scholarly journals Sexual dimorphism in small-intestinal neuroendocrine tumors: lower prevalence of mesenteric disease in premenopausal women

2022 ◽  
Author(s):  
Anela Blažević ◽  
Anand M Iyer ◽  
Marie-Louise F van Velthuysen ◽  
Johannes Hofland ◽  
Lindsey Oudijk ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Sexual Dimorphism ◽  
Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Estrogen Receptor Alpha ◽  
Premenopausal Women ◽  
Primary Tumors ◽  
Tertiary Center ◽  
Male Patients ◽  
Small Intestinal

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 Retrospectively, SI-NET patients treated in a single tertiary center were included and analyzed for disease characteristics. Estrogen receptor 1 (ESR1) and 2 (ESR2), progesterone receptor (PGR) and androgen receptor (AR) mRNA expression was assessed in primary tumors and healthy intestine. Estrogen receptor alpha (ERα) and AR protein expression was analyzed by immunohistochemistry in primary tumors and mesenteric metastases. 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). 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.

Immunohistochemical biomarker expression in gastro-entero-pancreatic neuroendocrine tumors at ENETS Centre of Excellence, University Hospital Zurich, Switzerland.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15673-e15673
Author(s):  
Silvia Duschek ◽  
Juliane Friemel ◽  
Alessandra Curioni Fontecedro ◽  
Alexander Rheinhard Siebenhuener
Keyword(s):  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Tissue Microarray ◽  
Neuroendocrine Tumors ◽  
Estrogen Receptor Α ◽  
University Hospital ◽  
Pancreatic Neuroendocrine Tumors ◽  
Biological Behaviour ◽  
Primary Tumors ◽  
Therapy Targets

e15673 Background: Gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) are a heterogeneous tumor entity with respect to biological behaviour and prognosis. Definition of new predictive and prognostic biomarkers as well as new therapy targets are of upmost clinical interest. Methods: At the ENETS CoE Zurich tissue microarray (TMA) blocks were constructed with 147 tissue samples of tumors diagnosed from 2000 to 2017, including primary tumors and metastasis. Tissue microarray sections were immunostained for SOX-9, SOX-10, SSTR-2 +, PDL-1, thyroid transcription factor 1 (TTF1), estrogen receptor-α (ER-α) and -β (ER-β), progesterone receptor (PR), androgen receptor (AR), BRAF and HER2. Results: In total 270 patients were screened between 2000 - 2017 and 92 patient’s material were sufficient for TMA analysis. Subgroup analysis showed 32 pancreatic, 37 ileum, 10 duodenum, 7 appendix, 3 colorectal, 3 gastric and 1 NET of gallbladder. 50% were male, the median age 63.5 years (range 19-88y). AR, ER-β, TTF1, PDL-1 and SOX10 was only present in a small number of NETs. HER2 and BRAF were negative in all samples. We found ER-α expression in 27.2%, 30% were PR positive and 67.4% showed SOX9 expression. Conclusions: We identified a frequent expression of new markers as SOX9, progesterone receptor and estrogen receptor-α in a broad amount of samples and a potential correlation with tumor grade. This finding might implicate a prognostic or predictive value of these markers, as well as it reveals new potential therapy targets for GEP-NETs. Therefore, further analyses are planned.

scholarly journals The association of the angiopoietin/Tie-2 system with the development of metastasis and leukocyte migration in neuroendocrine tumors

2010 ◽  
Vol 17 (4) ◽  
pp. 897-908 ◽  
Author(s):  
Nicté Figueroa-Vega ◽  
Ángel Díaz ◽  
Magdalena Adrados ◽  
Cristina Álvarez-Escolá ◽  
Amalia Paniagua ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Serum Levels ◽  
Soluble Form ◽  
Blood Monocytes ◽  
Rt Pcr ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Primary Tumors ◽  
Enhanced Expression ◽  
And Function

The aim of this study was to explore the possible involvement of the angiopoietin (Ang)-1, -2/Tie-2 system in the development, growth, and metastases evolution of gastroenteropancreatic-neuroendocrine tumors (GEP-NETs). We prospectively examined the serum levels of Tie-2, Ang-1, and Ang-2 by ELISA in 42 patients with proven GEP-NETs and 27 controls. We also determined the expression of the Ang/Tie-2 system in freshly isolated peripheral blood monocytes and in tumor cells from malignant primary tumors and/or liver metastases samples from GEP-NET patients by flow cytometry and/or RT-PCR. Furthermore, the function of the Ang/Tie-2 system in monocytes from controls and patients was assessed by a chemotaxis assay. GEP-NET patients showed enhanced serum levels of soluble form of Tie-2 (sTie-2), Ang-1, and Ang-2 (P<0.05 in all cases), compared to controls. sTie-2 and Ang-2 levels were significantly higher in GEP-NETs with metastases compared to those with no metastases. In addition, a significant correlation was detected between Ang-2 levels and chromogranin A or sTie-2 concentrations or 5-hydroxy-indole acetic acid excretion (r=0.71, r=0.60, and r=0.81 respectively, P<0.01 in all cases). Furthermore, we observed an enhanced expression of Ang-1, Ang-2, and Tie-2 in freshly isolated tumor cells from GEP-NET both by immunohistochemistry and by RT-PCR. Interestingly, an enhanced expression and function of Tie-2 was detected in monocytes from GEP-NET patients. Our data suggest that the Ang/Tie-2 system is involved in the growth and development of metastases of GEP-NETs, and that favors the recruitment of Tie-2+ monocytes to the tumor site, where they can promote inflammation and angiogenesis.

