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HelpTest Code ML1HM MLH1 Hypermethylation Analysis, Tumor
Useful For
An adjunct to TMSI / Microsatellite Instability, Tumor and IHC / Mismatch Repair (MMR) Protein Immunohistochemistry Only, Tumor when colon or endometrial 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 or endometrial tumor demonstrates MSI-H and loss of MLH1 protein expression
Additional Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| SLIRV | Slide Review in MG | No, (Bill Only) | Yes |
Testing Algorithm
When this test is ordered, slide review will always be performed at an additional charge.
For more information see Lynch Syndrome Testing Algorithm.
Special Instructions
Method Name
Polymerase Chain Reaction (PCR)
Reporting Name
MLH1 Hypermethylation Analys, TumorSpecimen Type
VariesOrdering Guidance
This test is not recommended as a first-tier screening measure for hereditary nonpolyposis colon cancer. For more information see TMSI / Microsatellite Instability, Tumor and IHC / Mismatch Repair (MMR) Protein Immunohistochemistry Only, Tumor.
Testing will only be performed on colon or endometrial tumors demonstrating loss of MLH1 protein expression by immunohistochemistry.
Mayo Clinic's preferred screening test includes both MLH1 promoter hypermethylation and BRAF V600E testing. Order BRMLH / MLH1 Hypermethylation and BRAF Mutation Analysis, Tumor.
Extracted DNA from tissues is not an acceptable specimen type.
If the MMR immunohistochemistry (IHC) results for MLH1 and/or PMS2 suggest possible tumor heterogeneity, are ambiguous, or unusual, the physical IHC stains will be required to optimize the area of tissue selected for testing and for interpretation of the results. If IHC stains are required and not sent with the specimen, a request will be submitted to provide the IHC stains which will result in a slight delay.
Necessary Information
Pathology report and MMR IHC results 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 tumor tissue.
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Frozen | |||
| Refrigerated | |||
Reference Values
An interpretative report will be provided.
Interpretation
An interpretive report will be provided. The likelihood of a germline (inherited) mutation is very low in those cases where the tumor demonstrates MLH1 promoter hypermethylation and the normal tissue is unmethylated. The likelihood of a germline mutation is high in those cases where the tumor and normal tissue lack MLH1 promoter hypermethylation. In cases where the tumor and normal tissue demonstrate MLH1 promoter hypermethylation, this result will be interpreted as equivocal, and a blood sample will be requested to confirm potential germline hypermethylation.
Clinical Reference
1. 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 Oct;69(4):780-790
2. Wang L, Cunningham JM, Winters JL, et al: BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Cancer Res. 2003 Sep;63(17):5209-5212
3. Domingo E, Laiho P, Ollikainen M, et al: BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J Med Genet. 2004 Sep;41(9):664-668
4. Bettstetter M, Dechant S, Ruemmele P, et al: Distinction of hereditary nonpolyposis colorectal cancer and sporadic microsatellite-unstable colorectal cancer through quantification of MLH1 methylation by real-time PCR. Clin Cancer Res. 2007 Jun;13(11):3221-3228
5. Idos G, Valle L: Lynch syndrome. In: Adam MP, Mirzaa GM, Pagon RA, et al, eds. GeneReviews Internet). University of Washington, Seattle; 2004. Updated February 2, 2021. Accessed June 27, 2023. Available at www.ncbi.nlm.nih.gov/books/NBK1211/
Day(s) Performed
Varies
Report Available
7 to 14 daysPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
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
81288
88381
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| ML1HM | MLH1 Hypermethylation Analys, Tumor | 97761-1 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 53299 | Result Summary | 50397-9 |
| 53300 | Result | 82939-0 |
| 53301 | Interpretation | 69047-9 |
| 53302 | Reason for Referral | 42349-1 |
| 53303 | Specimen | 31208-2 |
| 53304 | Source | 85298-8 |
| 54447 | Tissue ID | 80398-1 |
| 53305 | Released By | 18771-6 |
Forms
1. Molecular Genetics: Inherited Cancer Syndromes Patient Information (T519)
2. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
-Gastroenterology and Hepatology Test Request (T728)
-Oncology Test Request (T729)
Specimen Minimum Volume
See Specimen Required