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MLH1 Promoter Hypermethylation

MLH1 promoter methylation, MSI, microsatellite instability, mismatch repair, MMR, sporadic MSI/MMR, Lynch Syndrome, colon cancer, MLHIG

Test Codes

EPIC: LAB3581

Department

Molecular Pathology

Specimen Collection Criteria

Collect: Paraffin-embedded tissue. A paraffin block must be submitted. (Slides or paraffin shavings are not acceptable.) Submit formalin-fixed, paraffin-embedded block with corresponding H&E slide. Tissue should be well fixed and well processed. Please submit the tissue block used for MMR testing if possible or otherwise the best tumor block or multiple blocks if the specimen is a small biopsy.

• The specimen must be accompanied by a completed requisition and must contain the patient name, date of birth, collection date, ordering physician, and source of specimen. 

Physician Office/Draw Specimen Preparation

Maintain paraffin-embedded tissue at room temperature (20-26°C or 68-78.8°F) until transport.

Preparation for Courier Transport

Transport: Paraffin-embedded tissue, at room temperature (20-26°C or 68-78.8°F).

Rejection Criteria

• Tissue decalcified with agents other than Mol Decal (EDTA).
• Fixatives other than 10% neutral buffered formalin.
• Specimens fixed/processed in alternative fixatives (e.g., alcohol, zinc formalin).
• Improper labeling or inadequate information. 
• Inadequate tumor cellularity, at discretion of medical director.
• Poor quality and/or quantity of extracted genomic DNA.

Testing will be cancelled on specimens meeting the above criteria with client notification.

Inpatient Specimen Preparation

Specimens at Royal Oak may be sent to the Surgical Pathology tube station, #201. In-house specimens are also picked up by a Surgical Pathology assistant every hour on the hour.

In-Lab Processing

Maintain specimens at room temperature (20-26°C or 68-78.8°F) until testing.

Storage

Specimen Stability for Testing:

Room Temperature (20-26°C or 68-78.8°F): Indefinitely

Specimen Storage in Department Prior to Disposal:

Residual tissue blocks are returned to the storage facility of origin when testing is complete.

Specimen Storage (DNA libraries post testing):

Frozen (-25° to -15°C): 2 months

Laboratory

Royal Oak Molecular Pathology Laboratory

Performed

Monday – Friday.
Results available in 7-10 business days.

Reference Range

MLH-1 promoter is not methylated.

Test Methodology

Following DNA extraction and bisulfite treatment, molecular analysis of the promoter region of the MLH-1 gene is performed by methylation-specific qualitative real-time PCR.

Interpretation

MLH-1 promoter is not methylated.
MLH-1 promoter is methylated.

Clinical Utility

This test is intended for use only in tumors that have loss of MLH1 expression by mismatch repair immunohistochemistry (MMR IHC). MMR IHC reflex testing is performed in all in-house colorectal and endometrial carcinoma resection specimens to screen for Lynch syndrome.  Any such tumors which show loss of MLH1 expression will receive MLH1 promoter methylation testing.  This test can also be ordered upon clinician request in other situations for tumors that show loss of MLH1 expression by MMR IHC.

For colorectal and endometrial cancers that demonstrate loss of MLH1 expression by MMR IHC, methylation of the MLH-1 gene promoter is consistent with somatic alteration of the MLH1 gene, rather than a germline mutation of MLH1 (i.e., Lynch Syndrome).

CPT Codes

81288

Contacts

Last Updated

10/6/2025