PCA3 in prostate cancer and tumor aggressiveness detection on 407 high-risk patients: a National Cancer Institute experience

Journal of Experimental & Clinical Cancer Research

Laura Conti¹  Michele Gallucci³  Paolo Ascenzi²  Giovanni Cigliana¹  Giuseppe Cusumano³  Manuela Costantini³  Salvatore Guaglianone³  Rocco Papalia³  Giulia Orlandi¹  Chiara Mandoj¹  Serena Masi¹  Steno Sentinelli⁴  Isabella Sperduti⁵  Anna Antenucci¹  Luigi Tomao⁶  Roberta Merola¹ 

[1] Clinical Pathology, Regina Elena National Cancer Institute, IRCCS, Via Elio Chianesi 53, Rome, 00144, Italy;Interdepartmental Laboratory of Electron Microscopy, University Roma Tre, Rome, Italy;Urology Department, Regina Elena National Cancer Institute, IRCCS, Rome, Italy;Department of Pathology, Regina Elena National Cancer Institute, IRCCS, Rome, Italy;Scientific Direction, Regina Elena National Cancer Institute, IRCCS, Rome, Italy;Department of Sciences, University Roma Tre, Rome, Italy

关键词: Tumor aggressiveness;    Prostate Cancer gene 3;    Prostate Specific Antigen;    Urine and blood biomarkers;    Prostate cancer;   

Others  :  1133386
DOI  :  10.1186/s13046-015-0127-8

 received in 2014-11-13, accepted in 2015-01-20,  发布年份 2015

【 摘 要 】

Background

Prostate cancer (PCa) is the most common male cancer in Europe and the US. The early diagnosis relies on prostate specific antigen (PSA) serum test, even if it showed clear limits. Among the new tests currently under study, one of the most promising is the prostate cancer gene 3 (PCA3), a non-coding mRNA whose level increases up to 100 times in PCa tissues when compared to normal tissues. With the present study we contribute to the validation of the clinical utility of the PCA3 test and to the evaluation of its prognostic potential.

Methods

407 Italian men, with two or more PCa risk factors and at least a previous negative biopsy, entering the Urology Unit of Regina Elena National Cancer Institute, were tested for PCA3, total PSA (tPSA) and free PSA (fPSA and f/tPSA) tests. Out of the 407 men enrolled, 195 were positive for PCa and 114 of them received an accurate staging with evaluation of the Gleason score (Gs). Then, the PCA3 score was correlated to biopsy outcome, and the diagnostic and prognostic utility were evaluated.

Results

Out of the 407 biopsies performed after the PCA3 test, 195 (48%) resulted positive for PCa; the PCA3 score was significantly higher in this population (p < 0.0001) differently to tPSA (p = 0.87). Moreover, the PCA3 test outperformed the f/tPSA (p = 0.01). The sensitivity (94.9) and specificity (60.1) of the PCA3 test showed a better balance for a threshold of 35 when compared to 20, even if the best result was achieved considering a cutoff of 51, with sensitivity and specificity of 82.1% and 79.3%, respectively. Finally, comparing values of the PCA3 test between two subgroups with increasing Gs (Gs ≤ 6 versus Gs ≥ 7) a significant association between PCA3 score and Gs was found (p = 0.02).

Conclusions

The PCA3 test showed the best diagnostic performance when compared to tPSA and f/tPSA, facilitating the selection of high-risk patients that may benefit from the execution of a saturation prostatic biopsy. Moreover, the PCA3 test showed a prognostic value, as higher PCA3 score values are associated to a greater tumor aggressiveness.

