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Test Code Lynch Synd Prot by IHC Lynch Syndrome DNA Mismatch Repair Proteins by IHC

Important Note

Order as "HMISC"

Useful For

These testing algorithms are of utility in evaluating patients for lynch syndrome, when suspected by either clinical or histopathologic parameters; see the Lynch Syndrome Testing Algorithms below.

 

Lynch Syndrome Algorithm for Colorectal Carcinoma

 

Lynch Syndrome Algorithm for Endometrial Carcinoma

Synonyms/Keywords

Lynch Syndrome, Immunohistochemistry, IHC, DNA, HNPCC, Microsatellite Instability (MSI), Mismatch Repair Proteins, MMRP, hMLH-1, hMSH-2, hMSH-6, PMS2, Surgical and Histology.

Specimen Requirements

Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)		 Pediatric Minimum Volume
(no repeat)
Tissue 10% Neutral-Buffered Formalin (NBF) Fixed, Paraffin Embedded Tissue Block or Un-stained Slides  

5 mm

or

0.2 cm2

    

Acceptable Body Sites

Colorectal and endometrial tissue and its metastasis.  Carcinoma and non-neoplastic tissue required as non-neoplastic serves as a built-in control.

Acceptable Specimen Types

Paraffin embedded tissue specimens fixed in 10% NBF.         

  • One paraffin tissue block with corresponding H&E slide, or         
  • 4 unstained (3-4 microns), air-dried sections on charged slides and one H&E, or         
  • 5 unstained (3-4 microns), air-dried sections on charged slides.  

Fixatives other than 10% NBF have not been validated.

Collection/Processing Instructions

  1. Complete a Histology Requisition. Form must be compete and all slides/blocks labeled or testing will be delayed.  
  2. If applicable, include Surgical Pathology report containing pertinent patient history, tissue source, and diagnosis.

Specimen Stability Information

Specimen Type Temperature Time
Paraffin Embedded Tissue Block, Fixed in 10% NBF Ambient or Refrigerate Indefinite
3-4 Micron Unstained, Air-Dried, Charged Slides Ambient or Refrigerate 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 fresh.

Rejection Criteria

Unstained Slides not on charged slides

 

Insufficient data/Incomplete requisition

Test Components

hMLH-1, hMSH-2, hMSH-6, and PMS2

Test Information

Reason for Referral: Possible diagnosis of Lynch syndrome. Evaluate specimen for evidence of defective DNA mismatch repair protein expression.


IHC using monoclonal antibodies and a polymer detection system to determine the expression or absence thereof, for the following: hMLH-1, hMSH-2, hMSH-6, and PMS2. Lymphocytes and non-neoplastic epithelium exhibit strong nuclear staining to serve as a positive internal control.

 

Lynch Syndrome Testing Algorithm for Colorectal Carcinoma

 

Lynch Syndrome Testing Algorithm for Endometrial Carcinoma

Interferences

Tests have not been validated on fixatives other than 10% NBF.

 

Cut slides older than six weeks - False negatives may occur

 

Decalcified Tissue - False negatives may occur

Interpretations

This test is only available with interpretation.


The presence or absence of each marker serves as prognostic and predictive markers for the management of colonic or endometrial cancer.


Normal tissue is requested, as lymphocytes and non-neoplastic epithelium exhibit strong nuclear staining, which serves as a positive internal control for each protein.


Note: This DNA Mismatch Repair Protein panel is not a genetic test, but rather a screening tool for stratifying the risk of having an inherited cancer predisposition syndrome and identifies patients who may benefit from subsequent genetic testing.

Reference Range Information

Performing Location Reference Range
Marshfield

Interpretive Surgical Pathology Report 

This test is only available with interpretation.

 

All blocks and slides will be returned to the requestor, including controls if possible.  Each marker will be interpreted and resulted as Expressed, Absent, or Equivocal.  

 

Scoring References for Mismatch Repair Protein (MMRP) Expression by IHC:

  •  hMLH-1, HMSH-2, hMSH-6, and PMS2 Expressed = Preserved DNA Mismatch Repair Protein Expression.
  • hMLH-1, HMSH-2, hMSH-6, and/or PMS2 Absent = Loss of DNA Mismatch Repair Protein Expression  
  • hMLH-1, HMSH-2, hMSH-6, and/or PMS2 with Equivocal Expression = DNA Mismatch Repair Protein Expression Equivocal

Marshfield Labs Performing Department

Marshfield Labs Histology

Performing Information

Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
Histology Monday through Friday 2-3 days Polymer Based Detection System/Bond III

CPT Codes

CPT Modifier
(if needed)		 Quantity Description Comments
88342   1 DNA Mismatch Repair Proteins, hMLH-1, hMSH-2, hMSH-6, and PMS2, Paraffin Block by IHC. Used for the first IHC stain on a specimen
88341   3   Used for additional IHC stains on the same specimen.

Outreach CPT Codes

CPT Modifier
(if needed)		 Quantity Description Comments
88342   1 DNA Mismatch Repair Proteins, hMLH-1, hMSH-2, hMSH-6, and PMS2, Paraffin Block by IHC. Used for the first IHC stain on a specimen
88341   3   Used for additional IHC stains on the same specimen.