• LDS
  • /Medical Tests
  • /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
0238U$ 0
81301$ 348.56

ICD10
C18Malignant neoplasm of colon
C18.0Malignant neoplasm of cecum
C18.1Malignant neoplasm of appendix
C18.2Malignant neoplasm of ascending colon
C18.3Malignant neoplasm of hepatic flexure
C18.4Malignant neoplasm of transverse colon
C18.5Malignant neoplasm of splenic flexure
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
C54Malignant neoplasm of corpus uteri
C54.1Malignant neoplasm of endometrium
C54.9Malignant neoplasm of corpus uteri, unspecified
C56Malignant neoplasm of ovary
C57Malignant neoplasm of other and unspecified female genital organs
C57.00Malignant neoplasm of unspecified fallopian tube
C57.01Malignant neoplasm of right fallopian tube
C57.02Malignant neoplasm of left fallopian tube
D12Benign neoplasm of colon, rectum, anus and anal canal
R97Abnormal tumor markers
R97.0Elevated carcinoembryonic antigen [CEA]
Z08Encounter for follow-up examination after completed treatment for malignant neoplasm
Z09Encounter for follow-up examination after completed treatment for conditions other than malignant neoplasm
Z15.09Genetic susceptibility to other malignant neoplasm
Z80.0Family history of malignant neoplasm of digestive organs
Z83.71Family history of colonic polyps
Z85Personal history of malignant neoplasm
Z85.0Personal history of malignant neoplasm of digestive organs
Z85.038Personal history of other malignant neoplasm of large intestine
Z85.048Personal history of other malignant neoplasm of rectum, rectosigmoid junction, and anus
Z85.05Personal history of malignant neoplasm of liver
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
Z86.004Personal history of in-situ neoplasm of other and unspecified digestive organs
Z86.010Personal history of colonic polyps
Z87.19Personal history of other diseases of the digestive system

