Abstract | CONTEXT: Small-intestinal neuroendocrine tumors (SI-NETs) have a modest but significantly higher prevalence and worse prognosis in male patients. OBJECTIVE: This work aims to increase understanding of this sexual dimorphism in SI-NETs. PATIENTS AND METHODS: RESULTS: Of the 559 patients, 47% were female. Mesenteric metastasis/ fibrosis was more prevalent in men (71% / 46%) than women (58% / 37%; P = 0.001 and P = 0.027, respectively). In women, prevalence of mesenteric metastases increased gradually with age from 41.1% in women <50 years to 71.7% in women >70 years. Increased expression of ESR1 and AR mRNA was observed in primary tumors compared to healthy intestine (both P < 0.001). ERα staining was observed in tumor cells and stroma with a strong correlation between tumor cells of primary tumors and mesenteric metastases (rho = 0.831, P = 0.02), but not in stroma (rho = -0.037, P = 0.91). AR expression was only found in stroma. CONCLUSION: Sexual dimorphism in SI-NETs was most pronounced in mesenteric disease, and the risk of mesenteric metastasis in women increased around menopause. The combination of increased ERα and AR expression in the SI-NET microenvironment suggests a modulating role of sex steroids in the development of the characteristic SI-NET mesenteric metastasis and associated fibrosis.
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Authors | Anela Blažević, Anand M Iyer, Marie-Louise F van Velthuysen, Johannes Hofland, Lindsey Oudijk, Wouter W de Herder, Leo J Hofland, Richard A Feelders |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 107
Issue 5
Pg. e1969-e1975
(04 19 2022)
ISSN: 1945-7197 [Electronic] United States |
PMID | 34999838
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. |
Chemical References |
- Estrogen Receptor alpha
- RNA, Messenger
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Topics |
- Estrogen Receptor alpha
(genetics, metabolism)
- Female
- Fibrosis
- Humans
- Intestinal Neoplasms
(epidemiology, genetics, metabolism)
- Intestine, Small
(metabolism)
- Male
- Middle Aged
- Neuroendocrine Tumors
(epidemiology, genetics, metabolism)
- Prevalence
- RNA, Messenger
(genetics, metabolism)
- Retrospective Studies
- Sex Characteristics
- Tumor Microenvironment
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