Loss of HES-1 Expression Predicts a Poor Prognosis for Small Intestinal Adenocarcinoma Patients.

Hairy and enhancer of split-1 (HES-1), which is a downstream target of the Notch signaling pathway, has been linked to mutations. HES-1 has been proposed as harboring oncogenic activity in colorectal cancer but has not been investigated in adenocarcinoma of the small intestine, where the drivers of oncogenesis are not as well-understood. To investigate the clinicopathologic and prognostic implications of HES-1, HES-1 immunohistochemical expression was analyzed in digital images along with clinicopathological variables, including survival and genotype, in 185 small intestinal adenocarcinomas. The loss of HES-1 expression (HES-1) was observed in 38.4% (71/185) of the patients, and was associated with higher pT category ( = 0.018), pancreatic invasion ( = 0.005), high grade ( = 0.043), and non-tubular histology ( = 0.004). Specifically, in tumors with mutant ( ), HES-1 was related to proximal location ( = 0.024), high T and N categories ( = 0.005 and 0.047, respectively), and pancreatic invasion ( = 0.004). Patients with HES-1 showed worse overall survival compared to those with intact HES-1 (HES-1) ( = 0.013). Patients with HES-1/ (median, 17.3 months) had significantly worse outcomes than those with HES-1/ (39.9 months), HES-1/ (47.6 month), and HES-1/ (36.2 months; = 0.010). By multivariate analysis, HES-1 (hazard ratio = 1.55, 95% confidence interval (CI), 1.07-2.26; = 0.022) remained an independent prognostic factor. HES-1expression can be used as a potential prognostic marker and may aid in the management of patients with small intestinal adenocarcinomas.