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Loss of HES-1 Expression Predicts a Poor Prognosis for Small Intestinal Adenocarcinoma Patients
- Source :
- Frontiers in Oncology, Vol 10 (2020), Frontiers in Oncology
- Publication Year :
- 2020
- Publisher :
- Frontiers Media SA, 2020.
-
Abstract
- Objective: Hairy and enhancer of split-1 (HES-1), which is a downstream target of the Notch signaling pathway, has been linked to KRAS 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. Materials and Methods: 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 KRAS genotype, in 185 small intestinal adenocarcinomas. Results: The loss of HES-1 expression (HES-1Loss) was observed in 38.4% (71/185) of the patients, and was associated with higher pT category (P = 0.018), pancreatic invasion (P = 0.005), high grade (P =0.043), and non-tubular histology (P = 0.004). Specifically, in tumors with mutant KRAS (KRASMT), HES-1Loss was related to proximal location (P = 0.024), high T and N categories (P = 0.005 and P = 0.047, respectively), and pancreatic invasion (P = 0.004). Patients with HES-1Loss showed worse overall survival compared to those with intact HES-1 (HES-1Intact) (P = 0.013). Patients with HES-1Loss/KRASMT (median, 17.3 months) had significantly worse outcomes than those with HES-1Intact/KRASWT (39.9 months), HES-1Intact/KRASMT (47.6 month), and HES-1Loss/KRASWT (36.2 months) (P = 0.010). By multivariate analysis, HES-1Loss (hazard ratio = 1.55, 95% confidence interval (CI), 1.07 – 2.26; P = 0.022) remained an independent prognostic factor. Conclusion: HES-1 expression can be used as a potential prognostic marker and may aid in the management of patients with small intestinal adenocarcinomas.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_specialty
Colorectal cancer
medicine.disease_cause
lcsh:RC254-282
Gastroenterology
03 medical and health sciences
0302 clinical medicine
Internal medicine
KRAS
medicine
reproductive and urinary physiology
Original Research
adenocarcinoma
business.industry
Hazard ratio
Small Intestinal Adenocarcinoma
Histology
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Small intestine
030104 developmental biology
medicine.anatomical_structure
Oncology
HES-1
030220 oncology & carcinogenesis
Immunohistochemistry
Adenocarcinoma
prognosis
biological phenomena, cell phenomena, and immunity
business
small intestine
Subjects
Details
- ISSN :
- 2234943X
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Frontiers in Oncology
- Accession number :
- edsair.doi.dedup.....3d59e91c0933a5fde892774ee0c136ca