Expression of the androgen-regulated fusion gene TMPRSS2-ERG does not predict response to endocrine treatment in hormone-naïve, node-positive prostate cancer.
BACKGROUND
Fusion of the androgen-regulated gene transmembrane protease, serine 2, TMPRSS2, to the v-ets erythroblastosis virus E26 oncogene homolog (avian), ERG, of the erythroblast transformation-specific (ETS) family is the most common genetic alteration in prostate cancer (PCa).


OBJECTIVE
To determine whether expression of androgen-regulated TMPRSS2-ERG predicts response to endocrine treatment in hormone-naïve, node-positive PCa.


METHODS
Eighty-five patients with histologically confirmed, node-positive PCa who were without treatment at the moment of lymph node dissection were analysed. RNA was isolated from the paraffin-embedded lymph node metastases and complementary DNA (cDNA) was made. The quality of cDNA was tested by polymerase chain reaction (PCR) analysis of the expression of the housekeeping gene hydroxymethylbilane synthase, HMBS (formerly PBGD). TMPRSS2-ERG expression was analysed by PCR using a forward primer in TMPRSS2 exon 1 and a reverse primer in ERG exon 4.


METHODS
The primary end point was time from start of endocrine therapy to the occurrence of three consecutive rises in prostate-specific antigen (PSA) that were at least 2 wk apart and resulted in two 50% increases over the PSA nadir. Secondary end points were time to PSA nadir after start of endocrine treatment and cancer-specific and overall survival.


CONCLUSIONS
TMPRSS2-ERG was expressed in 59% of the 71 patients who could be analysed. Median duration of response to endocrine therapy was 20.9 mo versus 24.1 mo for gene fusion-positive versus gene fusion-negative patients (95% confidence intervals: 18.6-23.1 vs 18.9-29.4, p=0.70). Furthermore, no significant differences were seen between the two groups for the secondary end points.


CONCLUSIONS
Expression of TMPRSS2-ERG is frequent in lymph node metastases of patients with untreated PCa; however, expression of this androgen-regulated fusion gene did not correspond with duration of response to endocrine therapy. Our results suggest that expression of TMPRSS2-ERG is not a candidate marker to select for metastatic PCa patients who will benefit more from endocrine treatment.
Boormans
Joost L
JL
Department of Urology, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands.
Hermans
Karin G
KG
Made
Angelique C J Ziel-van der
AC
van Leenders
Geert J H L
GJ
Wildhagen
Mark F
MF
Collette
Laurence
L
Schröder
Fritz H
FH
Trapman
Jan
J
Verhagen
Paul C M S
PC
D000726:Androgen Antagonists / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis* / Q000235:genetics; D009919:Orchiectomy; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*
D000726:Androgen Antagonists; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D007987:Gonadotropin-Releasing Hormone