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  • /Microsatellite Instability (MSI), HNPCC/Lynch Syndrome, by PCR

Diseases (6)

Diagnostic Testing (5)

Note:

The sensitivity of microsatellite instability (MSI) testing for Lynch Syndrome is about 85-95%.


Note:

Differential diagnosis of hereditary nonpolyposis type colon cancer (HNPCC)


Note:

Differential diagnosis of hereditary nonpolyposis type colon cancer (HNPCC)


Note:

Differential diagnosis of hereditary nonpolyposis type colon cancer (HNPCC)

Disease Management Testing (1)

Note:

Useful as screen for Lynch Syndrome if endometrial carcinoma has been diagnosed.

Overview

Microsatellite instability is used as an aid in the diagnosis of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) also know as Lynch syndrome. Microsatellites are also known as short tandem repeats found in human DNA as a regulatory and structural part of the human genome. These microsatellites are not longer than 2-6 base pairs in length found in 10-50 repeats. The regions of microsatellite instability are susceptible to mistakes during DNA replication that are typically repaired by mismatch repair proteins (MMR).

Mutation in MMR genes results in nonfunctional MMR proteins, which often results in accumulation of non-repaired, damaged mutated short tandem repeats leading to microsatellite instability (MSI). There are several MMR genes that are prone to mutations. The most common MMR are hMLH1, hMSH2, hPMS1, and hPMS2. Mutations on any of these genes or more than one gene can lead to MSI.

MSI is predominantly associated with polyposis and nonpolyposis colorectal cancer, especially with HNPCC. Hereditary nonpolyposis colorectal cancer (HNPCC) can be a component of Lynch syndrome. It is an autosomal dominant syndrome with early onset of colonic carcinoma and with increased risk for malignancy. Genetic testing for MMRs can confirm the diagnosis of HPNCC and can also identify presymptomatic individuals at risk among the patient's relatives. This test usually covers most common gene mutations (coding regions) in hMLH1, hMSH2, hPMS1, and hPMS2. Early screening can help in patients with family history of colorectal cancer.

Clinical Utility

  • In evaluation for hereditary nonpolyposis type colon cancer (HNPCC)
  • Screening for MSI or MMR gene mutation in patients with family history of colon cancer
  • Differential diagnosis of colon cancer type
  • Therapy and disease management
  • Evaluation of family members
  • Guiding preventative measures

Interpretation

Mutations of genes in hMLH1, hMSH2, hPMS1, and hPMS2 (one or more) are present in individuals with HNPCC
>30-40% : MSI-H phenotype

Increased in:

  • Colorectal cancer, some
  • Endometrial cancer, some
  • Ovarian Cancer, some
  • Stomach Cancer, some

Decreased in:

  • Tumors associated with MSH6 mutations.

Reference Ranges

Negative for mutations analyzed
 

 

 

Methodology

Real Time PCR, PCR with Allele Specific Primer Extension, Pyrosequencing, Chip array, Immunohistochemistry, FISH.

Specimen Collection

Tissue & Whole Bood EDTA (Lavender) or ACD (Yellow)

Stability:

  • Ambient: 8 days
  • Refrigerated: 8 days

Additional Testing

Carcinoembryonic Antigen (CEA), Chromosomal analysis, Occult blood, B-RAF mutation analysis, Microsatellite Instability/HNPCC by molecular method and by IHC, Septin 9 (SEPT9), K-RAS, EGFR Mutation Detection by molecular method, p53 by molecular method and by IHC, Ki67 by IHC, p63 by IHC.

Turnaround Time

10-13 days.

CPT

81301

LOINC

ICD10

C18Malignant neoplasm of colon
C18.0Malignant neoplasm of cecum
C18.2Malignant neoplasm of ascending colon
C18.4Malignant neoplasm of transverse colon
C18.6Malignant neoplasm of descending colon
C18.7Malignant neoplasm of sigmoid colon
C18.8Malignant neoplasm of overlapping sites of colon
C18.9Malignant neoplasm of colon, unspecified
C19Malignant neoplasm of rectosigmoid junction
C20Malignant neoplasm of rectum
C54.1Malignant neoplasm of endometrium
C54.9Malignant neoplasm of corpus uteri, unspecified
C56Malignant neoplasm of ovary
C57.00Malignant neoplasm of unspecified fallopian tube
C57.01Malignant neoplasm of right fallopian tube
C57.02Malignant neoplasm of left fallopian tube
R97Abnormal tumor markers
R97.0Elevated carcinoembryonic antigen [CEA]
Z80.0Family history of malignant neoplasm of digestive organs
Z85Personal history of malignant neoplasm
Z85.0Personal history of malignant neoplasm of digestive organs
Z85.42Personal history of malignant neoplasm of other parts of uterus
Z85.44Personal history of malignant neoplasm of other female genital organs
Z85.9Personal history of malignant neoplasm, unspecified

References