Additional ICD10
C18.0Malignant neoplasm of cecum
C18.1Malignant neoplasm of appendix
C18.2Malignant neoplasm of ascending colon
C18.3Malignant neoplasm of hepatic flexure
C18.4Malignant neoplasm of transverse colon
C18.5Malignant neoplasm of splenic flexure
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
C54.0Malignant neoplasm of isthmus uteri
C54.1Malignant neoplasm of endometrium
C54.2Malignant neoplasm of myometrium
C54.3Malignant neoplasm of fundus uteri
C54.8Malignant neoplasm of overlapping sites of corpus uteri
C54.9Malignant neoplasm of corpus uteri, unspecified
C56.1Malignant neoplasm of right ovary
C56.2Malignant neoplasm of left ovary
C56.9Malignant neoplasm of unspecified ovary
C57.0Malignant neoplasm of fallopian tube
C57.00Malignant neoplasm of unspecified fallopian tube
C57.01Malignant neoplasm of right fallopian tube
C57.02Malignant neoplasm of left fallopian tube
C57.1Malignant neoplasm of broad ligament
C57.10Malignant neoplasm of unspecified broad ligament
C57.11Malignant neoplasm of right broad ligament
C57.12Malignant neoplasm of left broad ligament
C57.2Malignant neoplasm of round ligament
C57.20Malignant neoplasm of unspecified round ligament
C57.21Malignant neoplasm of right round ligament
C57.22Malignant neoplasm of left round ligament
C57.3Malignant neoplasm of parametrium
C57.4Malignant neoplasm of uterine adnexa, unspecified
C57.7Malignant neoplasm of other specified female genital organs
C57.8Malignant neoplasm of overlapping sites of female genital organs
C57.9Malignant neoplasm of female genital organ, unspecified
C7A.022Malignant carcinoid tumor of the ascending colon
C7A.023Malignant carcinoid tumor of the transverse colon
C7A.024Malignant carcinoid tumor of the descending colon
C7A.025Malignant carcinoid tumor of the sigmoid colon
D01.0Carcinoma in situ of colon
D12.0Benign neoplasm of cecum
D12.1Benign neoplasm of appendix
D12.2Benign neoplasm of ascending colon
D12.3Benign neoplasm of transverse colon
D12.4Benign neoplasm of descending colon
D12.5Benign neoplasm of sigmoid colon
D12.6Benign neoplasm of colon, unspecified
D12.7Benign neoplasm of rectosigmoid junction
D12.8Benign neoplasm of rectum
D12.9Benign neoplasm of anus and anal canal
D37.4Neoplasm of uncertain behavior of colon
D3A.022Benign carcinoid tumor of the ascending colon
D3A.023Benign carcinoid tumor of the transverse colon
D3A.024Benign carcinoid tumor of the descending colon
D3A.025Benign carcinoid tumor of the sigmoid colon
K63.5Polyp of colon
Z12.11Encounter for screening for malignant neoplasm of colon
Z83.71Family history of colonic polyps
Z85.0Personal history of malignant neoplasm of digestive organs
Z85.00Personal history of malignant neoplasm of unspecified digestive organ
Z85.01Personal history of malignant neoplasm of esophagus
Z85.02Personal history of malignant neoplasm of stomach
Z85.020Personal history of malignant carcinoid tumor of stomach
Z85.028Personal history of other malignant neoplasm of stomach
Z85.03Personal history of malignant neoplasm of large intestine
Z85.030Personal history of malignant carcinoid tumor of large intestine
Z85.038Personal history of other malignant neoplasm of large intestine
Z85.04Personal history of malignant neoplasm of rectum, rectosigmoid junction, and anus
Z85.040Personal history of malignant carcinoid tumor of rectum
Z85.048Personal history of other malignant neoplasm of rectum, rectosigmoid junction, and anus
Z85.05Personal history of malignant neoplasm of liver
Z85.06Personal history of malignant neoplasm of small intestine
Z85.060Personal history of malignant carcinoid tumor of small intestine
Z85.068Personal history of other malignant neoplasm of small intestine
Z85.07Personal history of malignant neoplasm of pancreas
Z85.09Personal history of malignant neoplasm of other digestive organs
Z85.1Personal history of malignant neoplasm of trachea, bronchus and lung
Z85.11Personal history of malignant neoplasm of bronchus and lung
Z85.110Personal history of malignant carcinoid tumor of bronchus and lung
Z85.118Personal history of other malignant neoplasm of bronchus and lung
Z85.12Personal history of malignant neoplasm of trachea
Z85.2Personal history of malignant neoplasm of other respiratory and intrathoracic organs
Z85.20Personal history of malignant neoplasm of unspecified respiratory organ
Z85.21Personal history of malignant neoplasm of larynx
Z85.22Personal history of malignant neoplasm of nasal cavities, middle ear, and accessory sinuses
Z85.23Personal history of malignant neoplasm of thymus
Z85.230Personal history of malignant carcinoid tumor of thymus
Z85.238Personal history of other malignant neoplasm of thymus
Z85.29Personal history of malignant neoplasm of other respiratory and intrathoracic organs
Z85.3Personal history of malignant neoplasm of breast
Z85.4Personal history of malignant neoplasm of genital organs
Z85.40Personal history of malignant neoplasm of unspecified female genital organ
Z85.41Personal history of malignant neoplasm of cervix uteri
Z85.42Personal history of malignant neoplasm of other parts of uterus
Z85.43Personal history of malignant neoplasm of ovary
Z85.44Personal history of malignant neoplasm of other female genital organs
Z85.45Personal history of malignant neoplasm of unspecified male genital organ
Z85.46Personal history of malignant neoplasm of prostate
Z85.47Personal history of malignant neoplasm of testis
Z85.48Personal history of malignant neoplasm of epididymis
Z85.49Personal history of malignant neoplasm of other male genital organs
Z85.5Personal history of malignant neoplasm of urinary tract
Z85.50Personal history of malignant neoplasm of unspecified urinary tract organ
Z85.51Personal history of malignant neoplasm of bladder
Z85.52Personal history of malignant neoplasm of kidney
Z85.520Personal history of malignant carcinoid tumor of kidney
Z85.528Personal history of other malignant neoplasm of kidney
Z85.53Personal history of malignant neoplasm of renal pelvis
Z85.54Personal history of malignant neoplasm of ureter
Z85.59Personal history of malignant neoplasm of other urinary tract organ
Z85.6Personal history of leukemia
Z85.7Personal history of other malignant neoplasms of lymphoid, hematopoietic and related tissues
Z85.71Personal history of Hodgkin lymphoma
Z85.72Personal history of non-Hodgkin lymphomas
Z85.79Personal history of other malignant neoplasms of lymphoid, hematopoietic and related tissues
Z85.8Personal history of malignant neoplasms of other organs and systems
Z85.81Personal history of malignant neoplasm of lip, oral cavity, and pharynx
Z85.810Personal history of malignant neoplasm of tongue
Z85.818Personal history of malignant neoplasm of other sites of lip, oral cavity, and pharynx
Z85.819Personal history of malignant neoplasm of unspecified site of lip, oral cavity, and pharynx
Z85.82Personal history of malignant neoplasm of skin
Z85.820Personal history of malignant melanoma of skin
Z85.821Personal history of Merkel cell carcinoma
Z85.828Personal history of other malignant neoplasm of skin
Z85.83Personal history of malignant neoplasm of bone and soft tissue
Z85.830Personal history of malignant neoplasm of bone
Z85.831Personal history of malignant neoplasm of soft tissue
Z85.84Personal history of malignant neoplasm of eye and nervous tissue
Z85.840Personal history of malignant neoplasm of eye
Z85.841Personal history of malignant neoplasm of brain
Z85.848Personal history of malignant neoplasm of other parts of nervous tissue
Z85.85Personal history of malignant neoplasm of endocrine glands
Z85.850Personal history of malignant neoplasm of thyroid
Z85.858Personal history of malignant neoplasm of other endocrine glands
Z85.89Personal history of malignant neoplasm of other organs and systems
Z85.9Personal history of malignant neoplasm, unspecified
Z86.010Personal history of colonic polyps

References