Comprehensive analysis of serum chromogranin A and neuron‐specific enolase levels in localized and castration‐resistant prostate cancer

2020 ◽  
Vol 127 (1) ◽  
pp. 44-55 ◽  
Author(s):  
Tibor Szarvas ◽  
Anita Csizmarik ◽  
Tamás Fazekas ◽  
András Hüttl ◽  
Péter Nyirády ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromogranin A ◽  
Neuron Specific Enolase ◽  
Comprehensive Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Oligometastatic Prostate Adenocarcinoma. Clinical-Pathologic Study of a Histologically Under-Recognized Prostate Cancer

2020 ◽  
Vol 10 (4) ◽  
pp. 265 ◽  
Author(s):  
Claudia Manini ◽  
Alba González ◽  
David Büchser ◽  
Jorge García-Olaverri ◽  
Arantza Urresola ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Local Control ◽  
Chromogranin A ◽  
Prostate Adenocarcinoma ◽  
Fisher Exact Test ◽  
Castration Resistant Prostate Cancer ◽  
Ki 67 ◽  
Pgp 9.5 ◽  
Castration Resistant ◽  
Therapeutic Decisions

The clinical parameters and the histological and immunohistochemical findings of a prospective protocolized series of 27 prostate carcinoma patients with oligometastatic disease followed homogeneously were analyzed. Lymph nodes (81.5%) and bones (18.5%) were the only metastatic sites. Local control after metastatic directed treatment was achieved in 22 (81.5%) patients. A total of 8 (29.6%) patients developed castration-resistant prostate cancer. Seventeen (63%) patients presented with non-organ confined disease. The Gleason index 8–10 was the most frequently observed (12 cases, 44.4%) combined grade. Positive immunostainings were detected with androgen receptor (100%), PGP 9.5 (74%), ERG (40.7%), chromogranin A (29.6%), and synaptophysin (18.5%) antibodies. The Ki-67 index value > 5% was observed in 15% of the cases. L1CAM immunostaining was negative in all cases. Fisher exact test showed that successful local control of metastases was associated to mild inflammation, organ confined disease, Ki-67 index < 5%, and Gleason index 3 + 3. A castration resistant status was associated with severe inflammation, atrophy, a Gleason index higher than 3 + 3, Ki-67 index ≥ 5%, and positive PGP 9.5, chromogranin A, and synaptophysin immunostainings. In conclusion, oligometastatic prostate adenocarcinoma does not have a specific clinical-pathologic profile. However, some histologic and immunohistochemical parameters of routine use may help with making therapeutic decisions.

Circulating tumor cell (CTC) enumeration in patients with metastatic neuroendocrine prostate cancer (NEPC) and castration-resistant prostate cancer (CRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 204-204 ◽  
Author(s):  
Gurveen Kaur ◽  
Beerinder Singh ◽  
Himisha Beltran ◽  
Naveed Hassan Akhtar ◽  
David M. Nanus ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cell ◽  
Specific Antigen ◽  
Neuron Specific Enolase ◽  
Circulating Tumor Cell ◽  
Entire Group ◽  
Castration Resistant Prostate Cancer ◽  
Similar Frequency ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer

204 Background: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer. Circulating tumor cell (CTC) counts as measured by CellSearch are prognostic for large groups with metastatic prostate cancer (PC), but are not well described in NEPC. Methods: With institutional review board approval, we retrospectively identified patients with metastatic PC and available CTC enumeration (CellSearch methodology) and compared counts/7.5 mL blood and overall survival (OS), measured from the first recorded CTC count until death or last follow up. Entry criteria for clinical trials were used to define NEPC, including histology (small cell/neuroendocrine carcinoma or adenocarcinoma with more than 50% NE staining), serum chromogranin greater than 5x ULN and/or neuron specific enolase greater than 2x ULN, and/or predominant liver/brain metastases with lack of prostate-specific antigen [Beltran ASCO 2013, clinicaltrials.gov NCT01799278 ]. Frequency of detectable and unfavorable counts was tabulated and OS was compared across groups. Results: Sixty one patients were identified: 21 NEPC with median age 73.7 and 40 patients with castration-resistant prostate cancer (CRPC) with median age 73.9 over contemporary time periods 2009 to 2012. Median OS for the entire group was 22.6 months (mo), with a trend for shorter OS in NEPC (20.7 mo) than CRPC (22.7 mo), p=0.11. 47.6% of NEPC and 55% of CRPC had detectable CTC counts (p=0.58); 38.1% of NEPC and 40.0% of CRPC had greater than or equal to five CTCs (p=0.89). CTC counts of 0 to 4 versus greater than or equal to five were prognostic for both groups: NEPC with 0 to 4 CTCs had median OS of 22.6 versus 6.6 mo for CTCs greater than or equal to 5 (p<0.001) and CRPC with 0 to 4 CTCs median OS not reached (mean 40.6 mo) versus 11.2 mo for those with greater than or equal to five CTCs (p<0.001). Conclusions: Patients with NEPC have similar frequency of detectable and elevated CTC counts by CellSearch methodology as compared to an overall CRPC population. CTC counts are prognostic for both groups.

