A potential autocrine loop between heregulin-alpha and erbB-3 receptor in human prostatic adenocarcinoma

To examine the expression of heregulin-alpha (a new member of the epidermal growth factor family) and its receptor erbB-3 in human prostate cancer by immunohistochemistry, and to analyse their implication for clinical outcome.

Using specific anti-peptide antibodies, tumour samples from 50 consecutive patients with newly diagnosed prostate cancer (18 well, 15 moderately and 17 poorly differentiated) and four patients with benign prostatic hyperplasia (BPH) were immunostained for heregulin-alpha (an isoform of heregulin) and erbB-3 proteins. Representative areas from each case were used to assess immunoreactivity.

Heregulin-alpha was expressed (i.e. > or = 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-grade tumours, but the association did not reach statistical significance. There was no correlation between the levels of expression of erbB-3 and tumour grade. All four samples from BPH stained negatively for heregulin-alpha and erbB-3. Fourteen patients had bony metastases identified by bone scintigraphy and all received androgen ablation after undergoing transurethral resection of the prostate. Immunoreactivity for heregulin-alpha and erbB-3 were absent in five cases, all of whom responded to hormone manipulation and remained symptom-free at the time of review (mean follow up 3 years, range 2-4). Despite hormone manipulation, the nine patients overexpressing heregulin-alpha and/or erbB-3 died during a mean follow up of 2.5 years (range 0.5-4).

The overexpression of heregulin-alpha and erbB-3 in prostate cancer is detectable by immunostaining. Activation of the type 1 growth-factor receptor system by heregulin-alpha and/or the erbB-3 receptor appears to be associated with a less favourable prognosis in advanced disease.