Understanding a colon cancer’s specific subtype is a significant part of forming an effective treatment plan. The most common subtype is Microsatellite Stable (MSS) colon cancer, which accounts for the vast majority of diagnoses. This classification refers to the genetic characteristics of the tumor cells and helps guide medical professionals in selecting the most appropriate therapies.
Understanding Microsatellite Stability
Our DNA contains short, repeating sequences known as microsatellites. A system called mismatch repair (MMR) functions like a spell-checker, correcting errors that occur when DNA is copied. Microsatellite Stable (MSS) means this MMR system is proficient, or working correctly, within the cancer cells. Consequently, the number of mutations in these repetitive DNA segments remains low.
This stability is a feature of about 85% of all colorectal cancers and stands in contrast to Microsatellite Instability (MSI), where the MMR system is faulty. In MSI tumors, errors in the DNA code are not fixed, leading to a high number of mutations. The proper functioning of the MMR system involves several genes, including MLH1, MSH2, MSH6, and PMS2, which produce the proteins that carry out DNA repair.
Diagnosis and Staging of MSS Colon Cancer
The diagnosis of MSS colon cancer begins with a colonoscopy, where a physician removes a suspicious polyp or tissue sample for a biopsy. Once cancer is confirmed, the tumor tissue undergoes molecular testing to determine its microsatellite status. This step is a routine part of the analysis for all colorectal cancers to guide treatment decisions.
Two primary methods determine this status. Immunohistochemistry (IHC) tests the tumor for the presence of mismatch repair proteins; if all expected proteins are present, the tumor is classified as MSS. Another method is Polymerase Chain Reaction (PCR), a DNA-based test that analyzes the length of specific microsatellite sequences in the tumor’s DNA.
This molecular diagnosis is combined with the cancer’s physical stage. Staging is determined using the TNM system, which assesses the primary tumor’s size (T), spread to nearby lymph nodes (N), and metastasis (M) to distant parts of the body. The stage is a primary factor in determining a patient’s overall prognosis.
Treatment Approaches for MSS Colon Cancer
Treatment for MSS colon cancer primarily depends on the cancer’s stage at diagnosis. For localized tumors, surgery to remove the cancerous portion of the colon is the main intervention. Following surgery, adjuvant chemotherapy may be recommended for Stage III and some high-risk Stage II cancers to eliminate remaining cancer cells and reduce the risk of recurrence.
Standard chemotherapy regimens are the foundation of treatment. A common combination is FOLFOX, which includes fluorouracil (5-FU), leucovorin, and oxaliplatin. For rectal cancers, radiation therapy is often used with chemotherapy to shrink the tumor and destroy local cancer cells.
The MSS classification has implications for immunotherapy. Immune checkpoint inhibitors, a type of immunotherapy that helps the body’s immune system attack cancer, are highly effective against MSI-H tumors. These treatments are generally not effective for MSS tumors because the low number of mutations makes them less “visible” to the immune system.
Prognosis and Emerging Therapies
The prognosis for MSS colon cancer is most strongly influenced by the cancer’s stage when it is found. Early-stage cancers that have not spread beyond the colon wall have a much better outcome than those that have metastasized. The cancer’s stage at diagnosis remains the most significant prognostic factor.
Patients with MSS tumors may have a slightly higher risk of the cancer returning compared to those with MSI-H tumors, especially in earlier stages. Established treatment protocols involving surgery and chemotherapy have been refined over many years and offer a clear path for managing the disease. The predictability of MSS cancer’s response to these treatments provides a solid foundation for care.
Research is actively exploring ways to improve outcomes for MSS colon cancer, particularly for advanced disease. Clinical trials are investigating new strategies, such as combining immunotherapy with other drugs to make “cold” MSS tumors more recognizable to the immune system. Other studies are focused on targeted therapies that block specific proteins involved in cancer cell growth.