Hormones & Cancer最新文献

{"title":"Effects of Ketoconazole on ACTH-Producing and Non-ACTH-Producing Neuroendocrine Tumor Cells.","authors":"Aura D Herrera-Martínez,&nbsp;Richard A Feelders,&nbsp;Wouter W de Herder,&nbsp;Justo P Castaño,&nbsp;María Ángeles Gálvez Moreno,&nbsp;Fadime Dogan,&nbsp;Rosanna van Dungen,&nbsp;Peter van Koetsveld,&nbsp;Leo J Hofland","doi":"10.1007/s12672-019-00361-6","DOIUrl":"https://doi.org/10.1007/s12672-019-00361-6","url":null,"abstract":"<p><p>Prolonged remission of hypercortisolism with steroidogenesis inhibitors has been described in patients with ectopic adrenocorticotropic hormone (ACTH) syndrome. The anti-proliferative and pro-apoptotic effect of ketoconazole in human cancer cells was previously suggested. The aim of this study was to explore the effects of ketoconazole on ACTH-producing and non-ACTH-producing neuroendocrine tumor (NET) cell lines. The effects of ketoconazole alone, and in combination with somatostatin analogs, were evaluated in two human cell lines: DMS-79 (ectopic ACTH-producing small cell lung carcinoma) and BON-1 (human pancreatic NET). Total DNA measurement, apoptosis, cell cycle, chromogranin A (CgA)/proopiomelanocortin (POMC) expression by qRT-PCR, serotonin, CgA, and ACTH secretion assays were performed. In both cell lines, ketoconazole significantly suppressed cell growth and colony formation in a dose and time-dependent manner. The effect in DMS-79 was primarily cytotoxic, while it was more apoptotic in BON-1 cells. Ketoconazole also induced increase in G0/G1 phase in both cell lines and arrest in phase G2/M of BON-1 cells. Ketoconazole did not affect the secretion of serotonin, CgA, ACTH, or the mRNA expression of CgA and POMC. Decreased serotonin secretion was observed after the combination treatment with pasireotide. These results suggest a direct effect of ketoconazole on cell proliferation, apoptosis, and cell cycle in both ACTH- and non-ACTH-producing NET cells.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"10 2-3","pages":"107-119"},"PeriodicalIF":3.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-019-00361-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Estrogen in Androgen-Induced Prostate Carcinogenesis in NBL Rats.","authors":"Nur Ozten,&nbsp;Katherine Vega,&nbsp;Joachim Liehr,&nbsp;Xi Huang,&nbsp;Lori Horton,&nbsp;Ercole L Cavalieri,&nbsp;Eleanor G Rogan,&nbsp;Maarten C Bosland","doi":"10.1007/s12672-019-00360-7","DOIUrl":"https://doi.org/10.1007/s12672-019-00360-7","url":null,"abstract":"<p><p>Androgens are thought to cause prostate cancer, but the underlying mechanisms are unclear. Data from animal studies suggest that for androgens to cause prostate cancer, they must be aromatized to estrogen and act in concert with estrogen metabolites. We tested the hypothesis that androgen-receptor and estrogen receptor-mediated effects of androgen and estrogen are necessary, as well as genotoxicity of estrogen metabolites. NBL rats were treated with androgenic and estrogenic compounds for 16-75 weeks through slow-release silastic implants or pellets. Testosterone alone induced cancer in the prostate of 37% of rats. 5α-Dihydrotestosterone, which cannot be converted to estradiol or testosterone, did not cause a significant prostate cancer incidence (4%). Addition of estradiol to 5α-dihydrotestosterone treatment did not markedly enhance prostate cancer incidence (14%), unlike adding estradiol to testosterone treatment which induced a 100% tumor incidence. Testosterone plus estradiol treatment induced a DNA adduct detectable by ³²P-postlabeling, oxidative DNA damage (8-hydroxyguanosine), and lipid peroxidation at the site within the prostate where this treatment causes cancers, preceding later cancer formation. The non-estrogenic 4-hydroxy metabolite of estradiol, when combined with testosterone, induced prostatic dysplasia within 16 weeks and, after long-term treatment, a very low incidence of prostate cancer (21%). When an estrogen that cannot be hydroxylated (2-fluoroestradiol) was added to this combined treatment with testosterone and 4-hydroxyestradiol, dysplasia frequency after 16 weeks was doubled. These results strongly support the hypothesis, but additional definitive studies are needed which may identify new targets to interfere with these mechanisms that are clinically feasible in humans.