov/books/NBK1211/
Method Description
Describes how the test is performed and provides a method-specific reference
Immunohistochemistry staining is used to determine the presence or absence of protein expression for MLH1, MSH2, MSH6, and PMS2. Lymphocytes and normal epithelium exhibit strong nuclear staining and serve as positive internal controls for staining of these proteins.(Cunningham JM, Kim CY, Christensen ER, et al. The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas. Am J Hum Genet. 2001;69[4]:780-790; Gill S, Lindor NM, Burgart LJ, et al. Isolated loss of PMS2 expression in colorectal cancers: frequency, patient age, and familial aggregation. Clin Cancer Res. 2005;11[18]:6466-6471)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Varies
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
- Authorized users can sign in to Test Prices for detailed fee information.
- Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
- Prospective clients should contact their account representative. For assistance, contact Customer Service.
Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
88341 MLH1, MLH2, or MLH6 (if appropriate)
88342 PMS2 (if appropriate)
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| IHC | MMR Protein, IHC Only, Tumor | In Process |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 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 |