Expression of the Serrated Markers Annexin A10 or Gremlin1 in Colonic Adenocarcinomas: Morphology and Prognostic Values

Abstract

Describe clinical, histological and molecular charatcteristics and prognosis values of the serrated candidate markers AnnexinA10 and Gremlin1 in colon adenocarcinomas. Immunohistochemical expression of AnnexinA10 and Gremlin1 was evaluated on 346 colonic adenocarcinomas. Clinicopathological, molecular features and prognostic characteristics were then evaluated. A total of 40 colonic adenocarcinomas expressed AnnexinA10 (11.6%) and, 115 expressed Gremlin1 (40.4%). AnnexinA10 expression was significantly associated, on univariate analyses, with female gender (p = 0.03), right tumor location (p < 0.001), differentiation grade 3 (p < 0.001), serrated adenocarcinoma subtype (p < 0.001), serrated (p < 0.001), medullary (p = 0.005), and mucinous component (p = 0.004), cytoplasmic eosinophilia (p < 0.001), discernible nuclei (p = 0.001), preserved polarity (p < 0.001), lymphatic invasion (p = 0.01), BRAFV600E mutation (p < 0.001), MSI-H status (p < 0.001) and CIMP-H status (p = 0.019). Multivariate analyses revealed that mucinous component (p = 0.002), lymphatic invasion (p = 0.02) and BRAFV600E mutation (p < 0.001) were independently associated with AnnexinA10 expression. In addition, AnnexinA10 was an indicator of poorer overall survival (OS) in UICC stage IV adenocarcinomas (p = 0.01) only. Gremlin1 expression was neither associated with serrated adenocarcinoma subtype (p = 0.51) nor with AnnexinA10 expression (p = 0,31), but was significantly associated, in univariate analysis with male gender (p = 0.002), younger age (p = 0.002), left tumor location (p = 0.04), and MSS status (p = 0.03). Gremlin1 expression was associated with better OS only in UICC stage III colon adenocarcinomas (p = 0.006). Colon adenocarcinomas expressing AnnexinA10 have distinct clinico-pathological and molecular features. AnnexinA10 expression is an indicator of poorer OS in UICC stage IV patients. Gremlin1 expression is not associated with serrated adenocarcinomas subtype. Its expression was associated with better OS in UICC Stage III patients.