Diseases (19)
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$584.9
81301$348.56
81457$0
81458$0
81463$0

ICD10
ICD CODE AND DESCRIPTIONLCD CODENCD CODE
C15 - Malignant neoplasm of esophagus
C16 - Malignant neoplasm of stomach
C17 - Malignant neoplasm of small intestine
C17.0 - Malignant neoplasm of duodenum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C17.1 - Malignant neoplasm of jejunum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C17.2 - Malignant neoplasm of ileum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C17.9 - Malignant neoplasm of small intestine, unspecified56867, 57905, 57858, 57831, 57901, 57450, 59609, 56199, 52986
C18 - Malignant neoplasm of colon
C18.0 - Malignant neoplasm of cecum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.1 - Malignant neoplasm of appendix56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.2 - Malignant neoplasm of ascending colon56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.3 - Malignant neoplasm of hepatic flexure56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.4 - Malignant neoplasm of transverse colon56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.5 - Malignant neoplasm of splenic flexure56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.6 - Malignant neoplasm of descending colon56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.7 - Malignant neoplasm of sigmoid colon56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.8 - Malignant neoplasm of overlapping sites of colon56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.9 - Malignant neoplasm of colon, unspecified56867, 57905, 57858, 57831, 57901, 57450, 59609, 56199, 52986
C19 - Malignant neoplasm of rectosigmoid junction56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C20 - Malignant neoplasm of rectum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C21 - Malignant neoplasm of anus and anal canal
C21.0 - Malignant neoplasm of anus, unspecified56867, 57905, 57858, 57831, 57870, 57901, 52986
C21.1 - Malignant neoplasm of anal canal56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 59609, 56199, 52986
C21.8 - Malignant neoplasm of overlapping sites of rectum, anus and anal canal56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C38 - Malignant neoplasm of heart, mediastinum and pleura
C38.0 - Malignant neoplasm of heart56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C38.1 - Malignant neoplasm of anterior mediastinum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C38.2 - Malignant neoplasm of posterior mediastinum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C38.3 - Malignant neoplasm of mediastinum, part unspecified56867, 57905, 57858, 57831, 57901
C38.4 - Malignant neoplasm of pleura56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 52986
C38.8 - Malignant neoplasm of overlapping sites of heart, mediastinum and pleura56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C39 - Malignant neoplasm of other and ill-defined sites in the respiratory system and intrathoracic organs
C39.0 - Malignant neoplasm of upper respiratory tract, part unspecified56867, 57905, 57858, 57831, 57870, 57901
C43.52 - Malignant melanoma of skin of breast56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 59609, 56199, 52986
C44 - Other and unspecified malignant neoplasm of skin
C45 - Mesothelioma
C45.0 - Mesothelioma of pleura56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 52986
C45.1 - Mesothelioma of peritoneum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 52986
C45.2 - Mesothelioma of pericardium56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C45.7 - Mesothelioma of other sites56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C45.9 - Mesothelioma, unspecified56867, 57905, 57858, 57831, 57901, 52986
C48 - Malignant neoplasm of retroperitoneum and peritoneum
C48.0 - Malignant neoplasm of retroperitoneum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 52986
C48.1 - Malignant neoplasm of specified parts of peritoneum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 59609, 56199, 52986
C48.2 - Malignant neoplasm of peritoneum, unspecified56867, 57905, 57858, 57831, 57901, 52986
C48.8 - Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 52986
C49 - Malignant neoplasm of other connective and soft tissue
C49.8 - Malignant neoplasm of overlapping sites of connective and soft tissue56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C49.9 - Malignant neoplasm of connective and soft tissue, unspecified56867, 57905, 57858, 57831, 57901, 52986
C49.A - Gastrointestinal stromal tumor

