Kim Jeong Won, Jun Sun-Young, Ylaya Kris, Chang Hee-Kyung, Oh Young-Ha, Hong Seung-Mo, Chung Joon-Yong, Hewitt Stephen M
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea.
Front Oncol. 2020 Aug 19;10:1427. doi: 10.3389/fonc.2020.01427. eCollection 2020.
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.
毛状分裂增强子1（HES-1）是Notch信号通路的下游靶点，与突变有关。HES-1被认为在结直肠癌中具有致癌活性，但尚未在小肠腺癌中进行研究，因为小肠腺癌的致癌驱动因素尚未完全明确。为了研究HES-1的临床病理和预后意义，对185例小肠腺癌的数字图像进行了HES-1免疫组化表达分析，并结合包括生存和基因型在内的临床病理变量进行分析。38.4%（71/185）的患者出现HES-1表达缺失（HES-1），且与更高的pT分期（P = 0.018）、胰腺侵犯（P = 0.005）、高级别（P = 0.043）和非管状组织学（P = 0.004）相关。具体而言，在具有KRAS突变（KRAS）的肿瘤中，HES-1与近端位置（P = 0.024）、高T和N分期（分别为P = 0.005和0.047）以及胰腺侵犯（P = 0.004）有关。与HES-1完整（HES-1）的患者相比，HES-1缺失的患者总生存期更差（P = 0.013）。HES-1/KRAS（中位生存期，17.3个月）的患者预后明显比HES-1/KRAS（39.9个月）、HES-1/BRAF（47.6个月）和HES-1/野生型（36.2个月；P = 0.010）的患者更差。通过多变量分析，HES-1（风险比 = 1.55，95%置信区间（CI），1.07 - 2.26；P = 0.022）仍然是一个独立的预后因素。HES-1表达可作为一种潜在的预后标志物，可能有助于小肠腺癌患者的管理。
