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HelpOrder Code BRMLH MLH1 Hypermethylation and BRAF Mutation Analysis, Tumor
Useful For
An adjunct to MSI / Microsatellite Instability (MSI), Tumor and IHC / Mismatch Repair (MMR) Protein Immunohistochemistry Only, Tumor testing, when colon tumor demonstrates microsatellite instability (MSI-H) and loss of MLH1 protein expression, to help distinguish a somatic versus germline event prior to performing expensive germline testing
An adjunct to negative MLH1 germline testing in cases where colon tumor from the same patient demonstrates MSI-H and loss of MLH1 protein expression
Genetics Test Information
If this test is ordered in conjunction with the MLH1 immunostain (IHC / Mismatch Repair [MMR] Protein Immunohistochemistry Only, Tumor) and MSI (MSI / Microsatellite Instability [MSI], Tumor), this test will only be performed when clinically indicated.
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| PBMLH | MLH1 Hypermethylation/BRAF Mutation | No | Yes |
Additional Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| SLIRV | Slide Review in MG | No, (Bill Only) | Yes |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| BMLHH | MLH1 Hypermethylation Analysis | Yes, (order ML1HM) | No |
| BBRAF | BRAF Analysis | Yes, (order BRAFD) | No |
Testing Algorithm
When this test is ordered, BRAF analysis and MLH1 hypermethylation analysis will always be performed. The exception would be if the tissue origin is an endometrial tumor; in those cases, only the MLH1 hypermethylation analysis component will be performed.
When this test is ordered, slide review will always be performed at an additional charge.
Special Instructions
Method Name
Methylation-Specific Polymerase Chain Reaction (PCR) and Digital Droplet Polymerase Chain Reaction (ddPCR)
Reporting Name
MLH1 Hypermethylation/BRAF MutationSpecimen Type
VariesOrdering Guidance
This test is not recommended as a first-tier screening for Lynch syndrome. Order TMSI / Microsatellite Instability, Tumor and IHC / Mismatch Repair (MMR) Protein Immunohistochemistry Only.
This test will only be performed on colon tumors demonstrating loss of MLH1 protein expression.
Necessary Information
Pathology report must accompany specimen in order for testing to be performed.
Specimen Required
Specimen Type: Tissue block or 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 both tumor and normal tissue.
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Frozen | |||
| Refrigerated | |||
Reject Due To
| Specimens that have been decalcified (all methods) Specimens that have not been formalin-fixed, paraffin-embedded Extracted DNA |
Reject |
Reference Values
An interpretive report will be provided.
Method Description
A methylation-specific polymerase chain reaction (PCR)-based assay is used to test tumor DNA for the presence of hypermethylation of the MLH1 promoter, based on a modification of the method described by Grady et al (Grady WM, Rajput A, Lutterbaugh JD, Markowitz S: Detection of aberrantly methylated hMLH1 promoter DNA in the serum of patients with microsatellite unstable colon cancer. Cancer Res 2001;61:900), and digital droplet PCR (ddPCR) is used to test for the presence of the V600E alteration within the BRAF gene.(Unpublished Mayo method)
Day(s) Performed
Varies
Performing Laboratory
Mayo Clinic Laboratories in Rochester
CPT Code Information
Slide Review
88381-Microdissection, manual
81210-BRAF (v-raf murine sarcoma viral oncogene homolog B1) (eg, colon cancer), gene analysis, V600E variant, if appropriate
81288-MLH1 promoter methylation analysis, if appropriate
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.