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"77-88"},"PeriodicalIF":3.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-019-00360-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37061628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploratory Analysis of Plasma Neurotensin as a Novel Biomarker for Early Detection of Colorectal Polyp and Cancer.","authors":"Shengyang Qiu,&nbsp;Stella Nikolaou,&nbsp;Francesca Fiorentino,&nbsp;Shahnawaz Rasheed,&nbsp;Ara Darzi,&nbsp;David Cunningham,&nbsp;Paris Tekkis,&nbsp;Christos Kontovounisios","doi":"10.1007/s12672-019-00364-3","DOIUrl":"https://doi.org/10.1007/s12672-019-00364-3","url":null,"abstract":"<p><p>Earlier detection of colorectal cancer (CRC) results in improved survival. Existing non-invasive biomarkers have suboptimal accuracy. Neurotensin (NTS) is involved in CRC carcinogenesis. This study evaluated the diagnostic potential of plasma NTS for colorectal polyps and cancers. Participants were selected based on national CRC referral guidelines. All subjects underwent colonoscopy. Average plasma concentrations were compared across different diagnostic groups. Predictors for detecting colorectal neoplasia were identified. Receiver operator characteristic (ROC) curve analysis assessed the diagnostic accuracy of NTS. An independent biobank was used as validation group. Of 165 participants, 46 had polyps or CRC. Significantly higher plasma NTS was found in the colonic neoplasia group (603.6 pg/ml vs. 407.2 pg/ml, p < 0.01). Risk factors for colonic polyps or cancers included Log_e (plasma NTS concentration) (OR, 2.73; 95% CI, 1.33-5.59, p < 0.01), log_e (Age) (OR, 15.49; 95% CI, 2.67-89.66, p < 0.01) and cigarette smoking (OR, 3.49; 95% CI, 1.31-9.26, p = 0.01). Plasma NTS had an optimal sensitivity of 60.4% and specificity of 71.6% for the diagnosis of colorectal polyps and cancers. Similar diagnostic accuracy was obtained in the validation group. Plasma NTS has the potential to be a non-invasive biomarker for colorectal neoplasia. It appears to be more accurate than existing blood markers and is unique in being able to detect precancerous polyps.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"10 2-3","pages":"128-135"},"PeriodicalIF":3.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-019-00364-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9850009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen Signaling in Endometrial Cancer: a Key Oncogenic Pathway with Several Open Questions.","authors":"Adriana C Rodriguez,&nbsp;Zannel Blanchard,&nbsp;Kathryn A Maurer,&nbsp;Jason Gertz","doi":"10.1007/s12672-019-0358-9","DOIUrl":"https://doi.org/10.1007/s12672-019-0358-9","url":null,"abstract":"<p><p>Endometrial cancer is the most common gynecological cancer in the developed world, and it is one of the few cancer types that is becoming more prevalent and leading to more deaths in the USA each year. The majority of endometrial tumors are considered to be hormonally driven, where estrogen signaling through estrogen receptor α (ER) acts as an oncogenic signal. The major risk factors and some treatment options for endometrial cancer patients emphasize a key role for estrogen signaling in the disease. Despite the strong connections between estrogen signaling and endometrial cancer, important molecular aspects of ER function remain poorly understood; however, progress is being made in our understanding of estrogen signaling in endometrial cancer. Here, we discuss the evidence for the importance of estrogen signaling in endometrial cancer, details of the endometrial cancer-specific actions of ER, and open questions surrounding estrogen signaling in endometrial cancer.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"10 2-3","pages":"51-63"},"PeriodicalIF":3.