【 授权许可】

   
2015 Merola et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]Siegel R, Naishadham D, Jemal A: Cancer statistics, 2013. CA Cancer J Clin 2013, 63(1):11-30.
• [2]Barba M, Yang L, Schünemann HJ, Sperati F, Grioni S, Stranges S, et al.: Urinary estrogen metabolites and prostate cancer: a case–control study and meta-analysis. J Exp Clin Cancer Res 2009, 28:135. BioMed Central Full Text
• [3]Ribeiro R, Monteiro C, Cunha V, Oliveira MJ, Freitas M, Fraga A, et al.: Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro. J Exp Clin Cancer Res 2012, 31:32. BioMed Central Full Text
• [4]Sofra M, Antenucci A, Gallucci M, Mandoj C, Papalia R, Claroni C, et al.: Perioperative changes in pro and anticoagulant factors in prostate cancer patients undergoing laparoscopic and robotic radical prostatectomy with different anaesthetic techniques. J Exp Clin Cancer Res 2014, 33(1):63. BioMed Central Full Text
• [5]Croswell JM, Kramer BS, Crawford ED: Screening for prostate cancer with PSA testing: current status and future directions. Oncology (Williston Park) 2011, 25(6):452-60. 463
• [6]Croswell JM, Kramer BS, Crawford ED: Screening for prostate cancer with PSA testing: current status and future directions. Oncology 2011, 25(6):452-60.
• [7]Matlaga BR, Eskew LA, McCullough DL: Prostate biopsy: indications and technique. J Urol 2003, 169(1):12-9.
• [8]Raja J, Ramachandran N, Munneke G, Patel : Current status of transrectal ultrasound--guided prostate biopsy in the diagnosis of prostate cancer. Clin Radiol 2006, 61(2):142-53.
• [9]Nogueira L, Corradi R, Eastham JA: Other biomarkers for detecting prostate cancer. BJU Int 2010, 105(2):166-9.
• [10]Bussemakers MJ, van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF, Schalken JA, et al.: DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 1999, 59(23):5975-9.
• [11]Day JR, Jost M, Reynolds MA, Groskopf J, Rittenhouse H: PCA3: from basic molecular science to the clinical lab. Cancer Lett 2011, 301(1):1-6.
• [12]Luo Y, Gou X, Huang P, Mou C: The PCA3 test for guiding repeat biopsy of prostate cancer and its cut-off score: a systematic review and meta-analysis. Asian J Androl 2014, 16(3):487-92.
• [13]Andriole GL, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, Church TR, et al.: PLCO Project Team. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009, 360(13):1310-9.
• [14]Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al.: Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009, 360(13):1320-8.
• [15]Fall K, Garmo H, Andrèn O, Bill-Axelson A, Adolfsson J, Adami HO, et al.: Scandinavian Prostate Cancer Group Study No. 4. Prostate-specific antigen levels as a predictor of lethal prostate cancer. J Natl Cancer Inst 2007, 99(7):526-32.
• [16]Morote J, Rigau M, Garcia M, Mir C, Ballesteros C, Planas J, et al.: Behavior of the PCA3 gene in the urine of men with high grade prostatic intraepithelial neoplasia. World J Urol 2010, 28(6):677-80.
• [17]Auprich M, Bjartell A, Chun FK, de la Taille A, Freedland SJ, Haese A, et al.: Contemporary role of prostate cancer antigen 3 in the management of prostate cancer. Eur Urol 2011, 60(5):1045-54.
• [18]Montironi R, Mazzucchelli R, Lopez-Beltran A, Scarpelli M, Cheng L: Prostatic intraepithelial neoplasia: its morphological and molecular diagnosis and clinical significance. BJU Int 2011, 108(9):1394-401.
• [19]Hessels D, Klein Gunnewiek JMT, van Oort I, Karthaus HFM, van Leenders GJL, van Balken B, et al.: DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol 2003, 44:8-16.
• [20]Van Gils MP, Hessels D, van Hooij O, Jannink SA, Peelen WP, Hanssen SL, et al.: The time-resolved fluorescence-based PCA3 test on urinary sediments after digital rectal examination; a Dutch multicenter validation of the diagnostic performance. Clin Cancer Res 2008, 13(3):939-43.
• [21]Haese A, de la Taille A, van Poppel H, Marberger M, Stenzl A, Mulders PF, et al.: Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol 2008, 54(5):1081-8.
• [22]Bollito E, De Luca S, Cicilano M, Passera R, Grande S, Maccagnano C, et al.: Prostate cancer gene 3 urine assay cutoff in diagnosis of prostate cancer: a validation study on an Italian patient population undergoing first and repeat biopsy. Anal Quant Cytol Histol 2012, 34(2):96-104.
• [23]Filella X, Foj L, Milà M, Augé JM, Molina R, Jiménez W: PCA3 in the detection and management of early prostate cancer. Tumour Biol 2013, 34(3):1337-47.
• [24]Gittelman MC, Hertzman B, Bailen J, Williams T, Koziol I, Henderson RJ, et al.: PCA3 molecular urine test as a predictor of repeat prostate biopsy outcome in men with previous negative biopsies: a prospective multicenter clinical study. J Urol 2013, 190(1):64-9.
• [25]Goode RR, Marshall SJ, Duff M, Chevli E, Chevli KK: Use of PCA3 in detecting prostate cancer in initial and repeat prostate biopsy patients. Prostate 2013, 73:48-53.
• [26]van Poppel H, Haese A, Graefen M, de la Taille A, Irani J, de Reijke T, et al.: The relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance. BJU Int 2012, 109(3):360-6.
• [27]Heidenreich A, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V, et al.: EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol 2011, 59(1):61-71.
• [28]Albertsen PC, Moore DF, Shih W, Lin Y, Li H, Lu-Yao GL: Impact of comorbidity on survival among men with localized prostate cancer. J Clin Oncol 2011, 29(10):1335-41.
• [29]van den Bergh RC, Giannarini G: Prostate cancer: surgery versus observation for localized prostate cancer. Nat Rev Urol 2014, 11(6):312-3.
• [30]Hessels D, van Gils MP, van Hooij O, Jannink SA, Witjes JA, Verhaegh GW, et al.: Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer. Prostate 2010, 70(1):10-6.
• [31]Durand X, Xylinas E, Radulescu C, Haus-Cheymol R, Moutereau S, Ploussard G, et al.: The value of urinary prostate cancer gene 3 (PCA3) scores in predicting pathological features at radical prostatectomy. BJU Int 2012, 110(1):43-9.
• [32]Liss MA, Santos R, Osann K, Lau A, Ahlering TE, Ornstein DK: PCA3 molecular urine assay for prostate cancer: association with pathologic features and impact of collection protocols. World J Urol 2011, 29(5):683-8.
• [33]Auprich M, Chun FK, Ward JF, Pummer K, Babaian R, Augustin H, et al.: Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging. Eur Urol 2011, 59(1):96-105.
• [34]Nakanishi H, Groskopf J, Fritsche HA, Bhadkamkar V, Blase A, Kumar SV, et al.: PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. J Urol 2008, 179(5):1804-9.