Metallothionein isoform II expression in hyperplastic, dysplastic and neoplastic prostatic lesions

Abstract

Background: Metallothionein is a low-molecular-weight cysteine-rich protein that has the ability to bind and sequestrate heavy metal ions. It is associated with metalloregulatory functions such as cell proliferation, growth and differentiation.

Aims: To investigate the expression of metallothionein in hyperplastic, dysplastic and neoplastic prostatic lesions and to correlate its expression with histological grade of prostatic carcinoma.

Method: The study was carried out on formalin-fixed and paraffin-wax-embedded tissue blocks from 8 patients with benign prostatic hyperplasia, 6 patients with prostatic intraepithelial neoplasia (PIN) and 30 patients with prostatic carcinoma, using the streptavidin–biotin technique. The histological grade was defined and the carcinomas were divided into low-grade (Gleason Score 2–4), 12 moderate grade (Gleason Score 5–6) and 10 high-grade (Gleason Score 7–10) carcinomas.

Results: Patchy metallothionein staining of epithelial cells was observed in normal and benign prostatic tissues. All cases of PIN and 20 of 30 patients with prostatic carcinoma showed positive staining for metallothionein. Metallothionein expression considerably increased from low-grade to high-grade tumours. The proportion of cells staining positively for metallothionein was directly correlated with histological grade of prostatic carcinoma. The epithelial cells lack uniformity in staining intensity, but the percentage of strongly positive cells increased with the histological grade of prostatic carcinoma.

Conclusions: The high incidence of metallothionein expression in PIN in our study suggests that it is associated with early prostate tumorigenesis. Also, metallothionein expression was directly correlated with the histological grade of prostatic carcinoma, suggesting that metallothionein may be a useful marker for predicting the prognosis of prostate cancer.