scholarly journals Increased expression of the estrogen receptor alpha, ESR1, in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Estrogen Receptor Α ◽  
Needle Aspiration ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Transcriptional Induction ◽  
Selection Of

Hormones function as growth factors, and estrogen provides growth signals to support and induce the proliferation of breast cancers (1-3). This is the basis of the use of endocrine therapies (4, 5) including tamoxifen and letrozole as first-line treatment for patients with breast cancer. We found through mining published microarray and multiplexed gene expression profiling datasets that the estrogen receptor α (ESR1) was among the genes most differentially expressed in the primary tumors and fine needle aspiration-isolated tumor cells of patients with breast cancer treated with trastuzumab. However, estrogen receptor α was expressed at higher rather than lower levels in the tumors of trastuzumab-treated patients. These data, obtained through blind, systems-level analysis of published microarray data (6-8), suggest that trastuzumab administration in patients with breast cancer is associated with transcriptional induction of the estrogen receptor or selection of tumor clones with high expression of ESR1.

scholarly journals Primary small intestinal neuroendocrine tumors are highly prevalent and often multiple before metastatic disease develops

2019 ◽  
pp. 145749691987448 ◽  
Author(s):  
J. Eriksson ◽  
O. Norlén ◽  
M. Ögren ◽  
H. Garmo ◽  
C. Ihre-Lundgren ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Metastatic Disease ◽  
High Rate ◽  
Primary Tumors ◽  
The People ◽  
Swedish Cancer Registry ◽  
The Mean ◽  
Small Intestinal ◽  
Diagnostic Modalities

Background: Small intestinal neuroendocrine tumors are the most common of small bowel malignancies with a clinical incidence of about 1 per 100,000 persons per year. There has been a threefold increase in the incidence of small intestinal neuroendocrine tumor during later decades, but there are no studies that clarify whether this is due to a true higher incidence or if the rise is a mere product of, for instance, improved diagnostic modalities. The aim of this study was to investigate the incidence of clinical as well as subclinical small intestinal neuroendocrine tumors found at autopsy as well as describing the frequency of concomitant malignancies in patients with small intestinal neuroendocrine tumor. Materials and methods: An autopsy registry from the Malmö county population from 1970 to 1982 with an 87% autopsy rate was used. The clinical autopsy reports for patients coded for the existence of “carcinoid tumor” were scrutinized for the presence of small intestinal neuroendocrine tumor, metastatic disease, and concomitant malignancies. Details of patients with clinically diagnosed small intestinal neuroendocrine tumor during this time period were gathered from the Swedish Cancer Registry. Results: The mean annual incidence of small intestinal neuroendocrine tumor during this period was 5.33 per 100,000 individuals, and the mean annual prevalence was 581 per 100,000. The cause of death in the majority of cases was not due to small intestinal neuroendocrine tumor. In total, 48% of the people with small intestinal neuroendocrine tumor had at least one other malignancy, most commonly colorectal cancer. Conclusion: Most small intestinal neuroendocrine tumors are subclinical, and persons living with them will often die due to other causes. There was a high rate of multiple primary tumors (40%), suggesting that multiple tumors seem to arise before the advent of metastatic disease. Moreover, a comparably high rate of associated colorectal carcinoma was found.

scholarly journals High expression of estrogen receptor alpha and aromatase in glial tumor cells is associated with gender-independent survival benefits in glioblastoma patients

2020 ◽  
Vol 147 (3) ◽  
pp. 567-575
Author(s):  
Lisa Stefanie Hönikl ◽  
Friederike Lämmer ◽  
Jens Gempt ◽  
Bernhard Meyer ◽  
Jürgen Schlegel ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Tumor Cells ◽  
Estrogen Receptor Alpha ◽  
High Expression ◽  
Glial Tumor ◽  
Receptor Alpha

scholarly journals Spontaneous Basaloid Adenomas of the Mammary Gland in Four Dogs: Clinicopathologic and Immunohistochemical Features

2002 ◽  
Vol 39 (6) ◽  
pp. 739-743 ◽  
Author(s):  
J. Martín de las Mulas ◽  
J. Ordás ◽  
M. Y. Millán ◽  
A. Espinosa de los Monteros ◽  
C. Reymundo
Keyword(s):  
Estrogen Receptor ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Tumor Cells ◽  
Basal Cell ◽  
Estrogen Receptor Alpha ◽  
Progesterone Receptors ◽  
Receptor Alpha ◽  
Contraceptive Steroids

Spontaneous basaloid adenomas occurred in four out of 354 dogs with mammary tumors. Affected dogs were pure-bred, intact females between 6 and 8 years of age. Three dogs were nuliparous, two had pseudopregnancies, and none had received contraceptive steroids. The tumors were multiple (three cases) or unique, less than 1 cm in diameter, well delineated, and composed of uniform cords and clusters of monomorphic epithelial cells with focal signs of squamous or glandular differentiation. A basal cell immunophenotype (cytokeratins 5 and 14 positive) without either glandular epithelial (cytokeratins 8, 18, and 19 negative) or myoepithelial (calponin negative) differentiation was observed in the majority of tumor cells. No recurrence or metastasis was recorded after follow-up periods between 3 and 24 months. In spite of the hormone-dependent nature of this tumor in female Beagles given experimental contraceptive steroids, spontaneous basaloid adenomas lacked estrogen receptor alpha and progesterone receptors.

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