Test Catalog

Test Id : PMS2

PMS2 Immunostain, Technical Component Only

Useful For
Suggests clinical disorders or settings where the test may be helpful

Evaluation of tumor tissue to identify patients at high risk for having hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome

 

Evaluation of tumor tissue to identify patients at risk for having hereditary endometrial carcinoma

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
IHTOI IHC Initial, Tech Only No No
IHTOA IHC Additional, Tech Only No No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

PMS2 IHC, Tech Only

Aliases
Lists additional common names for a test, as an aid in searching

ISPMS2IHCTO

Mismatch Repair (MMR) Protein Immunohistochemistry

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Specimen Type
Describes the specimen type validated for testing

TECHONLY

Ordering Guidance

This test includes only technical performance of the stain (no pathologist interpretation is performed). If diagnostic consultation by a pathologist is required, order PATHC / Pathology Consultation.

Shipping Instructions

Attach the green pathology address label and the pink Immunostain Technical Only label included in the kit to the outside of the transport container.

Necessary Information

If sending normal and tumor blocks; indicate the block number to be stained in performing lab notes (electronic orders) or on the enclosed paperwork (manual orders).

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Supplies: Immunostain Technical Only Envelope (T693)

Specimen Type: Tissue

Container/Tube: Immunostain Technical Only Envelope

Preferred: 2 Unstained positively charged glass slides (25- x 75- x 1-mm) per test ordered; sections 4-microns thick

Acceptable: Formalin-fixed, paraffin-embedded (FFPE) tissue block

Digital Image Access

Forms

If not ordering electronically, complete, print, and send a Immunohistochemical (IHC)/In Situ Hybridization (ISH) Stains Request (T763) with the specimen.

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Wet/frozen tissue
Cytology smears
Nonformalin fixed tissue
Nonparaffin embedded tissue
Noncharged slides
ProbeOn slides
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
TECHONLY Ambient (preferred)
Refrigerated

Useful For
Suggests clinical disorders or settings where the test may be helpful

Evaluation of tumor tissue to identify patients at high risk for having hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome

 

Evaluation of tumor tissue to identify patients at risk for having hereditary endometrial carcinoma

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant hereditary cancer syndrome associated with germline variants in the mismatch repair genes: MLH1, MSH2, MSH6, and PMS2.

 

HNPCC is predominantly characterized by significantly increased risks for colorectal and endometrial cancer. The lifetime risk for colorectal cancer is highly variable and dependent on the gene involved. The risk for colorectal cancer associated MLH1 and MSH2 variants (approximately 50%-80%) is generally higher than the risks associated with variants in the other HNPCC-related genes and the lifetime risk for endometrial cancer (approximately 25%-60%) is also highly variable. Other malignancies within the tumor spectrum include sebaceous neoplasms, gastric cancer, ovarian cancer, hepatobiliary and urinary tract carcinomas, and small bowel cancer. The lifetime risks for these cancers are less than 15%. Of the 4 mismatch repair genes, variants within the PMS2 gene confer the lowest risk for any of the tumors within the HNPCC spectrum.

 

Several clinical variants of HNPCC have been defined. These include Turcot syndrome, Muir-Torre syndrome, and homozygous mismatch repair variants (also called constitutional mismatch repair deficiency syndrome). Turcot syndrome and Muir-Torre syndrome are associated with increased risks for cancers within the tumor spectrum described but also include brain and central nervous system malignancies and sebaceous carcinomas, respectively. Homozygous or compound heterozygous mismatch repair alterations, characterized by the presence of biallelic deleterious alterations within a mismatch repair gene, are associated with a different clinical phenotype defined by hematologic and brain cancers, cafe au lait macules, and childhood colon or small bowel cancer.

 

There are several strategies for evaluating individuals with a personal or family history of cancer suggestive of HNPCC. Testing tumors from individuals at risk for HNPCC for microsatellite instability (MSI) indicates the presence or absence of defective DNA mismatch repair phenotype within the tumor but does not suggest in which gene the abnormality rests. Tumors from individuals affected by HNPCC usually demonstrate an MSI-H phenotype (MSI >30% of microsatellites examined). The MSI-H phenotype can also be seen in individuals whose tumors have somatic MLH1 promoter hypermethylation. Tumors from individuals that show the MSS/MSI-L phenotype (MSI at <30% of microsatellites examined), are not likely to have HNPCC or somatic hypermethylation of MLH1. Immunohistochemistry (IHC) is a complementary testing strategy to MSI testing. In addition to identifying tumors with defective DNA mismatch repair, IHC analysis is helpful for identifying the gene responsible for the defective DNA mismatch repair within the tumor, because the majority of MSI-H tumors show a loss of expression of at least 1 of the 4 mismatch repair genes described above.

