NY-ESO-1 expression is tightly linked to TMPRSS2-ERG fusion in prostate cancer.
BACKGROUND
NY-ESO-1 has been suggested as therapeutic cancer vaccine in prostate cancer. This study was undertaken to explore the relationship of NY-ESO-1 with tumor phenotype, biochemical recurrence, and molecular subgroups in hormone-naive prostate cancers.


METHODS
NY-ESO-1 immunohistochemistry was analyzed on a tissue microarray containing 11,152 prostate cancer samples. Results were compared to clinically follow-up data, ERG status, and deletions on PTEN, 3p13, 5q21, and 6q15.


RESULTS
NY-ESO-1 expression was absent in benign prostate glands. In prostate cancer, NY-ESO-1 positivity was found 8.8% of our 8,761 interpretable tumors including 5.8% with weak, 2.5% with moderate, and 0.5% with strong expression. There was a threefold higher rate of NY-ESO-1 expression in ERG fusion positive tumors than in ERG negative cancers (P < 0.0001). There was a significant association with early PSA recurrence, which was largely limited to ERG positive cancers. Within the ERG positive subgroup, high NY-ESO-1 expression was associated with early biochemical recurrence (P = 0.0002) and high Gleason grade (P < 0.0001). In ERG negative cancers, NY-ESO-1 expression was also linked to PTEN (P = 0.0012) and 6q15 deletions (P = 0.0005).


CONCLUSIONS
Our observations indicate a tight link of NY-ESO-1 expression to ERG activation and (to a lesser extent) PTEN- and 6q15-deletions in prostate cancer. The impact of these interactions on the likelihood of response to immunotherapy is unclear. The prognostic impact of NY-ESO-1 expression is little and not independent of histologic variables.
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.
Katharina
K
Grupp
Daniel
D
Ospina-Klinck
Maria Christina
MC
Tsourlakis
Christina
C
Koop
Waldemar
W
Wilczak
Meike
M
Adam
Ronald
R
Simon
Guido
G
Sauter
Jakob Robert
JR
Izbicki
Markus
M
Graefen
Hartwig
H
Huland
Stefan
S
Steurer
Thorsten
T
Schlomm
Sarah
S
Minner
Alexander
A
Quaas
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis*; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000032:analysis; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000032:analysis; D000071230:Transcriptional Regulator ERG
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; C072312:ERG protein, human; D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
NY-ESO-1; prostate cancer; tissue microarray