Biomedical subjects

Cooley G Pantazis

Publications and source records attributed to Cooley G Pantazis.

5 recordsLinked to original sources

PubMed2004

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.

Aged↗

PubMed2003

Overexpression of NSAID-activated gene product in prostate cancer.

NSAID-activated gene (NAG-1) protein was previously identified by microarray analysis as overexpressed in prostate cancer. We performed immunohistochemistry and Western blotting with rabbit polyclonal antibody to NAG-1. Fifty malignant tissues obtained by prostatectomy and 17 from benign cases were compiled. Cancer tissues included Gleason scores 3-6, 3+4=7, 4+3=7, and 8-10. Cancer and high-grade prostatic intraepithelial neoplasia (PIN) consistently showed moderate to intense cytoplasmic reactivity in 95-100% of epithelium. Staining intensity inversely correlated with preoperative serum prostate-specific antigen (PSA) (p=0.005) and with grade, averaging (on a 0 to 3+ scale) 2.3 +/- 0.6 in the lowest grade group, and 2.0 +/- 0.7, 1.8 +/- 0.5, and 1.5 +/- 0.6 as grade increased (p<0.008). Benign epithelium was nonreactive in 17/17 specimens without concurrent cancer (11 transurethral resection, 2 enucleation, 4 biopsy, p=0.002). Decreased NAG-1 expression in higher grade cancer is consistent with its known antitumorigenic, proapoptotic activities.

Biomarkers, Tumor↗

PubMed2002

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.

Adenocarcinoma↗

PubMedDate not supplied

Lobular carcinoma of the breast metastatic to the epidural space: a potential mimic of giant cell bone tumor.

We report the case of a 64-year-old woman with a spinal epidural mass. Tissue from a decompression laminectomy disclosed a tumor with numerous osteoclast-like giant cells separated by small, moderately atypical tumor cells. The osteoclast-like giant cells were immunoreactive for vimentin, but negative for epithelial membrane antigen and broad-pectrum cytokeratin. Subsequent breast biopsy revealed a lobular carcinoma of classic type without osteoclast-like giant cells. This is the first reported case in which metastatic breast carcinoma was accompanied by these giant cells but the giant cells were not present at the primary tumor site.

Breast Neoplasms↗

PubMedDate not supplied

Prostate cancer overexpresses CD44 variants 7-9 at the messenger RNA and protein level.

BACKGROUND: In prostate cancer, prior data show down-regulated immunohistochemical expression of cell adhesion protein CD44 standard (CD44s) and most variants (CD44v). MATERIALS AND METHODS: Expression of CD44 mRNA was studied by RT-PCR and cDNA sequencing in 19 prostate cancers and 10 benign controls. Immunohistochemical staining was performed with anti-CD44v7/8 in 80 prostatectomy specimens, and 12 were used for in situ hybridization for CD44v7 (exon 12). Western blotting with monoclonal antibody to CD44 standard, v6, v7/8, or v9 was performed using cancerous and benign prostate. RESULTS: Sequencing of RT-PCR products showed that benign tissue and cancer express CD44 standard and v10 mRNA at 482 base pairs (bp). In contrast, cancer tissues also overexpressed 800-1000 bp bands corresponding to v7-9 isoforms. In situ hybridization revealed increased CD44v7 signal in cancer compared to benign acini. Immunostaining for CD44v7/8 was increased, proportional to Gleason grade. By Western blot, cancer and benign tissue disclosed major bands of reactivity at 75-100 kD consistent with intact standard and variant isoforms. Tumors, however, had 6-45 kD bands for CD44 standard, v7/8 and v9, consistent with cleavage products. CONCLUSION: CD44 v7-9 isoform messenger RNA is increased in prostate cancer, and translation yields low molecular weight polypeptides of probable cleavage origin.

Blotting, Western↗