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25231 Lynch Syndrome DNA Mismatch Repair Proteins by IHC

Lynch Syndrome DNA Mismatch Repair Proteins by IHC
Test Code: HMISC
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.
Test Components
hMLH-1, hMSH-2, hMSH-6, and PMS2
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

Specimen Requirements
Fasting Required Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)		 Pediatric Minimum Volume
(no repeat)
​NO ​Tissue​ ​10% Neutral-Buffered Formalin (NBF) Fixed, Paraffin Embedded Tissue Block or Un-stained Slides ​ 5 mm or 0.2 cm2 ​ ​
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.​

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

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
Interpretation

​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.

Outreach CPTs
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.
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.
Test Components
hMLH-1, hMSH-2, hMSH-6, and PMS2
Ordering Applications
Ordering Application Description
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
Fasting Required Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)		 Pediatric Minimum Volume
(no repeat)
​NO ​Tissue​ ​10% Neutral-Buffered Formalin (NBF) Fixed, Paraffin Embedded Tissue Block or Un-stained Slides ​ 5 mm or 0.2 cm2 ​ ​
Collection Processing

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.​

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.
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
Interference
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
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

Test Components
hMLH-1, hMSH-2, hMSH-6, and PMS2
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
Interpretation

​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.

For more information visit:
Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
​Histology ​Monday through Friday ​2-3 days ​Polymer Based Detection System/Bond III
For billing questions, see Contacts
Outreach CPTs
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.
For most current information refer to the Marshfield Laboratory online reference manual.