Current Histopathologic and Molecular Characterisations of Prostate Cancer: Towards Individualised Prognosis and Therapies

Santoni, Matteo; Scarpelli, Marina; Mazzucchelli, Roberta; López-Beltrán, Antonio; Liu, Cheng; Epstein, Jonathan I.; Cascinu, Stefano; Briganti, Alberto; Catto, James W.F.; Montorsi, Francesco; Montironi, Rodolfo

doi:10.1016/j.eururo.2015.05.041

Cited by 19 publications

(8 citation statements)

References 29 publications

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“…Prostate cancer (PCa) is one of the leading causes of cancer-related death worldwide, accounting for 180,890 new cases and over 26,000 deaths in the United States in 2016 [62]. The last two decades have been characterized by fundamental improvements of our knowledge on the complexity of prostate carcinogenesis [63,64,65]. This process is the result of a series of events that involves: (1) wide simultaneous genomic rearrangements leading to double-strand DNA breaks (a phenomenon known as “chromoplexy”) [66]; (2) metabolic alterations (including over-expression of major lipogenic enzymes such as FASN and HMG-CoA reductase) and deregulation of the energy sensor 5-AMP-activated protein kinase, AMPK) [67]; (3) immune cells, in particular neutrophils and tumor associated macrophages (TAMs) [68,69,70], which contribute to the creation of a favorable microenvironment for PCa growth and invasion; (4) neuroendocrine cells, defined by the presence in the cytoplasm of markers such as chromogranin A (CgA) and neuron-specific enolase (NSE), implicated in PCa aggressiveness [71,72]; (5) changes in human urinary microbiota [73], which may result relevant in PCa carcinogenesis and response to therapy.…”

Section: Obesity and Prostate Cancermentioning

confidence: 99%

Key Role of Obesity in Genitourinary Tumors with Emphasis on Urothelial and Prostate Cancers

Santoni

Cimadamore

Massari

et al. 2019

Cancers

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Background: In human populations, a certain amount of data correlate obesity/body mass index (BMI) with urothelial cancer (UC) and prostate cancer (PCa) occurrence, however this is not fully elucidated at all stages of disease. In an attempt to shed light on uncertain areas in such field, in the present review we illustrate the main molecular mechanisms linking obesity and cancer, focusing on the correlation between obesity and tumor risk, disease progression and response to chemo- and immunotherapy in patients with UC and the predictive/prognostic role of obesity in PCa patients treated with the currently available therapeutic approaches. Methods: We did a large-scale literature search on existing scientific websites focusing on keywords “obesity”, “body mass index (BMI)”, “urothelial cancer”, “prostate cancer”, “docetaxel”, “cabazitaxel”, “abiraterone acetate”, “enzalutamide”, and “radium223”. Results: Many adipocytes-induced molecules support tumor proliferation through activation of various cellular pathways. The available evidence in the postoperative setting do the role of BMI in oncological outcomes prediction still not completely clear. Likewise, in metastatic UC patients controversial results link the role of obesity/BMI with clinical outcomes of tumor response to chemotherapy. Adipose stromal cells recruitment, induced by PCa cells, from white adipose tissue to the tumor sites inducing cell invasiveness was associated with poor survival. Conflicting data, although more oriented towards a better survival outcome, resulted in obese patients treated with docetaxel. In PCa cell-lines a certain cabazitaxel chemo resistance adipose stromal cells (ASC)-mediated was demonstrated. In metastatic castration-resistant PCa patients with high BMI (>25 kg/m2) receiving abiraterone acetate there were significant worse survival outcomes, while in enzalutamide patients BMI did not affect survival outcome. In radium 223 patients higher BMI significantly correlated with favorable overall survival. Conclusions: The main focus of this review was to understand the interplay between obesity/BMI and UC/PCa. Several pathogenic cellular pathways exploring the issue are discussed, opening the way to challenging tailored treatments on the basis of BMI. Improving the knowledge of molecular connections between obesity and UC and PCa could favor the development of new therapies likely reducing chemo- and immunotherapy drug resistance.