scholarly journals Prognostic role of chromogranin A in castration-resistant prostate cancer: A meta-analysis

2018 ◽  
Vol 20 (6) ◽  
pp. 561 ◽  
Author(s):  
Xue-Song Li ◽  
Li-Qun Zhou ◽  
Peng Hong ◽  
Run-Qi Guo ◽  
Gang Song ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromogranin A ◽  
Meta Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Prognostic Role ◽  
Castration Resistant

scholarly journals Serum chromogranin-A-based prognosis in metastatic castration-resistant prostate cancer

2018 ◽  
Vol 21 (3) ◽  
pp. 431-437 ◽  
Author(s):  
Karthik V. Giridhar ◽  
Cristobal Sanhueza ◽  
David W Hillman ◽  
Hassan Alkhateeb ◽  
Rachel Carlson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromogranin A ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals A testosterone metabolite 19-hydroxyandrostenedione induces neuroendocrine trans-differentiation of prostate cancer cells via an ectopic olfactory receptor

2018 ◽  
Author(s):  
Tatjana Abaffy ◽  
James R. Bain ◽  
Michael J. Muehlbauer ◽  
Ivan Spasojevic ◽  
Shweta Lodha ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
G Protein ◽  
Olfactory Receptor ◽  
Neuron Specific Enolase ◽  
Receptor Activation ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Castration Resistant ◽  
Protein Receptor

AbstractOlfactory receptor OR51E2, also known as a Prostate Specific G-Protein Receptor, is highly expressed in prostate cancer but its function is not well understood. Through in silico and in vitro analyses, we identified 24 agonists and 1 antagonist for this receptor. We detected that agonist 19-hydroxyandrostenedione, a product of the aromatase reaction, is endogenously produced upon receptor activation. We characterized the effects of receptor activation on metabolism using a prostate cancer cell line and demonstrated decreased intracellular anabolic signals and cell viability, induction of cell cycle arrest, and increased expression of neuronal markers. Furthermore, upregulation of neuron-specific enolase by agonist treatment was abolished in OR51E2-KO cells. The results of our study suggest that OR51E2 activation results in neuroendocrine trans-differentiation. These findings reveal a new role for OR51E2 and establish this G-protein coupled receptor as a novel therapeutic target in the treatment of prostate cancer.SignificanceProstate cancer is the second most common cancer in men. Most deaths from prostate cancer are due to the progression of localized disease into metastatic, castration-resistant prostate cancer characterized by increased number of neuroendocrine-like cells. These neuroendocrine-like cells are non-proliferating, terminally differentiated cells. Olfactory receptor OR51E2, also known as a Prostate Specific G-Protein Receptor, is highly expressed in prostate cancer, and its expression correlates with disease progression. Here, we identify and validate novel endogenous ligands for this receptor. We show that activation of OR51E2 by newly-discovered prostate cancer-relevant agonists facilitates cellular transformation, resulting in neuroendocrine trans-differentiation, a characteristic phenotype of castrate resistant prostate cancer. Our results establish this G-protein coupled receptor as a novel and therapeutic target for castration-resistant prostate cancer.HighlightsDiscovery of novel agonists for olfactory receptor OR51E2/PSGR highly relevant to prostate cancer pathologyActivation of OR51E2 receptor by agonist N-acetyl-N-formyl-5-methoxykynurenamine (AFMK) results in release of 19-hydroxyandrostenedione (19-OH AD) from the prostate cancer cells indicating its endogenous productionActivation of OR51E2 receptor by 19-OH AD, AFMK, and propionic acid decreases anabolic and proliferative signalsActivation of OR51E2 receptor by 19-OH AD and AFMK increases markers specific for neuroendocrine trans-differentiation (NEtD)Ablation of the OR51E2 gene in prostate cancer cells treated with agonist 19-OH AD significantly reduces neuron-specific enolase

