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


METHODS
Retrospective pathologic study.


METHODS
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.


METHODS
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.


CONCLUSIONS
The positive correlation of MT expression with Gleason grade in prostatic adenocarcinoma suggests a possible role for MT in oncogenesis in prostate cancer.
Moussa
M
M
Department of Pathology, University of Western Ontario, London.
Kloth
D
D
Peers
G
G
Cherian
M G
MG
Frei
J V
JV
Chin
J L
JL
D014408:Biomarkers, Tumor / Q000032:analysis*; D004273:DNA, Neoplasm / Q000032:analysis*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008297:Male; D008668:Metallothionein / Q000032:analysis*; D009367:Neoplasm Staging; D011003:Ploidies; D011467:Prostate / Q000737:chemistry; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D012189:Retrospective Studies; D016196:S Phase
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D007633:Keratins; D008668:Metallothionein; D017430:Prostate-Specific Antigen