L.E.M laboratory provides MSI test (including IHC) for private and national health caretakers.

Results given in 7-14 days only!

For more information call Tel.08-9380770, Fax.08-9389783, E-mail: admin@lem-lab.com

MSI- Micro Satellite Instability test is performed with IHC- Immunohistochemical staining in order to measure malfunctions in the DNA Mismatch Repair Mechanism (MMR).

Recently, the FDA has approved using the immune therapy medicine "Keytruda" according to these indicators. Moreover, it can be used regardless to the location of the tumor in the patient's body. Until now, MSI test was limited to diagnosing Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer- HNPCC).

Keytruda (generic name: Pembrolizumab) is included in the israeli medical health "basket", press here for more info (hebrew)!

The importance of MSI test goes two ways. First, helping the oncologist decide upon the specific and most effective treatment for the cancer patient, including using immunotherapy for those who can benefit from it. Secondly, if the cancer is hereditary, as seen in the MSI test, it is important for family members to be checked and attend an early detection routine in order to prevent development of cancer.

What is a MSI test?

MSI- Micro Satellite instability- are recurring DNA sequences that are not translated into proteins. When there is a problem with the MMR (Mismatch Repair Mechanism) these sequences undergo mutations in a high frequency, and their length changes. MSI test is performed on tissue from the tumor as well as on a healthy tissue, and traces this phenotype.

MSI test has 2 major indications:

The new indication-

Testing for a possibility to treat PD-L1 inhibitors and in particular Pembrolizumab (Keytruda), based on findings showing that a high percentage of patients suffering from metastatic colon cancer tend to respond well to the immunotherapy treatment.

The common indication-

When there is a suspicion for HNPCC (lynch syndrome). HNPCC causes 3-5% of all colon cancer and 20-35% of familial colon malignancies.

Lynch syndrome is linked to increased risk of bowel cancer (up to 80% during life span) and uterus cancer (20-60% during life span). In addition, it is linked to higher risk of other malignancies, as specially cancer of the ovary (13%), urinary system (5-8%), malignancies of the upper digestive system and the brain. Age of average morbidity is lower for HNPCC, 44 years old as opposed to 64 years for sporadic bowel cancer.

Histopathological characteristics of HNPCC malignancies tend to differ from other malignancies. For instance, HPNCC bowel malignancies appear more on the right bowel, and tend to show more mucus cells and eminent inflammatory infiltrates.

HPNCC syndrome is inherited by dominate autosome. It is caused by mutations in one of the MMR. In 90-95% of HPNCC malignancies the malignant tissue is characterized with High Microsatellite instability (H-MSI).

How is MSI test performed in L.E.M lab?

MSI test is done on tumor tissue as well as on healthy tissue using "MSI Analysis System Version 1.2" by Promega corporation.

The kit is used regularly in all major institutes performing MSI tests, amongst them Shaare zedek medical center, Tel Aviv Sourasky medical center, Rabin medical center (Beilinson), Maccabi "Mega lab" and more. 

5 mononucleotide markers are tested (BAT-25, BAT-26, NR-21, NR-24 , MONO-27) and 2 pentanucleotides (penta D and penta C).

Possible results are MSI-High, MSI-Low, MSI- Stable (MSS).

IHC stains for MMR:

MSI test results are given with IHC results.

IHC of the malignant tissue with specific antibodies in order to identify proteins coded by MMR genes (PMS2, MSH6, MSH2, MLH1) enables identification of these genes thus finding the suspected gene that has undergone mutation.

In most cases there is a high correlation between IHC results, and MSI test results.

IHC is done using reagents and antibodies produced by Roche-Ventana.

Control tissue is from the colon. Staining protocol by company requirements.

In order to perform MSI test and IHC in L.E.M please provide:

- Tissue from tumor

- Healthy tissue

- Pathology report.


References

1.    Lynch HT, de la Chapelle A, Hereditary colorectal cancer. N Engl J Med. 2003 March.

2.    Funaioli C, Pinto CMutri V et al. Does biomolecular characterization of stage II/III colorectal cancer have any prognostic value? Clin Colorectal Cancer. 2006 May;6(1):38-45.

3.     D.T. Le, J.N. Uram, Diaz, Jr et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015;372:2509-20.