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MLH1 Mutation Analysis Test

Last updated July 26, 2019

Approved by: Maulik P. Purohit MD, MPH

The MLH1 Mutation Analysis Test is a genetic test that detects abnormalities in the MLH1 gene. It is used to diagnose cancer.

What are other Names for this Test? (Equivalent Terms)

  • COCA2 Mutation Analysis Test
  • HNPCC Mutation Analysis Test
  • MutL (E. coli) Homolog 1 (Colon Cancer, Nonpolyposis Type 2) Mutation Analysis Test

What is MLH1 Mutation Analysis Test? (Background Information)

  • MLH1 mutation refers to an alteration in the MLH1 gene, which is associated with colorectal, ovarian, stomach, small intestine, liver, urinary tract, and brain cancers
  • MLH1 mutation refers to an alteration in the MLH1 gene, which is associated with colorectal, ovarian, stomach, small intestine, liver, urinary tract, and brain cancers
    • DNA replication occurs just as a cell is preparing to divide. It must make a copy of its genetic material so that both daughter cells have one complete copy
    • However, the process is not foolproof; mutations occur (rarely) at a rate of 0.0000001, or 1 in 10 million base pairs that are copied
    • Although they occur rarely, because there are 3 billion base pairs that must be copied every time a cell divides, this error rate would amount to 300 mutations each time a cell divided
  • Luckily, repair proteins, such as MLH1, fix 99% of all errors or DNA replication, decreasing the error rate to a mere 1 in 10 billion
  • Abnormalities in the MLH1 gene may result in a defective MLH1 protein that is unable to repair DNA. This causes a host of ailments, the most significant of which is cancer
  • The MLH1 Mutation Analysis Test is a genetic test that detects abnormalities in the MLH1 gene. It is used to diagnose cancer. The test also aids in the treatment of cancer by guiding selection of therapeutic drugs, including disqualifying certain drugs from use

The molecular testing, in general, can be performed using a variety of methods. Some of these methods include:

  • In situ hybridization technique, such as fluorescence in situ hybridization (FISH)
  • Immunohistochemistry (IHC)
  • Next-generation sequencing (NGS)
  • Polymerase chain reaction (PCR)
  • Comparative genomic hybridization (CGH)
  • Karyotyping including spectral karyotyping
  • mRNA analysis
  • Tissue microarrays (TMAs)
  • Southern blot test
  • Northern blot test
  • Western blot test
  • Eastern blot test

The methodology used for the test may vary from one laboratory to another. 

Note: Molecular testing has limitations due to the molecular method and genetic mutational abnormalities being tested. This can affect the results on a case-by-case basis. Consultation with your healthcare provider will help in determining the right test and right molecular method, based on individual circumstances.

What are the Clinical Indications for performing the MLH1 Mutation Analysis Test?

The clinical indications for performing the MLH1 Mutation Analysis Test include:

  • Persistent abdominal bloating, indigestion or nausea
  • Changes in appetite, often a loss of appetite or feeling full sooner
  • Feelings of pressure in the pelvis or lower back
  • Needing to urinate more frequently
  • Changes in bowel movements
  • Increased abdominal girth
  • Feeling tired or low energy
  • Pelvic pain
  • Pain, shortly before or after beginning one’s period
  • Pressure, swelling, or pain in the abdomen
  • A dull ache in the lower back and thighs
  • Difficulty emptying your bladder
  • Pain during sex
  • Abnormal bleeding
  • Nausea or vomiting

In general, the molecular genetic testing is undertaken in the following situations:

  • To assist (and in some cases, confirm) the initial diagnosis
  • To distinguish other tumors/conditions that have similar histological features, when examined by a pathologist under the microscope
  • To help in determining treatment options
  • To confirm recurrence of the tumor: Tumor recurrence can either be at the original tumor site, or at a distant location (away from the initial site)

How is the Specimen Collected for MLH1 Mutation Analysis Test?

Following is the specimen collection process for MLH1 Mutation Analysis Test

The specimen sample requirements may vary from lab to lab. Hence, it is important to contact the testing lab for exact specimen requirements, before initiating the testing process.

  • Sample on which the test is performed may include:
    • Fresh tumor tissue during biopsy
    • Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumor
    • Unstained tissue slides
  • Process of obtaining the sample: As outlined by the laboratory testing facility
  • Preparation required: As outlined by the laboratory testing facility


  • In some cases, a different source of specimen (such as peripheral blood, bone marrow biopsy specimen, or other body fluids) may be acceptable to the laboratory performing the test
  • Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing
  • Depending on the location of testing, it may take up to 2 weeks’ turnaround time, to obtain the test results
  • Many hospitals preserve the paraffin blocks for at least 7 years. In general, older paraffin blocks (over 5 years) may affect the detection of specific mutations, due to degradation of the tumor specimen over time

Cost of MLH1 Mutation Analysis Test:

  • The cost of the test procedure depends on a variety of factors, such as the type of your health insurance, annual deductibles, co-pay requirements, out-of-network and in-network of your healthcare providers and healthcare facilities
  • In many cases, an estimate may be provided before the test is conducted. The final amount may depend upon the findings during the test procedure and post-operative care that is necessary (if any)

What is the Significance of the MLH1 Mutation Analysis Test Result?

A mutation in the MLH1 gene indicates a positive result for the MLH1 Mutation Analysis Test. This may point to a diagnosis of any of the following:

  • Gastrointestinal stromal tumor (GIST)
  • Lynch syndrome
  • Ovarian cancer
  • Colorectal cancer
  • Stomach cancer
  • Small intestine cancer
  • Liver cancer
  • Urinary tract cancer
  • Brain cancer

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.

Additional and Relevant Useful Information:

  • MLH1 mutation most notably occurs in a location of the chromosome called 3p22.2 - i.e., the short arm (p) of chromosome 3 in position 22.2
  • Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may perform this test

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider, the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

The following DoveMed website link is a useful resource for additional information:



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References and Information Sources used for the Article:

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Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 26, 2017
Last updated: July 26, 2019