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

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.

2008 ◽  
Vol 28 (24) ◽  
pp. 7487-7503 ◽  
Author(s):  
Poornima Bhat-Nakshatri ◽  
Guohua Wang ◽  
Hitesh Appaiah ◽  
Nikhil Luktuke ◽  
Jason S. Carroll ◽  
...  

ABSTRACT Estrogen regulates several biological processes through estrogen receptor α (ERα) and ERβ. ERα-estrogen signaling is additionally controlled by extracellular signal activated kinases such as AKT. In this study, we analyzed the effect of AKT on genome-wide ERα binding in MCF-7 breast cancer cells. Parental and AKT-overexpressing cells displayed 4,349 and 4,359 ERα binding sites, respectively, with ∼60% overlap. In both cell types, ∼40% of estrogen-regulated genes associate with ERα binding sites; a similar percentage of estrogen-regulated genes are differentially expressed in two cell types. Based on pathway analysis, these differentially estrogen-regulated genes are linked to transforming growth factor β (TGF-β), NF-κB, and E2F pathways. Consistent with this, the two cell types responded differently to TGF-β treatment: parental cells, but not AKT-overexpressing cells, required estrogen to overcome growth inhibition. Combining the ERα DNA-binding pattern with gene expression data from primary tumors revealed specific effects of AKT on ERα binding and estrogen-regulated expression of genes that define prognostic subgroups and tamoxifen sensitivity of ERα-positive breast cancer. These results suggest a unique role of AKT in modulating estrogen signaling in ERα-positive breast cancers and highlights how extracellular signal activated kinases can change the landscape of transcription factor binding to the genome.


HPB ◽  
2020 ◽  
Vol 22 ◽  
pp. S299-S300
Author(s):  
M Montes Manrique ◽  
J Ortiz de Solórzano ◽  
JC Trujillo Diaz ◽  
M Rodríguez López ◽  
M Juarez Martin ◽  
...  

2006 ◽  
Vol 15 (3) ◽  
pp. 462-467 ◽  
Author(s):  
Fränzel J.B. van Duijnhoven ◽  
Petra H.M. Peeters ◽  
Ruth M.L. Warren ◽  
Sheila A. Bingham ◽  
André G. Uitterlinden ◽  
...  

Zygote ◽  
2014 ◽  
Vol 23 (5) ◽  
pp. 695-703 ◽  
Author(s):  
Zi Li Lin ◽  
He Min Ni ◽  
Yun Hai Liu ◽  
Xi Hui Sheng ◽  
Xiang Shun Cui ◽  
...  

SummaryIt is well established that estrogen and progesterone are critical endogenous hormones that are essential for implantation and pregnancy in females. However, the distribution of estrogen receptor α (ERα) and progesterone receptor (PR) in female reproductive tracts is elusive. Herein, we report that after serial treatments with pregnant mare's serum gonadotrophin (PMSG) with or without anti-PMSG (AP), mice could regulate the distribution of ERα and PR in the murine ovary, oviduct and uterus and the level of estradiol in serum. ERα and PR regulation by PMSG and anti-PMSG was estrous cycle-dependent and critical for promoting the embryo-implantation period. Furthermore, our results suggested that AP-42 h treatment is more effective than the other treatments. In contrast, other treatment groups also affected the distribution of ERα and PR in mouse reproductive tracts. Thus, we found that anti-PMSG has the potential to restore the distribution of ERα and PR, which could effectively reduce the negative impact of residual estrogen caused by the normal superovulation effect of PMSG in mice.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15183-e15183
Author(s):  
Aakanksha Asija ◽  
Stacey Milan ◽  
Anthony Prestipino ◽  
Charles Yeo ◽  
Madhavan V. Pillai

e15183 Background: Pancreatic neuroendocrine tumors(pNET) are rare tumors accounting for less than 5% of pancreatic cancer. They are functionally and biologically heterogeneous and have not been studied in great detail until recently. Methods: We conducted a retrospective review of 79 consecutive patients with pNET diagnosed and treated at Thomas Jefferson University Hospital between the years of 2000 and 2010. Results: Of the 79 patients whose records were reviewed, 32 were male and 47 were female. Median age at diagnosis was 61 years. Two cases were associated with MEN1 syndrome. Primary tumor arose in the head, body and tail of the pancreas in 15, 10 and 26 patients, resp. In 6 patients, the tumor was multifocal. The neuroendocrine tumor was accompanied by pancreatic adenocarcinoma in 1 patient and intraductal papillary mucinous neoplasm in 3. In 10 patients, distant metastasis was detected, involving liver only. Tumor was functional in 9 patients: 5 insulinoma, 2 gastrinoma,1 glucagonoma and 1 VIPoma. As per TNM staging, 28, 22 and 10 patients were Stage I, II and III, and IV at diagnosis. Treatment by surgical resection was undertaken in 54 patients. In 21 patients, the tumor was discovered incidentally; 21 patients presented with abdominal pain. Other symptoms were irregular bowel movements, weight loss and jaundice. 51 of the 79 (64.5%) patients were alive at last follow up. On univariate analysis, median survival for females was 137 months vs 114 months for male. Median survival for patients with functional tumors was similar to those with nonfunctioning tumors (118 and 115 months, resp). Median survival for patients with Stage I, II, and III and Stage IV patients were 234,112 and 40 months resp. Median survival for patients who underwent surgical resection was 130 months vs those who did not (30 months). Conclusions: Majority of pNET were located in the body and tail of pancreas; an area requiring thorough scrutiny with special imaging studies for diagnosis. Only a minority of patients presented with liver metastasis(12%) and a smaller number showed hormonal activity (11%). Prognosis improved markedly in patients who underwent surgical resection. Therefore, whenever appropriate, surgical resection should be the treatment of choice in patients with pNET.


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