title: SPINK1 protein expression and prostate cancer progression.
abstract: OBJECTIVE
  SPINK1 overexpression has been described in prostate cancer and is linked with poor prognosis in many cancers. The objective of this study was to characterize the association between SPINK1 overexpression and prostate cancer-specific survival.
  
  
  METHODS
  The study included 879 participants in the U.S. Physicians' Health Study and Health Professionals Follow-Up Study, diagnosed with prostate cancer (1983-2004) and treated by radical prostatectomy. Protein tumor expression of SPINK1 was evaluated by immunohistochemistry on tumor tissue microarrays.
  
  
  RESULTS
  Seventy-four of 879 (8%) prostate cancer tumors were SPINK1 positive. Immunohistochemical data were available for PTEN, p-Akt, pS6, stathmin, androgen receptor (AR), and ERG (as a measure of the TMPRSS2:ERG translocation). Compared with SPINK1-negative tumors, SPINK1-positive tumors showed higher PTEN and stathmin expression, and lower expression of AR (P < 0.01). SPINK1 overexpression was seen in 47 of 427 (11%) ERG-negative samples and in 19 of 427 (4%) ERG-positive cases (P = 0.0003). We found no significant associations between SPINK1 status and Gleason grade or tumor stage. There was no association between SPINK1 expression and biochemical recurrence (P = 0.56). Moreover, there was no association between SPINK1 expression and prostate cancer mortality (there were 75 lethal cases of prostate cancer during a mean of 13.5 years follow-up; HR = 0.71; 95% confidence interval, 0.29-1.76).
  
  
  CONCLUSIONS
  Our results suggest that SPINK1 protein expression may not be a predictor of recurrence or lethal prostate cancer amongst men treated by radical prostatectomy. SPINK1 and ERG protein expression do not seem to be entirely mutually exclusive, as some previous studies have suggested.
authors.affiliation: Center for Molecular Oncologic Pathology; Departments of Department of Histopathology, St. James's Hospital and Trinity College Dublin Medical School, Dublin, Ireland rflavin@stjames.ie.
authors.forename: Richard
authors.initials: R
authors.lastname: Flavin
authors.affiliation: Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pettersson
authors.affiliation: Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
authors.forename: Whitney K
authors.initials: WK
authors.lastname: Hendrickson
authors.affiliation: Center for Molecular Oncologic Pathology; Departments of.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.affiliation: Center for Molecular Oncologic Pathology; Departments of Department of Histopathology, St. James's Hospital and Trinity College Dublin Medical School, Dublin, Ireland.
authors.forename: Stephen
authors.initials: S
authors.lastname: Finn
authors.affiliation: Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
authors.forename: Lauren
authors.initials: L
authors.lastname: Kunz
authors.affiliation: Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Judson
authors.affiliation: Center for Molecular Oncologic Pathology; Departments of.
authors.forename: Rosina
authors.initials: R
authors.lastname: Lis
authors.affiliation: Center for Molecular Oncologic Pathology; Departments of.
authors.forename: Dyane
authors.initials: D
authors.lastname: Bailey
authors.affiliation: Center for Molecular Oncologic Pathology; Departments of.
authors.forename: Christopher
authors.initials: C
authors.lastname: Fiore
authors.affiliation: Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nuttall
authors.affiliation: Radiation Oncology, Dana Farber Cancer Institute;
authors.forename: Neil E
authors.initials: NE
authors.lastname: Martin
authors.affiliation: Center for Molecular Oncologic Pathology; Departments of.
authors.forename: Edward
authors.initials: E
authors.lastname: Stack
authors.affiliation: Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Penney
authors.affiliation: Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Rider
authors.affiliation: Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sinnott
authors.affiliation: Medical Oncology and.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sweeney
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital;
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
authors.affiliation: Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
authors.forename: Katja
authors.initials: K
authors.lastname: Fall
authors.affiliation: Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.affiliation: Medical Oncology and.
authors.forename: Philip
authors.initials: P
authors.lastname: Kantoff
authors.affiliation: Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
authors.forename: Meir
authors.initials: M
authors.lastname: Stampfer
authors.affiliation: Center for Molecular Oncologic Pathology; Departments of Medical Oncology and.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.affiliation: Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002352:Carrier Proteins / Q000096:biosynthesis*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic