Colon cancer is not a single entity but a diverse group of malignancies. Modern medical understanding recognizes that colon cancer is a heterogeneous collection of tumors that can be distinguished by where they originate, how their cells look, and the specific genetic changes they carry. Identifying these distinct subtypes is fundamental because these classifications directly influence a patient’s prognosis and the most effective course of treatment. The process of analyzing a tumor involves multiple layers of classification, moving from broad anatomical location to microscopic cellular features and finally to the molecular blueprint of the cancer cells.
Types Defined by Cell Structure
The most common way to initially classify colon cancer involves examining the tumor cells under a microscope, a process called histology. The vast majority of colon cancers, accounting for 90 to 95 percent of all cases, are categorized as adenocarcinomas. This means the cancer originated in the glandular cells that line the inner surface of the colon.
Even within adenocarcinomas, pathologists identify less common variants with distinct biological behaviors. Mucinous adenocarcinoma is one such variant, defined by the presence of at least 50 percent of the tumor volume being composed of extracellular mucus. These tumors can sometimes be more aggressive or respond differently to standard chemotherapy.
Another rare but highly aggressive subtype is signet ring cell carcinoma, which accounts for less than one percent of colon cancers. These cells are named for their distinctive microscopic appearance, where a large mucus vacuole pushes the cell’s nucleus to one side. Rarer still are types like squamous cell carcinoma, which arise from flat, skin-like cells and are typically treated differently than glandular adenocarcinomas.
Types Defined by Location in the Colon
Beyond cellular structure, the location of the tumor within the large intestine is a major defining characteristic that impacts the cancer’s biology and clinical presentation. The colon is divided into right-sided (proximal) and left-sided (distal) sections, which exhibit different behaviors.
Right-sided tumors occur in the cecum, ascending colon, and the first two-thirds of the transverse colon. They often grow as flatter lesions, making them harder to detect early during a standard colonoscopy, and commonly present with non-specific symptoms such as unexplained anemia. Right-sided tumors frequently display a distinct molecular profile, often being Microsatellite Instability-High (MSI-H) and sometimes associated with the BRAF mutation.
Conversely, left-sided tumors are found in the remainder of the transverse colon, descending colon, and sigmoid colon. These cancers more frequently grow as protruding masses, which can lead to earlier symptoms like changes in bowel habits or obstruction. Left-sided tumors are typically characterized by a high rate of mutations in the KRAS gene.
Rectal cancer, while anatomically part of the distal colon, is often discussed separately because its tight pelvic location necessitates a distinct treatment approach.
Types Defined by Molecular and Genetic Markers
The most precise and modern method of classification involves analyzing the tumor’s genetic and molecular markers, which are critical for predicting behavior and guiding therapy. One significant marker is Microsatellite Instability (MSI), which results from a defect in the cell’s DNA Mismatch Repair (MMR) system. Tumors that are Mismatch Repair-deficient (dMMR) or MSI-High (MSI-H) have a large number of mutations, indicating that the cell’s error-checking mechanism is faulty.
In contrast, most colon cancers are Microsatellite Stable (MSS) and Mismatch Repair-proficient (pMMR), meaning their DNA repair systems are intact. The MSI-H subtype is clinically distinct, often associated with right-sided cancers and highly responsive to immunotherapy. The presence of a germline MMR defect is the defining feature of Lynch Syndrome, a hereditary condition that predisposes individuals to this specific type of colon cancer.
Tumor classification also relies on identifying specific mutations in key genes that drive cancer growth. Mutations in the KRAS gene are the most frequent, found in roughly 50 percent of sporadic cases, and are often associated with MSS tumors. Mutations in the NRAS gene are less common.
Activating mutations in the BRAF gene, particularly V600E, are often found in MSI-H tumors and carry a worse prognosis. These genetic alterations are generally mutually exclusive, meaning a tumor typically has a mutation in one but not both of the KRAS or BRAF genes.
How Classification Determines Treatment Strategy
The comprehensive classification of a colon cancer tumor is fundamental to establishing an effective and individualized treatment plan. Knowing the tumor’s histology, location, and molecular profile allows oncologists to make informed decisions about surgery, chemotherapy, and targeted therapies.
For instance, the presence of MSI-H status is a strong indicator that the tumor will respond favorably to immune checkpoint blockade, a type of immunotherapy. The status of the RAS genes (KRAS and NRAS) is a critical determinant for using targeted drugs known as anti-Epidermal Growth Factor Receptor (EGFR) inhibitors.
If a tumor is found to have a KRAS or NRAS mutation, those targeted drugs will likely be ineffective, requiring the treatment plan to pivot to other options. Furthermore, the location of the tumor can influence the choice of chemotherapy, as left-sided cancers often show a more robust response to certain standard chemotherapies.
Treatment for rectal cancer, due to its confined location in the pelvis, often involves radiation therapy administered before surgery, a protocol distinct from most colon cancers.