Tissue Biomarker in Colorectal Carcinoma

Globally, colorectal cancer represents one of the most frequently diagnosed malignancies, accounting for approximately 1.9 million new cases in 2022, making it the third most common cancer worldwide. Heterogeneous pathogenetic mechanisms in colorectal cancer give rise to distinct tumor phenotypes, which manifest as specific clinical characteristics, treatment response, and prognostic outcome. Tissue biomarkers provide diagnostic and prognostic information, enabling accurate identification of tumor origin and subtypes as well as guiding personalized treatment strategies. However, despite their clinical importance, tissue biomarkers are not yet optimally implemented in routine practice, potentially limiting the treatment effectiveness. Immunohistochemical patterns of CK7/CK20 are useful for identifying the primary origin of colorectal tumors. The use of CK7/CK20 combined with CDX2 and SATB2 yields a powerful diagnostic panel for colorectal cancer. A profile of CK7-negative, CK20-positive, CDX2-positive, SATB2-positive represents a reliable immunohistochemical signature. Analysis of DNA mismatch repair (MMR) proteins such as MLH1, MSH2, MSH6, and PMS2 serves as an initial screening tool to differentiate hereditary colorectal cancer (Lynch syndrome) from sporadic colorectal cancer. Furthermore, KRAS mutations predict resistance to anti-EGFR agents, including cetuximab and panitumumab, and are associated with worse progression-free survival, whereas tumors harboring the BRAF V600E mutation tend to exhibit aggressive biological features and suboptimal response to standard chemotherapy. Comprehensive evaluation of tissue biomarkers prior to treatment initiation enables molecularly tailored therapeutic approaches, ultimately improving treatment efficacy and overall clinical outcomes.