A POTENTIAL AUTOCRINE LOOP BETWEEN HEREGULIN-ALPHA AND ERBB-3 RECEPTOR IN HUMAN PROSTATIC ADENOCARCINOMA

Objective To examine the expression of heregulin-alpha (a new member o f the epidermal growth factor family) and its receptor erbB-3 in human prostate cancer by immunohistochemistry, and to analyse their implica tion for clinical outcome. Patients and method Using specific anti-pep tide antibodies, tumour samples from 50 consecutive patients with newl y diagnosed prostate cancer (18 well, 15 moderately and 17 poorly diff erentiated) and four patients with benign prostatic hyperplasia (BPH) were immunostained for heregulin-alpha (an isoform of heregulin) and e rbB-3 proteins. Representative areas from each case were used to asses s immunoreactivity. Results Heregulin-alpha was expressed (i.e. greate r than or equal to 10% of tumour cells positive) in 36 (72%) and erbB- 3 in 27 (54%) of the 50 cases, High levels of expression of heregulin- alpha (> 90% of tumour cells stained) appeared to be related to high-g rade rumours, but the association did not reach statistical significan ce. There was no correlation between the levels of expression of erbB- 3 and tumour grade, All four samples from BPH stained negatively for h eregulin-alpha and erbB-3. Fourteen patients had bony metastases ident ified by bone scintigraphy and all received androgen ablation after un dergoing transurethral resection of the prostate, Immunoreactivity for heregulin-alpha and erbB-3 were absent in Eve cases, all of whom resp onded to hormone manipulation and remained symptom-free at the time of review (mean follow up 3 years, range 2-4), Despite hormone manipulat ion, the nine patients overexpressing heregulin-alpha and/or erbB-3 di ed during a mean follow up of 2.5 years (range 0.5-4).Conclusion The o verexpression of heregulin-alpha and erbB-3 in prostate cancer is dete ctable by immunostaining, Activation of the type 1 growth-factor recep tor system by heregulin-alpha and/or the erbB-3 receptor appears to be associated with a less favourable prognosis in advanced disease.