Immunohistochemistry (IHC) for MMR and MSI

Immunohistochemistry (IHC) for MMR and MSI

This laboratory test is used mainly in patients with colorectal cancer to diagnose hereditary nonpolyposis colon cancer/LYNCH syndrome.

It is also done in some patients with sporadic (without family history) cancers of colon, rectum, uterine endometrium, stomach ,ovaries ,breast, prostate etc.

What is Lynch syndrome?

Lynch syndrome, also known as hereditary nonpolyposis colon cancer (HNPCC) syndrome, is due to inherited mutations in the mismatch repair genes. This syndrome makes a person more likely to get colorectal cancers at a younger age, as well increase the chances of developing other tumours such as endometrial carcinoma, tumours of the stomach, kidney, liver and brain. If any of your family members have a history of colon cancer, then there is a chance you may have Lynch syndrome.

What are MMR or mis-match repair genes?

Usually when the cell replicates, the process of MMR (mismatch repair) helps in repairing or fixing the errors (mutations) that happen when DNA (genetic material) copies itself. MMR or mismatch repair deficiency may happen in certain cells due to mutations in specific genes called MMR (mismatch repair ) genes. These genes are responsible for production of MMR proteins which correct the mistakes when DNA is copied in a cell. Due to deficiency of MMR proteins DNA mutation (change in DNA sequence) can happen which may cause various types of cancers. Lynch syndrome can happen due to mutation of MMR gene.

MSI (microsatellite instability) happens in these cancer cells due to MMR deficiency. It is a condition in which DNA becomes unstable. Thus a positive result is called microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR). A negative result is called microsatellite stable (MSS) or mismatch repair proficient (pMMR).

Why is MMR IHC test prescribed?

The health care provider may prescribe IHC for MMR test in patients with colorectal cancer to identify those with hereditary nonpolyposis colon cancer/Lynch syndrome. It helps to assess the prognosis of the cancer and decide the optimal treatment (chemotherapy) for that cancer.

What are the components of mismatch (MMR) Immunohistochemistry (IHC)?

This test includes:

• Testing for MLH1, MSH2, MSH6 and PMS2 proteins by the process of IHC (Immunohistochemistry)
• Reflex testing for MSI (microsatellite instability) by a process known as PCR (polymerase chain reaction).

Procedure and prerequisites

This test is done on tumour tissue usually obtained by a biopsy or after a resection surgery.

The tissue is processed and embedded in paraffin blocks and histopathological examination is done before being taken up for immunohistochemistry.

It is vital to submit relevant clinical history along with histopathology, cytopathology and radiological reports.