Telomerase reverse transcriptase subunit immunoreactivity: a marker for high-grade prostate carcinoma.
BACKGROUND
Telomerase, a ribonucleoprotein complex that maintains telomeric DNA, has been detected in 67-93% of prostate carcinomas by telomeric repeat-amplification protocol assay (involving polymerase chain reaction). One study used in situ hybridization in nine patients; however, to date, no immunohistochemical results have been published.


METHODS
From two hospitals, the authors compiled data on 62 patients who underwent prostatectomy from January 1996 to May 2001. Representative tissue sections were immunostained with a polyclonal antibody to telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase. Staining was evaluated by two observers and was correlated with grade, stage, and biochemical failure. There were 28 sections from low-grade to intermediate-grade tumors (Gleason score, 3-6), 14 sections with a Gleason score of 3 + 4 = 7, 9 sections with a Gleason score of 4 + 3 = 7, and 11 sections from high-grade tumors (Gleason score, 8-10).


RESULTS
From low-grade to high-grade tumors, the four groups described above disclosed nuclear reactivity in 64%, 100%, 100%, and 100% of sections, respectively. Mean percentages of 5%, 15%, 40%, and 51% of nuclei were reactive in the respective groups (P < 0.0001) with intratumoral heterogeneity. The percent of reactive tumor nuclei was not correlated with pathologic stage (P = 0.32) or margin status (P = 0.35). The basal cell layer in sections of high-grade prostatic intraepithelial neoplasia (HGPIN) and benign/atrophic acini was reactive; secretory cells were reactive in 13 of 34 HGPIN foci (38%) in 1-20% of nuclei and were never reactive in benign acini. Lymphocytes and skeletal muscle were reactive. Weak, nonspecific, cytoplasmic staining was noted in benign and tumor acini.


CONCLUSIONS
Like cytokeratin 34betaE12, nuclear anti-TERT reactivity is a basal cell marker in nonneoplastic prostatic acini. Anti-TERT reactivity is acquired by secretory cells in tumorigenesis, but consistent reactivity is restricted to high-grade carcinoma (Gleason primary pattern >or=4). This histologic evidence suggests that higher grade tumors have maximally activated telomerase and may be most responsive to antitelomerase therapy.
Iczkowski
Kenneth A
KA
Department of Pathology, University of Florida, Gainesville, Florida, USA. iczkoka@pathology.ufl.edu
Pantazis
Cooley G
CG
McGregor
Douglas H
DH
Wu
Yaping
Y
Tawfik
Ossama W
OW
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007527:Isoenzymes; D008297:Male; D009367:Neoplasm Staging; D011467:Prostate / Q000201:enzymology / Q000473:pathology; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D019098:Telomerase / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D007527:Isoenzymes; C509186:TERT protein, human; D019098:Telomerase