title: Saccharomyces cerevisiae-like 1 overexpression is frequent in prostate cancer and has markedly different effects in Ets-related gene fusion-positive and fusion-negative cancers.
abstract: The cytosolic factor Saccharomyces cerevisiae-like 1 (SEC14L1) is a regulator of lipid metabolism and signaling pathways that has been suggested to play a role in cancer. To learn more about its relevance for prostate cancer, SEC14L1 expression was analyzed on a tissue microarray containing samples from 11152 prostate cancer patients. In benign prostate glands, SEC14L1 immunostaining was absent or weak. In prostate cancer, SEC14L1 positivity was found in 80% of 9876 interpretable tumors including 9% with strong, 38% with moderate, and 32% with weak immunostaining. SEC14L1 expression was more frequent in Transmembrane Protease, Serine 2 (TMPRSS2):Ets-related gene (ERG) fusion-positive (89%) than in TMPSSR2:ERG-negative cancers (73%, P < .0001). Comparative analysis of SEC14L1 expression in TMPSSR2:ERG-positive and -negative cancers suggested a different role of SEC14L1 in the 2 subsets: in TMPSSR2:ERG-negative cancers, strong SEC14L1 expression was associated with early prostate-specific antigen recurrence (P = .0270), advanced tumor stage (P = .0042), high Gleason score (P < .0001), and high preoperative prostate-specific antigen levels (P = .0035). In TMPSSR2:ERG-positive cancers, strong SEC14L1 staining was linked to a prolonged recurrence-free interval (P = .0023) and absence of lymph node metastases (P = .0002). Strong associations of high SEC14L1 levels with chromosomal deletions (5q, 6q, phosphatase and tensin homolog gene, 3p13; P < .0001) and a high Ki-67 labeling index (P < .0001) were seen in TMPSSR2:ERG-negative but not TMPSSR2:ERG-positive cancers. A direct or indirect role of SEC14L1 in maintenance of genomic integrity and regulating cell proliferation may thus exclusively exist in TMPSSR2:ERG-negative cancers. In conclusion, our data suggest a markedly different role of SEC14L1 in TMPSSR2:ERG-negative and TMPSSR2:ERG-positive prostate cancers.
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246; General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Christoph
authors.initials: C
authors.lastname: Burdelski
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Ysé
authors.initials: Y
authors.lastname: Barreau
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hube-Magg
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Christina
authors.initials: C
authors.lastname: Koop
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Hans
authors.initials: H
authors.lastname: Heinzer
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Corinna
authors.initials: C
authors.lastname: Wittmer
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Meike
authors.initials: M
authors.lastname: Adam
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246; Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246.
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Tsourlakis
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 20246. Electronic address: aquaas@uke.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Quaas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis / Q000379:methods; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D015514:Oncogene Proteins, Fusion; C100642:SEC14L1 protein, human; C515553:TMPRSS2-ERG fusion protein, human; D017430:Prostate-Specific Antigen
keywords: Prognosis; Prostate cancer; SEC14L1; TMPSSR2:ERG; Tissue microarray