Colorectal cancer with microsatellite instability: Right-sided location and signet ring cell histology are associated with nodal metastases, and extranodal extension influences disease-free survival

Colorectal cancer (CRC) with microsatellite instability (MSI) accounts for 15-18 % of all CRCs and represents the category with the best prognosis. This study aimed at determining any possible clinical/pathological features associated with a higher risk of nodal metastasization in MSI-CRC, and at defining any possible prognostic moderators in this setting. All surgically resected CRCs of the last 20 years (mono-institutional series) with a PCRbased diagnosis of MSI, with and without nodal metastasis, have been retrieved for histological review, which was performed following WHO guidelines. Furthermore, the most important prognostic moderators have been investigated with a survival analysis. The study of 33 cases of MSI-CRCs with nodal metastasis highlighted a high fidelity of histology maintenance between primary tumors and matched nodal metastases. At survival analysis, the strongest prognostic variable in MSI-CRCs with nodal metastasis was the extranodal extension (multivariate analysis, HR: 14.4, 95 %CI: 1.46-140.9, p = 0.022). Furthermore, through a comparison between nodal positive (33 cases) and nodal negative (71 cases) MSI-CRCs, right-sided location (p < 0.0001), pT4 stage (p = 0.0004) and signet-ring histology (p = 0.0089) emerged as parameters more commonly associated with nodal metastasization. These findings shed new light on the biology of MSI-CRC and can be of help for the prognostic stratification of MSI-CRC patients.