title: SPINK1 Overexpression in Localized Prostate Cancer: a Rare Event Inversely Associated with ERG Expression and Exclusive of Homozygous PTEN Deletion.
abstract: SPINK1 is proposed as potential prognostic marker in prostate cancer (PCA). However, its relation to PTEN and ERG in localized PCA remains unclear. The study population consisted of two independent cohorts of men treated by radical prostatectomy for localized PCA (discovery n = 218 and validation n = 129). Patterns of association between SPINK1 and each of ERG and PTEN were evaluated by immunohistochemistry and fluorescence in situ hybridization. Associations between SPINK1 expression and various pathologic parameters and clinical outcome were also investigated. SPINK1 was expressed in 15.3 % and 10.9 % of cases in the discovery and validation cohort, respectively. SPINK expression was observed in 5.56 % of high-grade prostatic intraepithelial neoplasia and 1.1 % of adjacent morphologically benign prostatic glands. SPINK1 and ERG expression were almost exclusive, with only 1.0 % of the cases co-expressing both in the same core sample. SPINK1 interfocal and within-core heterogeneity was noted in 29.2 % and 64.6 % of cases, respectively. SPINK1 expression was not significantly associated with PTEN deletion in the two cohorts (p = 0.871 for discovery cohort and p = 0.293 for validation cohort). While SPINK1 expression did occur with hemizygous PTEN deletion, there was a complete absence of SPINK1 expression in PCA showing homozygous PTEN deletion, which was confirmed in the validation cohort (p = 0.02). Despite SPINK1's association with higher Gleason score (>7) (p = 0.02), it was not associated with other pathological parameters or biochemical recurrence post-radical prostatectomy. We documented absolute exclusivity between SPINK1 overexpression and homozygous PTEN deletion in localized PCA. SPINK1 and ERG expressions are exclusive events in PCA. SPINK1 is not of added prognostic value in localized PCA.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, 7007, 14sth st sw, Calgary, AB, T2V 1P9, Canada.
authors.forename: Kuo-Cheng
authors.initials: KC
authors.lastname: Huang
authors.affiliation: Department of Pathology, Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, ON, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Evans
authors.affiliation: Department of Urology, University of Calgary, Calgary, AB, Canada.|The Prostate Cancer Center, Calgary, AB, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: Donnelly
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, 7007, 14sth st sw, Calgary, AB, T2V 1P9, Canada. tarek.bismar@cls.ab.ca.|Departments of Oncology, Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada. tarek.bismar@cls.ab.ca.|Southern Alberta Cancer Institute and Tom Baker Cancer Center, Calgary, AB, Canada. tarek.bismar@cls.ab.ca.|The Prostate Cancer Center, Calgary, AB, Canada. tarek.bismar@cls.ab.ca.
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Bismar
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008297:Male; D060787:Neoplasm Grading / Q000379:methods; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011379:Prognosis; D011467:Prostate / Q000473:pathology; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D000071230:Transcriptional Regulator ERG / Q000235:genetics; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C072312:ERG protein, human; C486642:SPINK1 protein, human; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Biomarkers; ERG; Hemizygous; Homozygous; PTEN deletion; Progression; Prostate cancer; SPINK1