 

Testing is typically first performed on the tumor of an affected individual and in the context of other risk factors, such as young age at diagnosis or a strong family history of HNPCC-related cancers. If defective DNA mismatch repair is identified within the tumor, variant analysis of the associated gene can be performed to identify the causative germline variant and allow for predictive testing of at-risk individuals.

 

Of note, MSI-H phenotypes and loss of protein expression by IHC have 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 families. Therefore, an MSI-H phenotype or loss of protein expression by IHC within a tumor does not distinguish between somatic and germline alterations. Genetic testing of the gene indicated by IHC analysis can help to distinguish between these 2 possibilities. In addition, when absence of MLH1/PMS2 is observed, BRMLH / MLH1 Hypermethylation and BRAF Mutation Analyses, Tumor or ML1HM / MLH1 Hypermethylation Analysis, Tumor may also help to distinguish between a sporadic and germline etiology.

 

It should be noted that this HNPCC screen 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.

Interpretation
Provides information to assist in interpretation of the test results

This test does not include pathologist interpretation, only technical performance of the stain. If interpretation is required order PATHC / Pathology Consultation for a full diagnostic evaluation or second opinion of the case.

 

The positive and negative controls are verified as showing appropriate immunoreactivity and documentation is retained at Mayo Clinic Rochester. If a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is available upon request; call 855-516-8404.

 

Interpretation of this test should be performed in the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Age of a cut paraffin section can affect immunoreactivity. Stability thresholds vary widely among published literature and are antigen dependent. Best practice is for paraffin sections to be cut within 6 weeks.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Burgart LJ: Testing for defective DNA mismatch repair in colorectal carcinoma: a practical guide. Arch Pathol Lab Med. 2005 Nov;129(11):1385-1389

2. Klarskov L, Ladelund S, Holck S, et al: Interobserver variability in the evaluation of mismatch repair protein immunostaining. Hum Pathol. 2010 Oct;41(10):1387-1396

3. Lanza G, Gafa R, Maestri I, Santini A, Matteuzzi M, Cavazzini L: Immunohistochemical pattern of MLH1/MSH2 expression is related to clinical and pathological features in colorectal adenocarcinomas with microsatellite instability. Mod Pathol. 2002 Jul;15(7):741-749

4. Modica I, Soslow RA, Black D, Tornos C, Kauff N, Shia J: Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma. Am J Surg Pathol. 2007 May;31(5):744-751

5. Mojtahed A, Schrijver I, Ford JM, Longacre TA, Pai RK: A two-antibody mismatch repair protein immunohistochemistry screening approach for colorectal carcinomas, skin sebaceous tumors, and gynecologic tract carcinomas. Mod Pathol. 2011 Jul;24(7):1004-1014

6. Rigau V, Sebbagh N, Olschwang S, et al: Microsatellite instability in colorectal carcinoma. The comparison of immunohistochemistry and molecular biology suggests a role for hMLH6 [correction of hMLH6] immunostaining. Arch Pathol Lab Med. 2003 Jun;127(6):694-700

7. Shia J: Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. J Mol Diagn. 2008 Jul;10(4):293-300

8. Salem ME, Bodor JN, Puccini A, et al: Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors. Int J Cancer. 2020 Nov 15;147(10):2948-2956. doi: 10.1002/ijc.33115

Method Description
Describes how the test is performed and provides a method-specific reference

Immunohistochemistry on sections of paraffin-embedded tissue.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

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.

Monday through Friday

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.

1 to 3 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Until staining is complete.

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

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 Regional Manager. 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 using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test 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.

88342-TC, primary

88341-TC, if additional IHC

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
PMS2 PMS2 IHC, Tech Only Order only;no result
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.
70852 PMS2 IHC, Tech Only Bill only; no result

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports