Androgen ablation therapy for prostate carcinoma suppresses the immunoreactive telomerase subunit hTERT.
BACKGROUND
Telomerase is a ribonucleoprotein complex that protects the ends of chromosomes from degradation. Its catalytic subunit, hTERT, controls its activity. Prior data in prostate carcinoma cases indicated that immunohistochemical hTERT reactivity increases with tumor grade and may be absent in lower grade cases. The effect of complete androgen ablation (CAA) on tumor hTERT expression was uncertain.


METHODS
hTERT immunostaining was performed on the cancerous pretreatment biopsy tissue of 30 men who consecutively underwent CAA with bicalutamide and goserelin acetate for 30 days prior to undergoing radical prostatectomy, and on their tumor tissue from radical prostatectomy. As controls, biopsy and prostatectomy samples from 30 untreated men were studied. Nuclear staining was evaluated by two observers, and the change in staining between biopsy and prostatectomy samples was evaluated using the Student t test in both groups.


RESULTS
The percent of reactive tumor nuclei in treated men declined from 36.7% to 13.2% (P = 0.0001), and declined from 19.8% to 16.1% in untreated men (P = 0.4). The greater mean hTERT reactivity in the treated men's biopsy specimens was attributed to an increased proportion of higher (Gleason score > or = 7) grade tumors. The decline in hTERT immunostaining remained significant after normalizing it to that of the untreated group (P = 0.002). The original Gleason scores, corresponding declines in the percentage of reactive tumor nuclei, and significance were: Gleason score < or = 6: 11% (P = 0.03); Gleason score of 7: 23% (P < 0.006); and Gleason score > or = 8: 46% (P < 0.005) (from a mean 63% to 17%).


CONCLUSIONS
CAA for prostate carcinoma can be considered an antitelomerase therapy. The steepest reduction in telomerase activity was noted in the highest grade tumors.
Iczkowski
Kenneth A
KA
Department of Pathology and Laboratory Medicine, University of Florida, Gainesville, FL 32608, USA. iczkoka@pathology.ufl.edu
Huang
Wei
W
Mazzucchelli
Roberta
R
Pantazis
Cooley G
CG
Stevens
Gary R
GR
Montironi
Rodolfo
R
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D020134:Catalytic Domain; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010446:Peptide Fragments / Q000378:metabolism*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D019098:Telomerase / Q000378:metabolism*; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D010446:Peptide Fragments; D014105:Tosyl Compounds; D017273:Goserelin; C053541:bicalutamide; C437311:telomerase reverse transcriptase (540-548); D019098:Telomerase