Metallothionein expression in prostatic carcinoma: correlation with Gleason grade, pathologic stage, DNA content and serum level of prostate-specific antigen

Abstract

Objective: To determine the expression of metallothionein (MT) in prostatic carcinoma by immunohistochemical staining. Several lines of evidence have indicated that MT may play a role in carcinogenesis and in drug resistance of tumours.

Design: Retrospective pathologic study.

Interventions: Formalin-fixed, paraffin-embedded archival tissues from 39 radical prostatectomies were analysed. All tumour foci were stained by ABC technique using a primary polyclonal rabbit antibody against rat liver MT. The staining intensity for MT was graded on a scale of 0 to 2+, and the histologic grading was done by the scheme of Gleason.

Outcome measures: Correlation of MT expression with Gleason grade, preoperative serum prostate-specific antigen (PSA) levels, pathologic stage and DNA content, including S-phase fraction (SPF) and proliferative index (PI).

Results: Most of the epithelium of normal prostate tissue had patchy, intense MT staining. All the grade II tumours foci showed intense (2+) staining for MT, while all grade IV and V foci were persistently negative. The grade III tumours foci were heterogeneous. The MT-positive foci showed both nuclear and cytoplasmic staining of variable extent. There were 9, 15, 13 and 2 tumours with pathologic stage B, C1, C2 and D1, respectively. The serum PSA levels ranged from 1 to 16 ng/mL. No apparent correlation existed between the MT staining pattern and the pathologic stage or preoperative PSA level. Thirty-four of the tumours were diploid and 5 were tetraploid. There were significantly higher SPF and PI mean values in the MT-stained tumour cells (p < 0.05), suggesting that MT preferentially stains an epithelial subpopulation, possibly the proliferating cell compartment.

Conclusion: The positive correlation of MT expression with Gleason grade in prostatic adenocarcinoma suggests a possible role for MT in oncogenesis in prostate cancer.