Microsatellite Instability in Colorectal Cancer

Introduction

Microsatellite instability refers to a genetic alteration observed in specific cells, such as cancer cells, where the number of repeated DNA bases in a short, repetitive DNA sequence called a microsatellite differs from the original inherited number. Microsatellite instability can arise from uncorrected errors during DNA replication in a cell. It is predominantly detected in colorectal cancer, gastric cancer, and endometrial cancer, although it can also be present in numerous other cancer types. Determining the presence of microsatellite instability in a malignancy can aid in devising the most effective treatment strategy. MSI is an abbreviation for Microsatellite instability.

What Are Microsatellites?

The care team may discuss microsatellite instability (MSI), an associated disease complication in specific cancer types. Microsatellites are brief segments of DNA, the genetic material responsible for carrying the code. They generally comprise one to six base pairs that exhibit multiple repetitions.

What Is Colorectal Cancer?

Colorectal cancer originates in either the colon or the rectum. These malignancies may also be referred to as colorectal cancer, with the specific terminology depending on the site of origin. Colon cancer and rectal cancer are frequently classified together due to their shared characteristics.

What Is Microsatellite Instability?

Unstable microsatellites do exist. Microsatellite instability transpires when the DNA patterns of the microsatellite discovered within a malignant tumor undergo a modification that deviates from its hereditary state.

• Certain forms of malignancy exhibit elevated MSI values due to their substantial number of DNA mutations. This results in the cells' inability to repair themselves properly, which may promote the rapid growth of tumor cells.

• MSI is significant because it can aid physicians in determining the optimal cancer treatment for a patient.

• The instability of microsatellites is most frequently observed in colorectal, endometrial, and gastric malignancies.

What Is the Role of Immunotherapy in Cancer?

Immunotherapy is a medical treatment for cancer that enhances the body's immune system via medicine, enabling it to more effectively recognize and eliminate cancer cells. Immune checkpoint inhibitors are a frequently utilized kind of immunotherapy.

Immune checkpoints are inherent mechanisms of the body's immune system. T-cells, a subset of immune cells, occasionally interact with a protein in cancerous tumor cells. This protein is known as an immunological checkpoint protein. When these specific types of cells come into contact, it can potentially suppress the immune system's reaction, preventing it from eliminating the tumor cells. Immune checkpoint inhibitor therapy deactivates this checkpoint, allowing the immune system to eliminate cancer cells.

Microsatellite instability can affect the response of some tumors to immunotherapy. Here is the essential information that patients and their families should be aware of about microsatellite instability.

What Is MSI Testing?

MSI testing may be advised for patients with malignancies known to exhibit microsatellite instability. This may aid in predicting which cancer patients will exhibit the most favorable response to immunotherapy.

• MSI testing is conducted on tumor samples obtained from a patient. Typically, it relies on the analysis of five microsatellite markers. This testing can ascertain whether a tumor exhibits high microsatellite instability (MSI), low MSI, or is stable.

• Tumors are classified as high MSI (MSI-H) when there is evidence of instability in at least two of the five markers. High microsatellite instability (MSI) in patients with colorectal cancer indicates a high likelihood of having Lynch syndrome, which is the predominant cause of hereditary colon cancer.

• Low Microsatellite Instability: Tumors classified as low MSI (MSI-L) exhibit instability in only one of the five markers.

• Microsatellite Stable: Microsatellite stable (MSI-S) refers to the absence of instability in any of the markers.

• High Microsatellite Instability (MSI-H): Cancers exhibiting high microsatellite instability (MSI) are more prone to favorable responses to immunotherapy checkpoint inhibitor medications due to the presence of mutations that facilitate the treatment's identification of cancer cells.

1. Genetic counseling and testing can be employed to assess the risk of colorectal cancer in people who have not received a cancer diagnosis but have elevated or reduced MSI levels.
2. Individuals with consistently stable microsatellite instability (MSI) are typically not required to undergo genetic testing, as they are improbable to possess Lynch syndrome. Nevertheless, testing may still be employed if the patient has a familial predisposition to colorectal cancer.

• Patients must consult their doctors to understand how their MSI results may impact their available choices for cancer therapy.

What Are the Various Treatment Methods?

1. Surgical Procedure:

• Colorectal surgery can effectively excise many tumors.

• During a medical surgery known as segmental colectomy, a surgeon extracts a portion of the colon and subsequently reconnects the severed ends. During the initial phases of colon cancer, surgical intervention may suffice as the sole therapeutic approach.

• In certain cases, it is possible to surgically remove cancer that has metastasized to other organs or tissues.

2, Chemotherapy: Regional and systemic chemotherapy can potentially reduce the size of tumors and inhibit cancer metastasis. It can be utilized independently or in conjunction with other therapies. Chemotherapy medications utilized for the treatment of colon cancer encompass:

• Fluoropyrimidine- An anti-metabolite inhibits the synthesis of DNA components in the chemotherapy regimen.

• Irinotecan- They are anti-cancer drug it is used to control and treat a wide range of solid tumors.

• Oxaliplatin- They are chemotherapy drug, alkylating agents are substances that react with electron-rich atoms in biological molecules to produce covalent bonds, which is a type of chemotherapy.

3. Immunotherapy: Immunotherapy holds great potential as a treatment option for various forms of cancer. Immunotherapy is a method of enhancing one's own immune system to combat cancer.

• There are now three immune checkpoint inhibitors that have been authorized for the treatment of metastatic colon cancer with high levels of microsatellite instability (MSI-high). Intravenous infusions administer all of them.

• A therapeutic approach that specifically targets and acts on certain molecules or pathways involved in a disease.

• Colon cancer- Targeted therapies inhibit angiogenesis, generating new blood vessels and preventing tumor growth. The following items are included:

• These are the names of three drugs: Bevacizumab, Ramucirumab, and Ziv-aflibercept.

• They are often taken intravenously, frequently in conjunction with chemotherapy.

• Additional medications specifically target the epidermal growth factor receptor (EGFR), a pivotal protein that facilitates the proliferation of cancer cells. Two therapy options are Cetuximab and Panitumumab.

• In cases of cancer with BRAF gene mutations, physicians may employ targeted therapy medications such as Encorafenib and Regorafenib.

4. Radiation Therapy: Radiation therapy involves the focused delivery of high-energy radiation to a specific body region. This treatment can potentially reduce the size of tumors and eliminate cancer cells.

Conclusion

MSI colorectal cancer affects people of all ages and is typically seen in the right colon. It produces mucin and has a high lymphocyte infiltration. Immunohistochemistry, as the sole method for diagnosing microsatellite instability, may miss many MSI tumors due to its low sensitivity and high rate of false negative results compared to molecular studies using DNA sequencing. For instances with clinical suspicion of MSI and negative immunohistochemistry results, we recommend doing molecular tests and DNA sequencing.