Detection of telomerase activity in prostate massage samples improves differentiating prostate cancer from benign prostatic hyperplasia

Vicentini, Carlo; Gravina, Giovanni Luca; Angelucci, Adriano; Pascale, Esterina; D’Ambrosio, Ettoré; Muzi, Paola; Leonardo, Gabriella Di; Fileni, Antonio; Tubaro, Andrea; Festuccia, Claudio; Bologna, Mauro

doi:10.1007/s00432-003-0525-8

Cited by 23 publications

(22 citation statements)

References 21 publications

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“…Because tumor cells may be present in low numbers and because the enzymatic activity of telomerase and the PCR efficiency might be affected by the presence of inhibitors in urine, we combined the standardized sample processing with highly sensitive measurements of telomerase activity by quantitative real-time PCR. In contrast to previously published studies (35,41,42) that have reported telomerase activity in exfoliated cells in prostatic fluid and urine in 90%, 91%, and 58% of prostate cancer patients, respectively, in the present study, all patients with clinically localized prostate cancer have shown relatively high levels of telomerase activity that corresponds to 100% of the assay sensitivity. These data are in agreement with basic knowledge that tumor cells exfoliate early during carcinogenesis, before the primary tumor can be detected by standard clinical tests (CAP Today Archive, July 1998).…”

Section: Discussioncontrasting

confidence: 99%

“…Our study had principal differences with similar recently published studies (35,41,42). First, we collected post-prostatic massage exfoliated cells prospectively, without prior knowledge of clinicopathologic data.…”

Section: Discussionmentioning

confidence: 99%

“…One of the most promising candidates for this role is telomerase. However, only limited data exist about the correlation of telomerase activity in exfoliated cells in urine with prostate clinicopathology (35,41,42). In addition, accurate quantitative methods of telomerase activity measurements are required for reliable evaluation of the clinical utility of telomerase.…”

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confidence: 99%

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Noninvasive Detection of Prostate Cancer by Quantitative Analysis of Telomerase Activity

Botchkina¹,

Kim²,

Botchkina³

et al. 2005

Clinical Cancer Research

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Purpose: Prostate cancer is the most common male malignancy and the second leading cause of male cancer death; therefore, there is urgent necessity for noninvasive assays for early detection of prostate cancer. Obtaining prostate tumor samples surgically is problematic because the malignancy is heterogeneous and multifocal and early-stage tumors are nonpalpable. In contrast, exfoliated cells represent the cancer status of the entire gland better due to the general tendency of cancer cells to exfoliate into biological fluids. The purpose of this study was to clarify whether quantitative analysis of telomerase activity in exfoliated cells in urine could serve as a reliable molecular marker of prostate malignancy. Experimental Design: We analyzed prospectively post-prostatic examination^exfoliated cells from the urine of 56 patients undergoing routine prostate screening. Epithelial cells were isolated and enriched by immunomagnetic separation. Telomerase activity was analyzed by quantitative real-time PCR telomeric-repeat amplification protocol assay using Opticon MJ research instrument. Results: We report now that all prostate cancer patients revealed high levels of telomerase activity thereby showing 100% of the assay sensitivity. In contrast, the majority of patients with clinically confirmed benign prostatic hyperplasia (BPH) did not express any telomerase activity (70% of all BPH patients), most likely presenting cancer-free cases, or expressed low levels of activity (18%). However, about 12% of BPH patients revealed high levels of telomerase activity that potentially can reflect hidden prostate cancer. Conclusions: We suggest that the quantitative analysis of telomerase activity can be useful for the selection of prostate cancer and cancer-free cases.Prostate cancer is the most common male malignancy and the second leading cause of male cancer-related death (1, 2). Small prostatic carcinomas were detected in 30% of men ages 30 to 49 years, 40% of males over age 50, and 64% of men ages 60 to 70 years (3 -5). For this reason, an annual screening is generally recommended for all men over the age of 50.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Noninvasive Detection of Prostate Cancer by Quantitative Analysis of Telomerase Activity

Botchkina¹,

Kim²,

Botchkina³

et al. 2005

Clinical Cancer Research

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“…Tissue samples were cultured in DMEM as previously described (31)(32)(33). Cultured cells were analysed for the presence of AR, EGFR, prostate-specific antigen (PSA) and telomerase activity, TRAP (34).…”

Section: Methodsmentioning

confidence: 99%

Gefitinib and bicalutamide show synergistic effects in primary cultures of prostate cancer derived from androgen-dependent naive patients

Festuccia

Gravina²,

Muzi³

et al. 2007

Oncol Rep

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Abstract. We previously demonstrated that the inhibition of the epidermal growth factor receptor (EGFR) signalling affects the endocrine therapy responses of prostate cancer (PCa) cells and that bicalutamide (BCLT) is able to reinforce PI3K activity through mechanisms involving PTEN decrement and EGFR and Her2 activities. The aim of this study was to evaluate if the hormonal therapy with BCLT can affect the EGFR-targeted therapy using primary cultures obtained from 22 human PCa tissues harvested after radical prostatectomy (RP) in patients who received (n=10) BCLT and those that did not (n=12) as neoadjuvant hormone therapy (NHT). We demonstrated that cultures derived from PCa tissues harvested after NHT presented significantly higher EGFR and Her2 levels compared to cultures derived from control patients. However, cultures derived from patients with NHT were less sensitive to gefitinib when compared to cultures derived from control patients. Conversely, BCLT effectiveness did not seem to be different in the two groups and was partially additive with gefitinib in the NHT group and additive/synergistic in the control group. Cultures (8/22) were negative for the expression of the PTEN gene and we observed no differences in the two groups. Thus the different IC 50 values observed for gefitinib and the partial additivity in the combination treatment with gefitinib and BCLT is influenced by EGFR/Her2 ratio because it was shown that EGFR inhibition was lower when Her2 is overexpressed. Taken together, our results indicate that anti-EGFR targeted therapies and a possible combination therapy involving gefitinib and BCLT should be performed early in naive patients when Her2 is not overexpressed and before the antiandrogenic hormone therapy induces such an undesirable effect.

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“…Several groups have measured telomerase activity with the telomeric repeat amplification protocol assay and obtained sensitivities of 58, 90 and 100% and specificities of 100, 87 and 89%, respectively. [25][26][27] Meid et al 25 also found a significant association between Gleason score and telomerase The abbreviation is not standing for official gene symbol approved by the HUGO Gene Nomenclature Committee.…”

Section: Advantages and Limitations Of Novel Urine Markersmentioning

confidence: 99%

Urine markers in monitoring for prostate cancer

Jamaspishvili

Král

Khomeriki

et al. 2009

Prostate Cancer Prostatic Dis

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The major advantages of urine-based assays are their noninvasive character and ability to monitor prostate cancer with heterogeneous foci. Almost all urine-detectable prostate-specific markers have been recently reviewed. For this reason, we focus here on only a few promising markers which have been independently evaluated (in particular PCA3, fusion genes, TERT, AMACR, GSTP1, MMP9 and VEGF) and very recent ones (ANXA3 and sarcosine). The emphasis is also on multiplex biomarker analysis and on microarray-based analysis of fusion genes. A combination of multiple urine biomarkers may be valuable in the case of men with persistently elevated serum prostatespecific antigen and a history of negative biopsies. The emerging urine tests should help in both early diagnosis of prostate cancer and identifying aggressive tumors for radical treatment.

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Detection of telomerase activity in prostate massage samples improves differentiating prostate cancer from benign prostatic hyperplasia

Cited by 23 publications

References 21 publications

Noninvasive Detection of Prostate Cancer by Quantitative Analysis of Telomerase Activity

Noninvasive Detection of Prostate Cancer by Quantitative Analysis of Telomerase Activity

Gefitinib and bicalutamide show synergistic effects in primary cultures of prostate cancer derived from androgen-dependent naive patients

Urine markers in monitoring for prostate cancer

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