Comparison of somatic mutations and clinicopathologic features of micropapillary and non-micropapillary colorectal carcinomas.

Abstract

Background: Micropapillary carcinoma (MPC) is a type of tumor that is histopathologically characterized by the presence of small papillary structures. Literature data on somatic mutations in MPCs are very limited.

Methods: One hundred fifty-nine colon resection cases diagnosed with adenocarcinoma whose DNA mutations were analyzed by next-generation sequencing (NGS) were retrospectively reviewed. In 10 cases, the MPC area exceeded 5%. Chi-square test was used to evaluate histopathologic characteristics and somatic mutations in MPCs and non-MPCs. The relationship between mutations and clinicopathological parameters in all cases was investigated.

Results: The presence of MPC areas in carcinomas was associated with higher histologic grades (MPC: n = 6; 60% vs. non-MPC: n = 22; 14.8%), more advanced pathologic T (pT4 MPC: n = 5; 50% vs. non-MPC: n = 46; 34.6%) and N stages (pN2b MPC: n = 5; 50% vs. non-MPC: n = 26; 19.5%) and more frequent tumor deposits (MPC: n = 7; 87.5% vs. non-MPC: n = 44; 46.8%), lymphovascular invasion (MPC: n = 8; 80% vs. non-MPC: n = 83; 55.7%), and perineural invasion (MPC: n = 7; 70% vs. non-MPC: n = 42; 28.2%). A significant difference was found between MPCs and non-MPCs in terms of histological grade (p = 0.002) and perineural invasion (p = 0.01). TP53, KRAS, and PIK3CA genes were the most frequently mutated genes in both MPCs and non-MPCs (TP53 MPC: n = 6; 100% vs. non-MPC: n = 72; 64.9% - KRAS MPC: n = 4; 40% vs. non-MPC: n = 66; 44.3% - PIK3CA MPC: n = 2; 20% vs. non-MPC: n = 32; 21.5%). There was no statistically significant difference in somatic mutations between the groups (TP53: p = 0.177, KRAS: p = 1.000, PIK3CA: p = 1.000, BRCA2: p = 0.181, ERBB2: p = 0.327, BRAF: p = 1.000, MAP2K1: p = 0.062). A significant difference was found between the TP53 mutant and TP53 wild-type groups in terms of tumor deposits (p = 0.033) and perineural invasion (p = 0.046). The male rate was significantly higher in KRAS wild-type cases (n = 69; 77.5%) compared to KRAS mutant cases (n = 38; 54.3%) (p = 0.002). The mean age, T and N staging were significantly different between PIK3CA mutant and PIK3CA wild-type cases (p = 0.01; p = 0.033; p = 0.019, respectively).

Conclusions: We found that MPCs had more advanced clinical stages and histological features associated with poor prognosis, such as advanced T and N stages, higher histological grade, presence of tumor deposits, lymphovascular and perineural invasion.