Immunohistochemistry-based assessment of androgen receptor status and the AR-null phenotype in metastatic castrate resistant prostate cancer

Gupta, Sounak; Vanderbilt, Chad; Abida, Wassim; Fine, Samson W.; Tickoo, Satish K.; Al‐Ahmadie, Hikmat; Chen, Ying-Bei; Sirintrapun, S. Joseph; Chadalavada, Kalyani; Nanjangud, Gouri J.; Bialik, Ann; Morris, Michael J.; Scher, Howard I.; Ladanyi, Marc; Reuter, Victor E.; Gopalan, Anuradha

doi:10.1038/s41391-020-0214-6

Cited by 12 publications

(9 citation statements)

References 34 publications

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“…We evaluated p53 expression patterns in our PCa specimens as reported previously (Figure 1a,b). 20 In the untreated tumor specimens ( n = 274), 17.88% carried wild‐type TP53 while 1.46%, 30.29% and 50.37% showed TP53 mutation pattern 1, 2 and 3, respectively. In comparison, the majority of CRPC specimens displayed TP53 mutation pattern 3 (75%) while 8.33%, 5.56% and 11.11% showed wild‐type TP53 , TP53 mutation pattern 1 and 2, respectively ( n = 36 specimens), a mutation pattern distribution that was significantly different from the untreated PCa cohort ( p < 0.001; Figure 1b).…”

Section: Resultsmentioning

confidence: 93%

TP53 loss‐of‐function causes vulnerability to autophagy inhibition in aggressive prostate cancer

Zhang

Song

et al. 2022

Int J of Urology

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AbbreviationsADT = androgen deprivation therapy AR = androgen receptor ARGs = autophagy-related genes ARPs = autophagy-related proteins BPH = Benign prostatic hyperplasia CARNs = castration-resistant Nkx3.1-expressing cells CQ = Chloroquine CRPC = castration-resistant prostate cancer DMSO = dimethylsulfoxide GEM = genetically-engineered mouse MAPK = mitogen-activated protein kinase mCRPC = metastatic castrationresistant prostate cancer NEPC = neuroendocrine prostate cancer NPp53K = Nkx3.1 CreERT2/+ ; Pten flox/flox ; Trp53 flox/flox ; Kras lsl-G12D/+; R26R-lsl-YFP/+ pAkt = phospho-Akt PCa = prostate cancer pErk1/2 = phospho-Erk1/2 pFoxO3a = phospho-FoxO3a PRAD = prostate adenocarcinoma PSA = prostate-specific antigen TCGA = The Cancer Genome Atlas

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Section: Resultsmentioning

confidence: 93%

TP53 loss‐of‐function causes vulnerability to autophagy inhibition in aggressive prostate cancer

Zhang

Song

et al. 2022

Int J of Urology

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“…In patients with CRPC some authors have evaluated genetic alterations, particularly in RB1, PTEN, and p53 27,28 . Kaur et al have recently explored this issue in patients with NE differentiation, with high‐risk PCa, and in patients with mCRPC treated with ABI ore ENZA.…”

Section: Discussionmentioning

confidence: 99%

“…[23][24][25][26] In patients with CRPC some authors have evaluated genetic alterations, particularly in RB1, PTEN, and p53. 27,28 29 Moreover, the authors highlight the role of AR-low CGA-expressing cells that could predict resistance to neoadjuvant hormonal therapies. The present study opens some important insights into the management of these patients.…”

Section: Discussionmentioning

confidence: 99%

Serum levels of chromogranin are not predictive of poorly differentiated prostate cancer: Results from a multicenter radical prostatectomy cohort

et al. 2022

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Background Recently a possible link between elevated Chromogranin A (CgA) levels and poorly differentiated prostate cancer has been proposed. The aim of our study was to explore the association of CgA levels and the risk of poorly differentiated prostate cancer (PCa) in men undergoing radical retropubic prostatectomy (RRP). Materials and Methods From 2012 onwards, 335 consecutive men undergoing RRP for PCa at three centers in Italy were enrolled into a prospective database. Body mass index (BMI) was calculated before RRP. Blood samples were collected and tested for total prostate‐specific antigen (PSA) levels and chromogranin A (CgA). We evaluated the association between serum levels of CgA and upstaging and upgrading using logistic regression analyses. Results Median age and preoperative PSA levels were 65 years (interquartile range [IQR]: 60–69) and 7.2 ng/ml (IQR: 5.3–10.4), respectively. Median BMI was 26.1 kg/m2 (IQR: 24–29) with 56 (16%) obese (BMI ≥ 30 kg/m2). Median CgA levels were 51 (39/71). Overall, 129/335 (38,5%) presented an upstaging, and 99/335 (30%) presented an upgrading. CgA was not a predictor of upstaging or upgrading on RP. Conclusions In our multicenter cohort of patients, CgA is not a predictor of poorly differentiated PCa on radical prostatectomy. According to our experience, CgA should not be considered a reliable marker to predict poorly differentiated or advanced prostate cancer.

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“…For instance, AR expression by IHC is feasible and reproducible. The binary output of AR expression assessment (present or absent in nuclei of tumor cells) increases the reproducibility of the test between laboratories [ 111 ]. AR expression assessment may have a role in clinical practice for de-escalating therapy with androgen receptor signaling inhibitors and for the evaluation of alternative treatment options in refractory metastatic castration-resistant prostate cancer, although detection of AR mutations and amplifications on liquid biopsies have been associated to outcomes in more recent years, as stated before [ 29 ].…”

Section: Tissue and Methodsmentioning

confidence: 99%

Molecular Characterization of Prostate Cancers in the Precision Medicine Era

Giunta

Annaratone

Bollito

et al. 2021

Cancers

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Prostate cancer (PCa) therapy has been recently revolutionized by the approval of new therapeutic agents in the metastatic setting. However, the optimal therapeutic strategy in such patients should be individualized in the light of prognostic and predictive molecular factors, which have been recently studied: androgen receptor (AR) alterations, PTEN-PI3K-AKT pathway deregulation, homologous recombination deficiency (HRD), mismatch repair deficiency (MMRd), and tumor microenvironment (TME) modifications. In this review, we highlighted the clinical impact of prognostic and predictive molecular factors in PCa patients’ outcomes, identifying biologically distinct subtypes. We further analyzed the relevant methods to detect these factors, both on tissue, i.e., immunohistochemistry (IHC) and molecular tests, and blood, i.e., analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Moreover, we discussed the main pros and cons of such techniques, depicting their present and future roles in PCa management, throughout the precision medicine era.

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Immunohistochemistry-based assessment of androgen receptor status and the AR-null phenotype in metastatic castrate resistant prostate cancer

Cited by 12 publications

References 34 publications

TP53 loss‐of‐function causes vulnerability to autophagy inhibition in aggressive prostate cancer

TP53 loss‐of‐function causes vulnerability to autophagy inhibition in aggressive prostate cancer

Serum levels of chromogranin are not predictive of poorly differentiated prostate cancer: Results from a multicenter radical prostatectomy cohort

Molecular Characterization of Prostate Cancers in the Precision Medicine Era

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