The association between microsatellite instability and lymph node count in colorectal cancer

The number of lymph nodes retrieved from colorectal cancer (CRC) resection specimens is crucial for adequate diagnosis and therapy. Previous studies indicate that in addition to the extent of surgical resection and the quality of pathological lymph node examination, non-modifiable tumour parameters like microsatellite instability (MSI) are associated with higher lymph node count. In order to study the potential influence of MSI on lymph node count, we analysed a previously MSI-typed population of CRC patients (n = 1196) to determine the relationship between MSI and the frequency with which at least 12 lymph nodes were retrieved, as well as the mean and median number of retrieved lymph nodes. MSI was associated with an increased frequency of 12-node retrieval, as well as a higher mean and median lymph node count in the overall analysis (p 0.004 and 0.001 for 12-node retrieval and lymph node count, respectively). However, when the analysis was restricted to cancers of the proximal colon, the main location of microsatellite unstable tumours (84% in our study), no association between MSI and 12-node retrieval was found. Subcategorisation by UICC stage of proximally located cancers showed a statistically significant increase in the lymph node count only in microsatellite unstable stage I tumours (p 0.010). In conclusion, our data shows that previously reported associations between MSI and higher lymph node count are mainly a consequence of the increased incidence of microsatellite unstable cancer in the proximal colon. Our finding that MSI is related to a significantly higher mean lymph node count in proximal stage I cancers may indicate that the immunogenicity of this molecular tumour type induces earlier lymph node activation.