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
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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. / Burdelski, Christoph; Barreau, Ysé; Simon, Ronald; Hube-Magg, Claudia; Minner, Sarah; Koop, Christina; Graefen, Markus; Heinzer, Hans; Sauter, Guido; Wittmer, Corinna; Steurer, Stefan; Adam, Meike; Huland, Hartwig; Schlomm, Thorsten; Tsourlakis, Maria Christina; Quaas, Alexander.
In: HUM PATHOL, Vol. 46, No. 4, 01.04.2015, p. 514-23.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - 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
AU - Burdelski, Christoph
AU - Barreau, Ysé
AU - Simon, Ronald
AU - Hube-Magg, Claudia
AU - Minner, Sarah
AU - Koop, Christina
AU - Graefen, Markus
AU - Heinzer, Hans
AU - Sauter, Guido
AU - Wittmer, Corinna
AU - Steurer, Stefan
AU - Adam, Meike
AU - Huland, Hartwig
AU - Schlomm, Thorsten
AU - Tsourlakis, Maria Christina
AU - Quaas, Alexander
N1 - Copyright © 2015 Elsevier Inc. All rights reserved.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.humpath.2014.06.006
DO - 10.1016/j.humpath.2014.06.006
M3 - SCORING: Journal article
C2 - 25701228
VL - 46
SP - 514
EP - 523
JO - HUM PATHOL
JF - HUM PATHOL
SN - 0046-8177
IS - 4
ER -