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-019-0358-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Use of Oral Contraceptives and Risk of Luminal B, Triple-Negative, and HER2-Overexpressing Breast Cancer.","authors":"Nicole C Lorona, Linda S Cook, Mei-Tzu C Tang, Deirdre A Hill, Charles L Wiggins, Christopher I Li","doi":"10.1007/s12672-019-00362-5","DOIUrl":"10.1007/s12672-019-00362-5","url":null,"abstract":"<p><p>Oral contraceptive use is a well-established risk factor for breast cancer and is common among reproductive-aged women in the USA. Its relationship with less common, more aggressive, molecular subtypes is less clear. A population-based case-case analysis was conducted comparing three less common molecular subtypes to luminal A breast cancer among 1701 premenopausal cases aged 21-49 diagnosed with a first primary invasive breast cancer between 2004 and 2015. Medical record reviews and structured interviewer-administered questionnaires were used to collect data on oral contraceptive use. Multinomial logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for recency of oral contraceptive use for each subtype of breast cancer. Current use of oral contraceptives and use within 5 years before diagnosis was associated with lower odds of H2E tumors compared with luminal A tumors [OR = 0.5, 95% CI: 0.3, 0.9 and OR = 0.5, 95% CI: 0.4, 0.8, respectively] with increasing duration associated with decreasing odds (p for trend < 0.05). Oral contraceptive use was not associated with risks of TN or luminal B breast cancer. Oral contraceptive use may be more strongly positively associated with risks of luminal A, luminal B, and TN breast cancer than with risk of H2E tumors. These findings contribute to the etiological understanding of different molecular subtypes of breast cancer.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"71-76"},"PeriodicalIF":3.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6550997/pdf/12672_2019_Article_362.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37319795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of Aryl Hydrocarbon Receptor in L-Kynurenine-Mediated Parathyroid Hormone-Related Peptide Expression.","authors":"Zhiqing Duan,&nbsp;Jiangong Lu","doi":"10.1007/s12672-019-0357-x","DOIUrl":"https://doi.org/10.1007/s12672-019-0357-x","url":null,"abstract":"<p><p>Parathyroid hormone-related peptide (PTHrP), produced by specific cancers such as lung cancer, profoundly influences the formation of bone metastatic lesions via the \"vicious cycle\" of tumor growth and bone resorption. The changes in gene expression regulated by the abnormal microenvironment components play key roles in maintaining the biological characteristics of cells, such as the organotropism of cancer metastasis. A recent study has shown that L-kynurenine (L-Kyn), one of microenvironment components, induced a substantial increase in the metastasis of lung cancer cells. What remains unclear, however, is the linkage between L-Kyn and bone metastatic lesions. In the present paper, we found that a significant upregulation of PTHrP expression was detected when 95D cells, a lung cancer cell line, were incubated with 50 μM of L-Kyn. Meanwhile, L-Kyn (50/100 μM) strongly strengthened aryl hydrocarbon receptor (Ahr) expression. Additionally, L-Kyn (50 μM) increased the expression of the nuclear translocation of Ahr and cytochrome P450 1A1. Most importantly, the L-Kyn-induced upregulation of migration was significantly reduced when cells were co-incubated with siRNA_Ahr. Notably, the L-Kyn-mediated increase in PTHrP was also substantially attenuated upon siRNA_Ahr treatment in 95D cells. These results suggest that Ahr is involved in the L-Kyn-induced enhancement of PTHrP expression.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"10 2-3","pages":"89-96"},"PeriodicalIF":3.