MLH1 Promoter Hypermethylation

General Information

Lab Name

Lab Code

MLH1MT

Epic Name

Order using "UW Genetics and Solid Tumor Test Request" See tip sheet for more information (internal link).

Description

MLH1 promoter methylation assay is useful for the evaluation of hereditary colorectal cancer and tumors that have MLH1 and PMS2 loss by immunohistochemistry (IHC). Approximately 85% of tumors that have IHC loss of MLH1 and PMS2 will have MLH1 promoter methylation, the majority of which is somatic in origin. The remaining tumors with IHC loss of MLH1 and PMS2 will have somatic or germline mutations in MLH1. Individuals with germline mutations in MLH1 have an increased risk for cancer associated with Lynch syndrome. When methylation is negative, molecular MLH1 testing of germline and/or tumor is recommended to determine the cause of the MLH1 and PMS2 loss and whether a patient has Lynch syndrome.

Forms & Requisitions

Providers with access to the UW implementation of Epic (i.e., FHCC, HMC, SCCA, UWMC, UWNW) may order this test using the order "UW Genetics and Solid Tumor Test Request." See tip sheet for more information (internal link).

Synonyms

Colorectal cancer, endometrial cancer, Gynecological Oncology Pathway, GYNPTH

Components

Code	Name
M1MTCH	MLH1 Methylation Clinical History
M1MTRE	MLH1 Methylation Result
M1MTIN	MLH1 Methylation Interpretation
M1MTMT	MLH1 Methylation Method
M1MTDI	MLH1 Methylation Director

Interpretation

Guidelines

Method

Tumor DNA is bisulfite converted and amplified with a PCR-based assay to assess MLH1 promoter hypermethylation

Reference Range

See individual components

Ordering & Collection

Specimen Type: Formalin Fixed Paraffin Embedded tissue or whole blood
Collection: EITHER (a) slides OR (b) tissue block OR (c) blood:

(a) Instructions for slide specimens: 1 slide at 4-micron thickness stained with hematoxylin-and-eosin AND 10 unstained, non-baked slides at 10-micron thickness (a minimum of 5 unstained slides is acceptable). Unstained slides can be on charged or uncharged slides.

Note: sections should contain as much tumor as possible.

(b) Instructions for tissue block specimen: Provide complete tissue block containing tumor tissue. If there is more than one tissue block, please provide the block that has the greatest amount of tumor tissue. Tissue block will be returned at completion of testing.

(c) Instruction for blood specimens: Normal tissue or blood can be submitted for evaluation of constitutional MLH1 promoter hypermethylation
• 10 mL whole blood in LAVENDER TOP EDTA tube.
• Also acceptable: YELLOW TOP ACD tube, purified DNA from peripheral blood or cultured cells

(d) Add-on after prior testing in our lab: contact Genetics lab

Unacceptable: Decalcified sample
Forms & Requisitions: Providers with access to the UW implementation of Epic (i.e., FHCC, HMC, SCCA, UWMC, UWNW) may order this test using the order "UW Genetics and Solid Tumor Test Request." See tip sheet for more information (internal link).
Handling Instructions: Attach a copy of the pathology report for the tumor sample being submitted.

Outside Laboratories: Ship at room temperature.
Quantity: Requested: Slides or tissue block or blood as noted above.
Minimum: 5 unstained slides (10-micron thickness) with 20% tumor nuclei or 5mL peripheral blood

Processing

Receiving Instructions: Hold slides or tissue blocks at room temperature.

Outside Laboratories: Ship at room temperature.

Misc Sendout

Performance

Lab Department

Genetics(GEN)

Frequency

Run at least once a week; Typical Turnaround: 3 weeks *Turn around times may vary based on factors such as tissue acquisition and insurance preauthorization.

Available STAT?

Performing Location(s)

UW-MT	Genetics Attention: Genetics Lab Clinical lab, Room NW220 University of Washington Medical Center 1959 NE Pacific Street Seattle, WA 98195 Tel: 206-598–6429 M–F (7:30 AM–4:00 PM) Fax: 206-616-4584 Lab email: cgateam@uw.edu Tel (EXOME only): 206-543-0459	Faculty Jillian Buchan, PhD, FACMG Runjun Kumar, MD, PhD Regina Kwon, MD, MPH Christina Lockwood, PhD, DABCC, DABMGG Abbye McEwen, MD, PhD Colin Pritchard, MD, PhD Vera Paulson, MD, PhD Eric Konnick, MD, MS He Fang, PhD

Billing & Coding

CPT Codes: 81288
LOINC: 58416-9
Interfaced Order Code: UOW5678