Microsatellite instability-high status enhances lymph node yield and reduces optimal dissection thresholds in...

Colorectal cancer is a leading cause of cancer-related mortality, and radical surgical resection remains the primary curative treatment. Adequate lymph node acquisition is critical for accurate staging and treatment planning. It is well established that the microsatellite instability status, particularly the high microsatellite instability phenotype, influences tumor biology and immune responses. However, the impact of high microsatellite instability on lymph node retrieval in Chinese patients with colorectal cancer remains unclear. This study investigates the correlation between the microsatellite instability status and lymph node acquisition after colorectal cancer resection and evaluates the adequacy of lymph node counts using a statistical model.

A retrospective analysis was conducted with 4,205 patients with colorectal cancer who underwent surgical resection at the First Medical Center of the Chinese People's Liberation Army General Hospital from January 2018 to June 2023. Patients with primary colorectal cancer who underwent R0 resection were included, whereas those receiving neoadjuvant therapy or with distant metastasis were excluded. The microsatellite instability status was determined by immunohistochemical analysis of mismatch repair proteins and polymerase chain reaction-based microsatellite marker testing. Lymph node retrieval and adequacy were assessed, and the β-binomial distribution model was used to estimate the probability of occult lymph node disease.

Among the 4,205 patients, 309 cases (7.3%) were diagnosed as high microsatellite instability-type colorectal cancer. Patients with high microsatellite instability exhibited distinct clinicopathologic features, including larger tumor size, higher prevalence of mucinous adenocarcinoma, and poorer differentiation. Compared with patients with microsatellite stability, the high microsatellite instability status was significantly associated with a higher median lymph node count (18 vs 15, P < .001) and an adequate lymph node acquisition rate (96.1% vs 88.1%, P = .037). This association was more pronounced in colon cancer, where the high microsatellite instability status was an independent predictor of increased lymph node yield (β = 1.619, P < .001). In rectal cancer, no significant association was observed between the high microsatellite instability status and lymph node yield. The β-binomial distribution model indicated that compared with patients with microsatellite stability, patients with high microsatellite instability required fewer lymph nodes to achieve the same false-negative rate, suggesting that the microsatellite instability status should be considered in lymph node dissection strategies.

The high microsatellite instability phenotype is significantly associated with a higher lymph node count and adequate lymph node acquisition in patients with colorectal cancer, particularly in those with colon cancer. This may be attributed to the enhanced immune response and lymph node microenvironment remodeling characteristic of high microsatellite instability tumors. These findings underscore the importance of integrating the microsatellite instability status into surgical planning and lymph node dissection strategies for patients with colorectal cancer. Future multicenter prospective studies are warranted to validate these results and further explore the underlying mechanisms.