• Test Code:
    2027
  • Department:
    Molecular Genetics
  • Test Synonyms:
    MLH1 methylation • promoter methylation • MLH1
  • CPT Code(s):
    81288
Background:

Approximately 15% of colorectal tumors which display microsatellite instability (MSI) are due to hereditary causes such as Lynch syndrome (HNPCC). MLH1 promoter methylation and gene silencing is the primary cause of microsatellite instability in sporatic endometrial cancers. More commonly, MSI is a result of somatic MLH1 promoter hypermethylation1.

Immunohistochemistry would likely reveal a lack of MLH1 protein in this case or in the case of a germ line mutation in MLH1. In an effort to differentiate between hereditary and somatic causes of MSI related to MLH1, the methylation status of the MLH1 promoter can be ascertained; if hyper-methylated, then the cause is likely not due to a hereditary mutation.

Reasons for Referral:
Determination of hereditary vs. sporadic cause of colorectal cancer for all colorectal endometrial cancer patients with tumor tissue demonstrating microsatellite instability (MSI-H) and loss of MLH1 protein.

Methodology:

Multiplex Ligation Probe Amplification (MLPA) using methylation sensitive restriction enzymes is used to identify methylation status of the MLH1 promoter region.

Specimen Requirements:

Preferred:

  • 1 paraffin tissue block of tumor with minimal normal tissue.

If tissue blocks cannot be sent:

  • 5 unstained slides of tumor at 7 micron, and 1 H&E slide.

If sending DNA: please send 200ng at a minimum of 10ng/µL (DNA must be extracted in a CLIA certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS).

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

14-21 days

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cool, but not frozen.
  • Ship via overnight express, using the FedEx priority overnight label provided.
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

  1. Perez-Carbonell, L. et al. (2010) Journal of Mol. Diagnostics 12(4): 498-504.
  2. Fleisher, A. et al. (1999) Cancer Research 59: 1090-1095.

Additional Info:

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