Additional ICD10
ICD CODE AND DESCRIPTIONLCD CODENCD CODE
C15.3 - Malignant neoplasm of upper third of esophagus56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C15.4 - Malignant neoplasm of middle third of esophagus56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C15.5 - Malignant neoplasm of lower third of esophagus56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C15.8 - Malignant neoplasm of overlapping sites of esophagus56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C15.9 - Malignant neoplasm of esophagus, unspecified56867, 57905, 57858, 57831, 57901
C16.0 - Malignant neoplasm of cardia56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450
C16.1 - Malignant neoplasm of fundus of stomach56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450
C16.2 - Malignant neoplasm of body of stomach56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450
C16.3 - Malignant neoplasm of pyloric antrum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450
C16.4 - Malignant neoplasm of pylorus56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450
C16.5 - Malignant neoplasm of lesser curvature of stomach, unspecified56867, 57905, 57858, 57831, 57870, 57901, 57450
C16.6 - Malignant neoplasm of greater curvature of stomach, unspecified56867, 57905, 57858, 57831, 57870, 57901, 57450
C16.8 - Malignant neoplasm of overlapping sites of stomach56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450
C16.9 - Malignant neoplasm of stomach, unspecified56867, 57905, 57858, 57831, 57901, 57450
C17.0 - Malignant neoplasm of duodenum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C17.1 - Malignant neoplasm of jejunum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C17.2 - Malignant neoplasm of ileum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C17.3 - Meckel's diverticulum, malignant56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C17.8 - Malignant neoplasm of overlapping sites of small intestine56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C17.9 - Malignant neoplasm of small intestine, unspecified56867, 57905, 57858, 57831, 57901, 57450, 59609, 56199, 52986
C18.0 - Malignant neoplasm of cecum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.1 - Malignant neoplasm of appendix56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.2 - Malignant neoplasm of ascending colon56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.3 - Malignant neoplasm of hepatic flexure56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.4 - Malignant neoplasm of transverse colon56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.5 - Malignant neoplasm of splenic flexure56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.6 - Malignant neoplasm of descending colon56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.7 - Malignant neoplasm of sigmoid colon56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.8 - Malignant neoplasm of overlapping sites of colon56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C18.9 - Malignant neoplasm of colon, unspecified56867, 57905, 57858, 57831, 57901, 57450, 59609, 56199, 52986
C21.0 - Malignant neoplasm of anus, unspecified56867, 57905, 57858, 57831, 57870, 57901, 52986
C21.1 - Malignant neoplasm of anal canal56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 59609, 56199, 52986
C21.2 - Malignant neoplasm of cloacogenic zone56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C21.8 - Malignant neoplasm of overlapping sites of rectum, anus and anal canal56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 57450, 59609, 56199, 52986
C38.0 - Malignant neoplasm of heart56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C38.1 - Malignant neoplasm of anterior mediastinum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C38.2 - Malignant neoplasm of posterior mediastinum56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C38.3 - Malignant neoplasm of mediastinum, part unspecified56867, 57905, 57858, 57831, 57901
C38.4 - Malignant neoplasm of pleura56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491, 52986
C38.8 - Malignant neoplasm of overlapping sites of heart, mediastinum and pleura56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C39.0 - Malignant neoplasm of upper respiratory tract, part unspecified56867, 57905, 57858, 57831, 57870, 57901
C39.9 - Malignant neoplasm of lower respiratory tract, part unspecified56867, 57905, 57858, 57831, 57870, 57901
C44.0 - Other and unspecified malignant neoplasm of skin of lip
C44.00 - Unspecified malignant neoplasm of skin of lip56867, 57905, 57858, 57831, 57870, 57901
C44.01 - Basal cell carcinoma of skin of lip56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C44.02 - Squamous cell carcinoma of skin of lip56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C44.09 - Other specified malignant neoplasm of skin of lip56867, 57905, 57858, 57831, 57870, 57901, 59492, 59123, 59125, 59491
C44.1 - Other and unspecified malignant neoplasm of skin of eyelid, including canthus
C44.10 - Unspecified malignant neoplasm of skin of eyelid, including canthus
C44.101 - Unspecified malignant neoplasm of skin of unspecified eyelid, including canthus56867, 57905, 57858, 57831, 57870, 57901

References