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Section: Obesity and Prostate Cancermentioning

confidence: 99%

Key Role of Obesity in Genitourinary Tumors with Emphasis on Urothelial and Prostate Cancers

Santoni

Cimadamore

Massari

et al. 2019

Cancers

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“…Of these features, grade remains to be the most robust and well-studied parameter in prostate cancer where a direct association is seen between increasing GSs and biochemical failure with local and distant recurrence in both untreated and treated patients. 17 18 …”

Section: Discussionmentioning

confidence: 99%

Prostate cancer

Grageda¹,

Choy

Paner³

et al. 2021

Asian Journal of Andrology

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Lower incidence and mortality rates from prostate cancer (PCa) have been shown in Asian men in general compared to Westerners. This is the first study detailing the clinicopathologic features of resected prostate cancer in Filipino men living in the Philippines (PH). This study investigated the supposed “lower risk” Filipino and “higher risk” American PCa patients from the PH and the United States of America (USA), respectively. We examined 348 (176 from PH, 172 from USA) radical prostatectomy cases. The clinicopathologic features of both groups (age at time of diagnosis, preoperative prostate-specific antigen [pre-op PSA] level, Gleason score [GS], Grade groups [GG], margin involvement, extraprostatic extension [EPE], seminal vesicle invasion [SVI], and regional lymph node [RLN] metastasis) were compared. Six of seven prognosticators examined were more strongly associated with Filipinos than with Americans. Filipinos were older at diagnosis (PH: 64.32 ± 6.56 years vs USA: 58.98 ± 8.08 years) and had higher pre-op PSA levels (PH: 21.39 ± 46.40 ng ml −1 vs USA: 7.63 ± 9.19 ng ml −1 ). Filipino men had more advanced grade, GG 2 with minor pattern 5 (PH: 6.2% vs USA: 2.9%) and GG 5 (PH: 14.8% vs USA: 3.5%). Likewise, other adverse pathological features in margin positivity (PH: 52.3% vs USA: 23.8%), focal EPE (PH: 14.2% vs USA: 2.3%), and SVI (PH: 17.1% vs USA: 5.8%) were more commonly observed in Filipinos. This study reveals the prognostic disadvantage of Filipinos versus Americans and highlights an important difference of Filipinos from other studied Asian ethnicities that have repeatedly been shown to have lower-risk PCa. This study, the first on Filipino PCa patients with RP, suggests the need to modify Western-based risk stratification when employed in other countries like the PH.

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“…The mechanism and treatment of metastatic PCa have been the focus of targeted therapy as a new treatment with great application prospects. Santoni et al indicated that fully understanding the role of TMPRSS2-ERG is important for individualised therapy in PCa patients (11). urbinati et al designed a kind of siRNA anti-TMPRSS2-ERG and successfully downregulated the expression of this fusion gene, and observably inhibited the proliferation of PCa cells (12).…”

Section: Discussionmentioning

confidence: 99%

Identification of TMPRSS2-ERG mechanisms in prostate cancer invasiveness: Involvement of MMP-9 and plexin B1

Liu

Huang

et al. 2016

Oncology Reports

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The relationship of TMPRSS2-ERG fusion gene with matrix metalloproteinase-9 (MMP-9) and PLXNB1 (plexin B1) in regulation of prostate cancer (PCa) aggressiveness was investigated. Fluorescence in situ hybridization (FISH) assays, qRT-PCR and western blot analysis were employed to detect the expression of TMPRSS2-ERG fusion gene, ERG, MMP-9 and PLXNB1 of 135 human tissues, which included 55 metastatic PCa cases, 50 localized PCa cases and 30 BPH cases. Then using siRNA (anti-ERG, MMP-9 and PLXNB1, respectively) downregulation of the target gene of VCaP and PC-3 cells, MTT and Transwell were performed. The results showed that the positive rate of TMPRSS2-ERG fusion was 38.1% (40/105) in total PCa samples, 47.3% (26/55) of metastatic PCa, 28.0% (14/50) of localized PCa, while 0.0% (0/30) in BPH samples. The mRNA and protein expression of ERG, MMP-9 and PLXNB1 were higher in metastatic PCa (P<0.0001), and the mRNA expression of the three genes were positively correlated with TMPRSS2-ERG fusionin PCa group (P<0.0001). siRNA transfected PCa cells can effectively downregulate the target gene expression, and we identified that MMP-9 and PLXNB1 expression were all regulated by TMPRSS2-ERG fusion gene. While only PLXNB1 contributed to TMPRSS2-ERG mediated enhancements of VCaP cell migration and invasion. The results demonstrated that PLXNB1, but not MMP-9, was the target gene directly related to TMPRSS2-ERG in PCa cell migration and invasion.

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Current Histopathologic and Molecular Characterisations of Prostate Cancer: Towards Individualised Prognosis and Therapies

Cited by 19 publications

References 29 publications

Key Role of Obesity in Genitourinary Tumors with Emphasis on Urothelial and Prostate Cancers

Key Role of Obesity in Genitourinary Tumors with Emphasis on Urothelial and Prostate Cancers

Prostate cancer

Identification of TMPRSS2-ERG mechanisms in prostate cancer invasiveness: Involvement of MMP-9 and plexin B1

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