title: Are biomarkers evaluated in biopsy specimens predictive of prostate cancer aggressiveness?
abstract: OBJECTIVE
  To evaluate biomarkers involved in biological pathways for prostate cancer (PCa) progression, measured in biopsy specimens, in order to distinguish patients at higher risk for fatal PCa and thus improve the initial management of disease.
  
  
  METHODS
  Retrospective case-control study. In 129 PCa patients who underwent ultrasound-guided needle prostate biopsy and subsequent radical prostatectomy from 1987 to 1999 at the University Hospital of Careggi, we evaluated: (1) mRNA expression of the serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG); (2) expression of matrix metalloproteinases (MMP)-2 and 9 (epithelial and stromal); (3) expression of androgen receptor; (4) expression of prognostic marker Ki67 (MIB1); (5) presence and typing of human papilloma virus; (6) DNA methylation of CpG islands of several genes involved in PCa progression.
  
  
  RESULTS
  The cohort consists of 38 cases (patients with PCa and died of PCa within 10 years from diagnosis) and 91 controls (patients with PCa but alive 10 years after diagnosis). Gleason bioptic score, epithelial MMP expression and SERPINB5 methylation correlated with statistically significant increase in death risk OR. Compared with patients with high level of MMP, patients with low level of MMP had OR for specific death 4.78 times higher (p = 0.0066). After adjustment for age and Gleason score, none of the investigated biomarkers showed increased OR for PCa death.
  
  
  CONCLUSIONS
  Our preliminary results suggest that evaluation, in prostate biopsy specimens, of a panel of biomarkers known to be involved in PCa progression is poorly indicative of tumor outcome.
authors.affiliation: Laboratory Cancer Prevention, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Carozzi
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Tamburrino
authors.affiliation: Laboratory Cancer Prevention, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139, Florence, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bisanzi
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Marchiani
authors.affiliation: DAI Biomedicina SOD Istologia Patologica e Diagnostica Molecolare, AOU Careggi, Florence, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Paglierani
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Di Lollo
authors.affiliation: Clinical and Descriptive Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Florence, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Crocetti
authors.affiliation: Clinical and Descriptive Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Florence, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Buzzoni
authors.affiliation: Laboratory Cancer Prevention, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Burroni
authors.affiliation: Laboratory Cancer Prevention, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139, Florence, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Greco
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Baldi
authors.affiliation: Laboratory Cancer Prevention, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139, Florence, Italy. c.sani@ispo.toscana.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sani
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D001706:Biopsy; D016022:Case-Control Studies; D019175:DNA Methylation; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: C410798:AR protein, human; D014408:Biomarkers, Tumor; C072312:ERG protein, human; D012333:RNA, Messenger; D011944:Receptors, Androgen; C085344:SERPIN-B5; D015843:Serpins; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Biomarker; HPV; Metalloproteinase; Prostate biopsy; Prostate cancer; TMPRSS2:ERG