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- MLH1 promoter hypermethylation
Special Instructions
Please provide a copy of the pathology report. MLH1 testing will be delayed if the pathology report is not received. Please direct any questions regarding this test to customer service at 800-345-4363.
Expected Turnaround Time
6 - 10 days
Turnaround time is defined as the usual number of days from the date of pickup of a specimen for testing to when the result is released to the ordering provider. In some cases, additional time should be allowed for additional confirmatory or additional reflex tests. Testing schedules may vary.
Related Information
Related Documents
Specimen Requirements
Specimen
Formalin-fixed, paraffin-embedded (FFPE) tissue block or slides
Volume
8 pre-cut unstained slides at 5 micron with 1 matching H&E reference slide, or FFPE tissue block
Minimum Volume
Tumor surface area ≥4mm2 tumor area and ≥ 50% tumor content are preferred.
Container
Tissue block and slide container
Storage Instructions
Room temperature
Causes for Rejection
No tumor tissue in FFPE blocks or slides; broken or stained slides
Test Details
Use
Hereditary colon cancers of the nonpolyposis type (HNPCC) or Lynch Syndrome (LS) is an inherited cancer syndrome caused by a germline mutation in one of several genes involved in DNA mismatch repair (MMR), including MLH1, MSH2, MSH6 and PMS2, or EPCAM gene. It is estimated to account for 1-3% of colorectal cancer (CRC). Although HNPCC is characterized by abnormal immunohistochemistry for MMR proteins and microsatellite instability (MSI-H), cancers exhibiting abnormal IHC for MLH1 and are MSI-H are most often sporadic (non-inherited) and due to abnormal methylation of the MLH1 gene promoter. Tumors that have the BRAF V600E mutation and MLH1 promoter hypermethylation are almost certainly sporadic, whereas tumors that show neither are most often caused by an inherited mutation. Testing for methylation of the MLH1 promoter can help distinguish sporadic from inherited cancers.
Limitations
In vitro studies indicate that this assay has a sensitivity to detect approximately 1-5% methylated MLH1 promoter.
This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA).
Methodology
Bisulfite converstion, methylation-specific PCR, and gel electrophoresis
References
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. ClinCancer Res. 2007 June 1;13(11):3221-3228.17545526
Kuismanen SA, Holmberg MT, Salovaara R, de la Chapelle A, Peltomaki P. Genetic and epigenetic modification of MLH1 accounts for a major share of microsatellite-unstable colorectal cancers. Am J Pathol. 2000 May;156(5):1773-1779.10793088
NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Colorectal. Version 3. October 10, 2017.
Stoffel EM, Mangu PB, Gruber SB, et al. Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines. J Clin Oncol. 2015 Jan 10;33(2):209-217.25452455
LOINC® Map
| Order Code | Order Code Name | Order Loinc | Result Code | Result Code Name | UofM | Result LOINC |
|---|---|---|---|---|---|---|
| 512031 | MLH1 Methylation Analysis | 58416-9 | 512032 | MLH1 Result | 58416-9 | |
| 512031 | MLH1 Methylation Analysis | 58416-9 | 512033 | Indication | 42349-1 | |
| 512031 | MLH1 Methylation Analysis | 58416-9 | 512034 | Location | N/A | |
| 512031 | MLH1 Methylation Analysis | 58416-9 | 512035 | Specimen Type | 31208-2 | |
| 512031 | MLH1 Methylation Analysis | 58416-9 | 512036 | Block ID | 57723-9 | |
| 512031 | MLH1 Methylation Analysis | 58416-9 | 512037 | Background | 8251-1 | |
| 512031 | MLH1 Methylation Analysis | 58416-9 | 512039 | Method | 49549-9 | |
| 512031 | MLH1 Methylation Analysis | 58416-9 | 512040 | References | 75608-0 | |
| 512031 | MLH1 Methylation Analysis | 58416-9 | 512041 | Director Review | 72486-4 | |
| 512031 | MLH1 Methylation Analysis | 58416-9 | 480903 | Microdissection Performed | 8100-0 |
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