title: PCA3 in prostate cancer and tumor aggressiveness detection on 407 high-risk patients: a National Cancer Institute experience.
abstract: 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.
authors: Clinical Pathology, Regina Elena National Cancer Institute, IRCCS, Via Elio Chianesi 53, 00144, Rome, Italy. merola@ifo.it.
authors: Roberta
authors: R
authors: Merola
authors: Clinical Pathology, Regina Elena National Cancer Institute, IRCCS, Via Elio Chianesi 53, 00144, Rome, Italy. ltomao@uniroma3.it.|Department of Sciences, University Roma Tre, Rome, Italy. ltomao@uniroma3.it.
authors: Luigi
authors: L
authors: Tomao
authors: Clinical Pathology, Regina Elena National Cancer Institute, IRCCS, Via Elio Chianesi 53, 00144, Rome, Italy. antenucci@ifo.it.
authors: Anna
authors: A
authors: Antenucci
authors: Scientific Direction, Regina Elena National Cancer Institute, IRCCS, Rome, Italy. sperduti@ifo.it.
authors: Isabella
authors: I
authors: Sperduti
authors: Department of Pathology, Regina Elena National Cancer Institute, IRCCS, Rome, Italy. sentinelli@ifo.it.
authors: Steno
authors: S
authors: Sentinelli
authors: Clinical Pathology, Regina Elena National Cancer Institute, IRCCS, Via Elio Chianesi 53, 00144, Rome, Italy. masi@ifo.it.
authors: Serena
authors: S
authors: Masi
authors: Clinical Pathology, Regina Elena National Cancer Institute, IRCCS, Via Elio Chianesi 53, 00144, Rome, Italy. chiaramandoj@yahoo.it.
authors: Chiara
authors: C
authors: Mandoj
authors: Clinical Pathology, Regina Elena National Cancer Institute, IRCCS, Via Elio Chianesi 53, 00144, Rome, Italy. g.orlandi2007@yahoo.it.
authors: Giulia
authors: G
authors: Orlandi
authors: Urology Department, Regina Elena National Cancer Institute, IRCCS, Rome, Italy. mpurri@yahoo.it.
authors: Rocco
authors: R
authors: Papalia
authors: Urology Department, Regina Elena National Cancer Institute, IRCCS, Rome, Italy. urologiaroma@virgilio.it.
authors: Salvatore
authors: S
authors: Guaglianone
authors: Urology Department, Regina Elena National Cancer Institute, IRCCS, Rome, Italy. m.costantini@unicampus.it.
authors: Manuela
authors: M
authors: Costantini
authors: Urology Department, Regina Elena National Cancer Institute, IRCCS, Rome, Italy. cusumano@ifo.it.
authors: Giuseppe
authors: G
authors: Cusumano
authors: Clinical Pathology, Regina Elena National Cancer Institute, IRCCS, Via Elio Chianesi 53, 00144, Rome, Italy. cigliana@ifo.it.
authors: Giovanni
authors: G
authors: Cigliana
authors: Department of Sciences, University Roma Tre, Rome, Italy. ascenzi@uniroma3.it.|Interdepartmental Laboratory of Electron Microscopy, University Roma Tre, Rome, Italy. ascenzi@uniroma3.it.
authors: Paolo
authors: P
authors: Ascenzi
authors: Urology Department, Regina Elena National Cancer Institute, IRCCS, Rome, Italy. gallucci@ifo.it.
authors: Michele
authors: M
authors: Gallucci
authors: Clinical Pathology, Regina Elena National Cancer Institute, IRCCS, Via Elio Chianesi 53, 00144, Rome, Italy. laura.conti@ifo.it.
authors: Laura
authors: L
authors: Conti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C479341:prostate cancer antigen 3, human; D017430:Prostate-Specific Antigen
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