Elevated levels of HER-2/neu and androgen receptor in clinically localized prostate cancer identifies metastatic potential.
BACKGROUND
In this study, we investigated the expression of HER-2/neu and AR in clinically organ-confined prostate cancer to determine whether alterations in these signaling pathways contribute to the development of metastatic disease.


METHODS
HER-2/neu and AR immunoreactivity were evaluated in archived prostatic tissues obtained from 53 men with clinically organ-confined disease who underwent radical prostatectomy. Associations between AR and HER-2/neu immunostaining and disease outcome were determined.


RESULTS
Seventy percent (37/53) of tumors exhibited high levels of HER-2/neu immunostaining and 68% (36/53) of tumors had elevated AR levels. Patients with high levels of both HER-2/neu and AR had the highest rate of PSA failure (56%, 15/27) compared with no PSA failures amongst seven patients with low levels of both HER-2/neu and AR (log rank statistic 7.69, P = 0.021). Concurrent high levels of HER-2/neu and AR expression were significantly associated with high pathological stage (P = 0.027) and development of metastatic disease (P = 0.022).


CONCLUSIONS
These findings support the notion that both the HER-2/neu and AR signaling pathways may contribute to development of metastatic disease. The subset of prostate tumors with increased HER-2/neu and AR levels may benefit from treatment strategies that target both signaling pathways.
Ricciardelli
Carmela
C
Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, Australia. carmela.ricciardelli@adelaide.edu.au
Jackson
Michael W
MW
Choong
Catherine S
CS
Stahl
Jürgen
J
Marshall
Villis R
VR
Horsfall
David J
DJ
Tilley
Wayne D
WD
D000368:Aged; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000276:immunology; D011944:Receptors, Androgen / Q000032:analysis* / Q000276:immunology
D017430:Prostate-Specific Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; C508053:ERBB2 protein, human