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-019-0357-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear ErbB-2: a Novel Therapeutic Target in ErbB-2-Positive Breast Cancer?","authors":"Rosalía I Cordo Russo,&nbsp;María F Chervo,&nbsp;Santiago Madera,&nbsp;Eduardo H Charreau,&nbsp;Patricia V Elizalde","doi":"10.1007/s12672-018-0356-3","DOIUrl":"https://doi.org/10.1007/s12672-018-0356-3","url":null,"abstract":"<p><p>Membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbB family of receptor tyrosine kinases, occurs in 15-20% of breast cancers (BC) and constitutes a therapeutic target in this BC subtype (ErbB-2-positive). Although MErbB-2-targeted therapies have significantly improved patients' clinical outcome, resistance to available drugs is still a major issue in the clinic. Lack of accurate biomarkers for predicting responses to anti-ErbB-2 drugs at the time of diagnosis is also an important unresolved issue. Hence, a better understanding of the ErbB-2 signaling pathway constitutes a critical task in the battle against BC. In its canonical mechanism of action, MErbB-2 activates downstream signaling pathways, which transduce its proliferative effects in BC. The dogma of ErbB-2 mechanism of action has been challenged by the demonstration that MErbB-2 migrates to the nucleus, where it acts as a transcriptional regulator. Accumulating findings demonstrate that nuclear ErbB-2 (NErbB-2) is involved in BC growth and metastasis. Emerging evidence also reveal a role of NErbB-2 in the response to available anti-MErbB-2 agents. Here, we will review NErbB-2 function in BC and will particularly discuss the role of NErbB-2 as a novel target for therapy in ErbB-2-positive BC.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"10 2-3","pages":"64-70"},"PeriodicalIF":3.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0356-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9901709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cabergoline Withdrawal Before and After Menopause: Outcomes in Microprolactinomas.","authors":"Rita Indirli,&nbsp;Emanuele Ferrante,&nbsp;Elisa Sala,&nbsp;Claudia Giavoli,&nbsp;Giovanna Mantovani,&nbsp;Maura Arosio","doi":"10.1007/s12672-019-00363-4","DOIUrl":"https://doi.org/10.1007/s12672-019-00363-4","url":null,"abstract":"<p><p>Natural course of prolactinomas after menopause is not fully elucidated. The aim of this study was to compare recurrence rate after cabergoline withdrawal in premenopausal vs. postmenopausal women with microprolactinoma. Sixty-two women with microprolactinoma treated with cabergoline for at least 1 year and followed for 2 years after drug withdrawal were retrospectively selected. Patients were divided into two groups: 48 patients stopped cabergoline before menopause (\"PRE\" group), while 14 after menopause (\"POST\" group). Recurrence was defined by prolactin levels above normal, confirmed on two occasions. Overall, 39/62 women relapsed. Patients who relapsed apparently had higher prolactin before withdrawal (median 216.2, range 21.2-464.3 mIU/L) compared with those in long-term remission (94.3, 29.7-402.8 mIU/L; p < 0.05), and the risk of recurrence seemed lower in POST women (4/14, 29%) than in PRE ones (35/48, 73%, p < 0.005, OR 0.149, 95% CI 0.040-0.558). However, none of the factors (prolactin before withdrawal, menopausal status, treatment duration, complete adenoma regression) showed a correlation with recurrence risk in multivariate analysis. The best strategy able to optimize CBG treatment and withdrawal's outcomes is still to be defined in microprolactinomas. Postmenopausal status cannot reliably predict long-term remission, and follow-up is needed also in women of this age.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"10 2-3","pages":"120-127"},"PeriodicalIF":3.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-019-00363-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9847756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Combination of RET, BRAF and Demographic Data Identifies Subsets of Patients with Aggressive Papillary Thyroid Cancer.","authors":"Jose R W Martínez,&nbsp;Sergio Vargas-Salas,&nbsp;Soledad Urra Gamboa,&nbsp;Estefanía Muñoz,&nbsp;José Miguel Domínguez,&nbsp;Augusto León,&nbsp;Nicolás Droppelmann,&nbsp;Antonieta Solar,&nbsp;Mark Zafereo,&nbsp;F Christopher Holsinger,&nbsp;Hernán E González","doi":"10.1007/s12672-019-0359-8","DOIUrl":"https://doi.org/10.1007/s12672-019-0359-8","url":null,"abstract":"<p><p>The use of BRAFV600E and RET/PTC1 as biomarkers to guide the extent of surgery in patients with papillary thyroid cancer (PTC) remains controversial. We assessed the combined use of demographic data (sex and age) with mRNA expression levels and/or mutational status (BRAFV600E and RET/PTC1) to identify potential subsets of patients with aggressive histopathological features (lymph node metastases and extrathyroidal extension). In a cohort of 126 consecutive patients, BRAFV600E and RET/PTC1 mutations were found in 52 and 18%, respectively. By conditional bivariate analysis (CBVA), a 'high activity' profile of BRAF (BRAFV600E positive or high expression) and 'low activity' profile of RET (RET/PTC1 negative or low expression) was associated with extrathyroidal extension (ETE) (OR 4.48). Alternatively, a 'high activity' profile of RET (RET/PTC1 positive or high expression) and 'low activity' profile of BRAF (BRAFV600E negative or low expression) were associated with lymph node metastasis (LNM) (OR 12.80). Furthermore, in patients younger than 55 years, a low expression of BRAF was associated with LNM (OR 17.65) and the presence of BRAFV600E mutation was associated with ETE (OR 2.76). Our results suggest that the analysis of demographic and molecular variables by CBVA could contribute to identify subsets of patients with aggressive histopathologic features, providing a potential guide to personalised surgical management of PTC.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"10 2-3","pages":"97-106"},"PeriodicalIF":3.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-019-0359-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9901712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aggressiveness of Localized Prostate Cancer: the Key Value of Testosterone Deficiency Evaluated by Both Total and Bioavailable Testosterone: AndroCan Study Results.","authors":"Yann Neuzillet,&nbsp;Jean-Pierre Raynaud,&nbsp;Jean-François Dreyfus,&nbsp;Camélia Radulescu,&nbsp;Mathieu Rouanne,&nbsp;Marc Schneider,&nbsp;Sylvie Krish,&nbsp;Morgan Rouprêt,&nbsp;Sarah J Drouin,&nbsp;Eva Comperat,&nbsp;Marc Galiano,&nbsp;Xavier Cathelineau,&nbsp;Pierre Validire,&nbsp;Vincent Molinié,&nbsp;Jean Fiet,&nbsp;Franck Giton,&nbsp;Thierry Lebret,&nbsp;Henry Botto","doi":"10.1007/s12672-018-0351-8","DOIUrl":"https://doi.org/10.1007/s12672-018-0351-8","url":null,"abstract":"<p><p>Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high. Improvements to patient selection and identification of at-risk patients are central to reducing mortality. We aimed to determine if cancer aggressiveness correlates with androgen levels in patients undergoing radical prostatectomy for localized PCa. We performed a prospective, multicenter cohort study between June 2013 and June 2016, involving men with localized PCa scheduled to undergo radical prostatectomy. Clinical and hormonal patient data (testosterone deficiency, defined by total testosterone (TT) levels < 300 ng/dL and/or bioavailable testosterone (BT) levels < 80 ng/dL) were prospectively collected, along with pathological assessment of preoperative biopsy and subsequent radical prostatectomy specimens, using predominant Gleason pattern (prdGP) 3/4 grading. Of 1343 patients analyzed, 912 (68%) had prdGP3 PCa and 431 (32%) had high-grade (prdGP4, i.e., ISUP ≥ 3) disease on prostatectomy specimens. Only moderate concordance in prdGP scores between prostate biopsies and prostatectomy specimens was found. Compared with patients with prdGP3 tumors (i.e., ISUP ≤ 2), significantly more patients with prdGP4 cancers had demonstrable hypogonadism, characterized either by BT levels (17.4% vs. 10.7%, p < 0.001) or TT levels (14.2% vs. 9.7%, p = 0.020). BT levels were also lower in patients with prdGP4 tumors compared to those with prdGP3 disease. Testosterone deficiency (defined by TT and/or BT levels) was independently associated with higher PCa aggressiveness. BT is a predictive factor for prdGP4 disease, and evaluating both TT and BT to define hypogonadism is valuable in preoperative assessment of PCa (AndroCan Trial: NCT02235142).</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"10 1","pages":"36-44"},"PeriodicalIF":3.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0351-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9901708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}