title: SPINK1 expression is tightly linked to 6q15- and 5q21-deleted ERG-fusion negative prostate cancers but unrelated to PSA recurrence.
abstract: BACKGROUND
  The serine peptidase inhibitor, Kazal type 1 (SPINK1) has been suggested to define an aggressive molecular subtype of ERG-fusion negative prostate cancer. It was the aim of this study to further study the clinical relevance of SPINK1 expression and its relationship with other key genomic alterations of prostate cancer.
  
  
  METHODS
  A tissue microarray containing more than 10,000 prostate cancers with clinical follow-up was used for immunohistochemical SPINK1 analysis. Data on ERG status as well as PTEN, 6q, 5q, and 3p deletions were available for comparison.
  
  
  RESULTS
  SPINK1 expression was absent in benign prostate glands and detectable in 5.9% of 9,503 interpretable prostate cancers. Presence of SPINK1 expression was markedly more frequent in ERG negative (10.4%) than in ERG positive cancers (0.3%; P < 0.0001). However, SPINK1 expression was unrelated to tumor phenotype and biochemical recurrence in all cancers and in the subgroup of ERG negative cancers. Further subgroup analyses revealed, however, that--within ERG negative cancers--SPINK1 expression was significantly linked to deletions at 6q15 (P < 0.0001) and 5q21 (P = 0.0042).
  
  
  CONCLUSIONS
  Our results exclude SPINK1 as a relevant prognostic prostate cancer biomarker. However, the data demonstrate that SPINK1 overexpression is tightly linked to the small subsets of 6q15- and 5q21-deleted ERG negative prostate cancers. These findings support the concept of molecularly defined subtypes of prostate cancers.
authors.affiliation: General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Grupp
authors.forename: Franz
authors.initials: F
authors.lastname: Diebel
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Sirma
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Karin
authors.initials: K
authors.lastname: Breitmeyer
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
authors.forename: Claudia
authors.initials: C
authors.lastname: Hube-Magg
authors.forename: Kristina
authors.initials: K
authors.lastname: Prien
authors.forename: Taher
authors.initials: T
authors.lastname: Pham
authors.forename: Philipp
authors.initials: P
authors.lastname: Weigand
authors.forename: Uwe
authors.initials: U
authors.lastname: Michl
authors.forename: Hans
authors.initials: H
authors.lastname: Heinzer
authors.forename: Martina
authors.initials: M
authors.lastname: Kluth
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Tsourlakis
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002895:Chromosomes, Human, Pair 5; D002896:Chromosomes, Human, Pair 6; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C072312:ERG protein, human; C486642:SPINK1 protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic; D017430:Prostate-Specific Antigen
keywords: SPINK1; prostate cancer; tissue microarray