scholarly journals Chromogranin A predicts outcome in prostate cancer patients treated with abiraterone

2014 ◽  
Vol 21 (3) ◽  
pp. 487-493 ◽  
Author(s):  
Salvatore Luca Burgio ◽  
Vincenza Conteduca ◽  
Cecilia Menna ◽  
Elisa Carretta ◽  
Lorena Rossi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromogranin A ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Psa Response ◽  
Group A ◽  
Group 3 ◽  
Group B

In this retrospective study, we evaluated the chromogranin A (CgA) baseline value as a predictor of clinical outcome in patients with metastatic castration-resistant prostate cancer (CRPC) treated with abiraterone 1000 mg per day, whose disease progressed after docetaxel chemotherapy. In the 48 evaluable patients, serum CgA level was normal when <120 ng/ml (group A, n=16), within three times the upper normal value (UNV) when between 120 and 360 (group B, n=16), more than three times the UNV when ≥360 ng/ml (group C, n=16). Decline in PSA level ≥50% or more (PSA RR) was observed in 26 of 48 (54%) patients. PSA response rate did not correlate with the CgA groups. CgA levels more than three times the UNV predicted an early radiological progressive disease in eight of 11 cases (73%). The median progression-free survival (PFS) among the CgA groups A, B, and C was 9.2, 9.2, and 4.8 months respectively, P=0.0459. The median overall survival (OS) among the CgA groups was 19.0, 18.8, and 10.8 months respectively, P=0.2092. In the multivariate analysis, PSA RR (nonresponsive vs responsive) and CgA levels (group 3 vs groups 1+2) were predictors of PFS (P=0.0002 and P=0.0047 respectively), whereas PSA RR only was significantly associated with OS (P=0.0024), while CgA levels remained of borderline significance (P=0.0919). A serum CGA level more than three times the UNV predicted PFS and showed a trend vs OS prediction, independently from PSA response, in CRPC patients treated with abiraterone.

scholarly journals Effect of abiraterone combined with prednisone on serum CgA and NSE in metastatic castration-resistant prostate cancer without previous chemotherapy

2021 ◽  
Vol 18 (3) ◽  
pp. 631-637
Author(s):  
Ke Yang ◽  
Tieqiu Li ◽  
Zhiyong Gao ◽  
Weiwei Zhang
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Neuron Specific Enolase ◽  
Progression Free Survival ◽  
Control Group ◽  
Study Group ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

Purpose: To investigate the influence of a combination of abiraterone and prednisone on serum chromogranin A (CgA) and neuron-specific enolase (NSE) in patients with metastatic castrationresistant prostate cancer (mCRPC) without previous chemotherapy, so as to provide reference data for drug therapy of prostate cancer. Methods: A total of 103 mCRPC patients without chemotherapy from January 2013 to March 2017 were included in this retrospective study. Seventy-one (71) patients received prednisone combined with abiraterone (study group), while 32 patients accepted prednisone (control group). The CgA, NSE and prostate-specific antigen (PSA) in the two groups were monitored, while PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS) were determined during follow-up. Results: PSA-PFS, rPFS and OS in the study group were significantly higher than those in the control group (p < 0.05). The increased proportion of CgA or NSE in the study group was significantly lower than that in the control group at 6 months of treatment (p < 0.05). The occurrences of NED before treatment and 6 months after treatment were both independent predictors of PSA and radiographic progression in the study group (p < 0.05). Conclusion: The combination of prednisone and abiraterone is helpful for prognosis in mCRPC patients that are not on chemotherapy. The occurrence of NED predicts mostly poor prognosis of mCRPC patients on a combination of abiraterone and prednisone

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