Androgen Receptor Gene Copy Number and Protein Expression in Treatment-Naïve Prostate Cancer

2017 ◽  
Vol 99 (2) ◽  
pp. 222-228 ◽  
Author(s):  
Filip Poelaert ◽  
Candy Kumps ◽  
Nicolaas Lumen ◽  
Stephanie Verschuere ◽  
Louis Libbrecht ◽  
...  
2014 ◽  
Vol 54 (9) ◽  
pp. 900-907 ◽  
Author(s):  
Lisha Wang ◽  
Sean R. Williamson ◽  
Shaobo Zhang ◽  
Jiaoti Huang ◽  
Rodolfo Montironi ◽  
...  

2021 ◽  
Author(s):  
Anna Cremonini ◽  
Luca Saragoni ◽  
Luca Morandi ◽  
Angelo G. Corradini ◽  
Caterina Ravaioli ◽  
...  

AbstractCarcinomas with apocrine differentiation (CAD) of the breast are rare tumours typically presenting high immunohistochemical expression of androgen receptor (AR) which is a target molecule for personalised therapy. To date, no studies have evaluated the genetic changes that are associated with AR immunohistochemical expression in CADs. The present work aims to characterise AR status in CADs. Twenty CAD tumours were studied with immunohistochemistry, in situ fluorescence hybridization and DNA methylation analysis, to evaluate AR expression and its regulator status. All tumours demonstrated high AR immunohistochemical expression, with over 95% of the neoplastic cells showing AR positivity in 19/20 cases. CADs showed AR gene copy loss in a percentage of neoplastic cells ranging from 5 to 84% (mean 48.93%). AR regulator genes, including the MAGE family, UXT and FLNA, presented variable methylation levels, but were mainly hypomethylated and therefore all transcriptionally active. The results of this study indicate that CADs present AR monosomy, paralleled by higher transcriptional activity of the gene with potential to influence response to AR deprivation therapy.


2003 ◽  
Vol 170 (5) ◽  
pp. 1817-1821 ◽  
Author(s):  
O. HARRIS FORD ◽  
CHRISTOPHER W. GREGORY ◽  
DESOK KIM ◽  
ANDREW B. SMITHERMAN ◽  
JAMES L. MOHLER

2013 ◽  
Vol 20 (3) ◽  
pp. 403-413 ◽  
Author(s):  
Tobias Zellweger ◽  
Susanne Stürm ◽  
Silvia Rey ◽  
Inti Zlobec ◽  
Joel R Gsponer ◽  
...  

Patients with advanced prostate cancer (PC) are usually treated with androgen withdrawal. While this therapy is initially effective, nearly all PCs become refractory to it. As hormone receptors play a crucial role in this process, we constructed a tissue microarray consisting of PC samples from 107 hormone-naïve (HN) and 101 castration-resistant (CR) PC patients and analyzed the androgen receptor (AR) gene copy number and the protein expression profiles of AR, Serin210-phosphorylated AR (pAR210), estrogen receptor (ER)β, ERα and the proliferation marker Ki67. The amplification of the AR gene was virtually restricted to CR PC and was significantly associated with increased AR protein expression (P<0.0001) and higher tumor cell proliferation (P=0.001). Strong AR expression was observed in a subgroup of HN PC patients with an adverse prognosis. In contrast, the absence of AR expression in CR PC was significantly associated with a poor overall survival. While pAR210 was predominantly found in CR PC patients (P<0.0001), pAR210 positivity was observed in a subgroup of HN PC patients with a poor survival (P<0.05). Epithelial ERα expression was restricted to CR PC cells (9%). ERβ protein expression was found in 38% of both HN and CR PCs, but was elevated in matched CR PC specimens. Similar to pAR210, the presence of ERβ in HN patients was significantly associated with an adverse prognosis (P<0.005). Our results strongly suggest a major role for pAR210 and ERβ in HN PC. The expression of these markers might be directly involved in CR tumor growth.


2010 ◽  
Vol 28 (13) ◽  
pp. 2174-2180 ◽  
Author(s):  
Rafal Dziadziuszko ◽  
Daniel T. Merrick ◽  
Samir E. Witta ◽  
Adelita D. Mendoza ◽  
Barbara Szostakiewicz ◽  
...  

PurposeThe purpose of this study was to characterize insulin-like growth factor-1 receptor (IGF1R) protein expression, mRNA expression, and gene copy number in surgically resected non–small-cell lung cancers (NSCLC) in relation to epidermal growth factor receptor (EGFR) protein expression, patient characteristics, and prognosis.Patients and MethodsOne hundred eighty-nine patients with NSCLC who underwent curative pulmonary resection were studied (median follow-up, 5.3 years). IGF1R protein expression was evaluated by immunohistochemistry (IHC) with two anti-IGF1R antibodies (n = 179). EGFR protein expression was assessed with PharmDx kit. IGF1R gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 114 corresponding fresh-frozen samples. IGF1R gene copy number was assessed by fluorescent in situ hybridization using customized probes (n = 181).ResultsIGF1R IHC score was higher in squamous cell carcinomas versus other histologies (P < .001) and associated with stage (P = .03) but not survival (P = .46). IGF1R and EGFR protein expression showed significant correlation (r = 0.30; P < .001). IGF1R gene expression by qRT-PCR was higher in squamous cell versus other histologies (P = .006) and did not associate with other clinical features nor survival (P = .73). Employing criteria previously established for EGFR copy number, patients with IGF1R amplification/high polysomy (n = 48; 27%) had 3-year survival of 58%, patients with low polysomy (n = 87; 48%) had 3-year survival of 47% and patients with trisomy/disomy (n = 46; 25%) had 3-year survival of 35%, respectively (P = .024). Prognostic value of high IGF1R gene copy number was confirmed in multivariate analysis.ConclusionIGF1R protein expression is higher in squamous cell versus other histologies and correlates with EGFR expression. IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number harbors positive prognostic value.


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