SPINK1 expression is tightly linked to 6q15- and 5q21-deleted ERG-fusion negative prostate cancers but unrelated to PSA recurrence
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SPINK1 expression is tightly linked to 6q15- and 5q21-deleted ERG-fusion negative prostate cancers but unrelated to PSA recurrence. / Grupp, Katharina; Diebel, Franz; Sirma, Hüseyin; Simon, Ronald; Breitmeyer, Karin; Steurer, Stefan; Hube-Magg, Claudia; Prien, Kristina; Pham, Taher; Weigand, Philipp; Michl, Uwe; Heinzer, Hans; Kluth, Martina; Minner, Sarah; Tsourlakis, Maria Christina; Izbicki, Jakob R; Sauter, Guido; Schlomm, Thorsten; Wilczak, Waldemar.
in: PROSTATE, Jahrgang 73, Nr. 15, 01.11.2013, S. 1690-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - SPINK1 expression is tightly linked to 6q15- and 5q21-deleted ERG-fusion negative prostate cancers but unrelated to PSA recurrence
AU - Grupp, Katharina
AU - Diebel, Franz
AU - Sirma, Hüseyin
AU - Simon, Ronald
AU - Breitmeyer, Karin
AU - Steurer, Stefan
AU - Hube-Magg, Claudia
AU - Prien, Kristina
AU - Pham, Taher
AU - Weigand, Philipp
AU - Michl, Uwe
AU - Heinzer, Hans
AU - Kluth, Martina
AU - Minner, Sarah
AU - Tsourlakis, Maria Christina
AU - Izbicki, Jakob R
AU - Sauter, Guido
AU - Schlomm, Thorsten
AU - Wilczak, Waldemar
N1 - © 2013 Wiley Periodicals, Inc.
PY - 2013/11/1
Y1 - 2013/11/1
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Carrier Proteins
KW - Chromosomes, Human, Pair 5
KW - Chromosomes, Human, Pair 6
KW - Gene Deletion
KW - Humans
KW - Male
KW - Middle Aged
KW - Neoplasm Recurrence, Local
KW - Prognosis
KW - Prostate
KW - Prostate-Specific Antigen
KW - Prostatic Neoplasms
KW - Tissue Array Analysis
KW - Trans-Activators
KW - Tumor Markers, Biological
U2 - 10.1002/pros.22707
DO - 10.1002/pros.22707
M3 - SCORING: Journal article
C2 - 23843146
VL - 73
SP - 1690
EP - 1698
JO - PROSTATE
JF - PROSTATE
SN - 0270-4137
IS - 15
ER -