Cell proliferation rate and telomerase activity in the differential diagnosis between benign and malignant mesothelial proliferations

Çakır, Çağlar; Güllüoğlu, Mine; Yılmazbayhan, Dilek

doi:10.1080/00313020500456017

Cited by 15 publications

(12 citation statements)

References 39 publications

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“…Clinically, sarcomatoid tumours tend to be more aggressive than epithelioid tumours (Herndon et al, 1998). In RPMI medium, A recent report on cell proliferation rates in samples of mesothelioma, using the Ki-67 proliferation index (PI), showed that biphasic tumours had a higher PI than epithelioid and sarcomatoid types, and that the median value for epithelioid samples was higher than that of sarcomatoid tumours (Cakir et al, 2006), although only 4.5% of tumours were of the sarcomatoid type. In all cell lines in which a GI 50 value was reached, this value was lower when DFBS, rather than normal FBS, was used in the medium.…”

Section: Discussionmentioning

confidence: 99%

The role of folate receptor alpha (FRα) in the response of malignant pleural mesothelioma to pemetrexed-containing chemotherapy

et al. 2010

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BACKGROUND: The standard treatment of choice for malignant pleural mesothelioma is chemotherapy with pemetrexed and platinum, but the clinical outcome is poor. This study investigates the response to pemetrexed in a panel of eight mesothelioma cell lines and the clinical outcome for patients treated with pemetrexed in relation to folate receptor alpha (FRa). METHODS: Cell lines were treated with pemetrexed to determine the concentration that reduced growth to 50% (GI 50 ). FRa expression was determined by western blotting and that of FRa, reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) by real-time quantitative RT -PCR. Immunohistochemistry for FRa was carried out on 62 paraffin-embedded samples of mesothelioma from patients who were subsequently treated with pemetrexed. RESULTS: A wide range of GI 50 values was obtained for the cell lines, H2452 cells being the most sensitive (GI 50 22 nM) and RS5 cells having a GI 50 value greater than 10 mM. No FRa protein was detected in any cell line, and there was no relationship between sensitivity and expression of folate transporters. FRa was detected in 39% of tumour samples, generally in a small percentage of cells. There was no correlation between the presence of FRa and the outcome of pemetrexed treatment, and no significant difference between histological subtypes. CONCLUSION: Response to treatment with pemetrexed does not depend on the presence of FRa.

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Section: Discussionmentioning

confidence: 99%

The role of folate receptor alpha (FRα) in the response of malignant pleural mesothelioma to pemetrexed-containing chemotherapy

et al. 2010

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“…29,30 The hTERT protein has been demonstrated in all grades of cervical dysplasia, whereas TRAP has revealed telomerase activity only in high-grade lesions. 18 Dhaene et al 31 found no enzyme activity in mesothelial cell lines with TRAP, but they could demonstrate hTERT mRNA, 32 and Cakir et al 33 found immunohistochemical hTERT reactivity in mesothelial cells in 7 of 22 benign effusions.…”

Section: Discussionmentioning

confidence: 99%

Comparison of NCL-hTERT Antibody Reactivity and Telomere Repeat Amplification Protocol in Situ in Effusions

Zendehrokh

Rehnberg²,

Dejmek

2007

Acta Cytologica

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“…It is known that TA is expressed in more than 90% of malignant pleural mesotheliomas (25), and the enzyme activity and hTERT expression have been proposed for differential diagnosis in mesothelial lesions (26). However, no information is available thus far concerning the presence of telomere maintenance mechanisms in DMPM.…”

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confidence: 99%

Multiple Mechanisms of Telomere Maintenance Exist and Differentially Affect Clinical Outcome in Diffuse Malignant Peritoneal Mesothelioma

Villa¹,

Daidone²,

Motta³

et al. 2008

Clinical Cancer Research

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Purpose: This study aims to investigate the prevalence of the two known telomere maintenance mechanisms, telomerase activity (TA) and alternative lengthening of telomeres (ALT), and to assess their prognostic relevance in diffuse malignant peritoneal mesothelioma (DMPM). Experimental Design: In 44 DMPM specimens obtained from 38 patients, TA was determined using the telomeric repeat amplification protocol and ALT was detected by assaying ALT-associated promyelocytic leukemia nuclear bodies. The prognostic significance of telomere maintenance mechanisms was analyzed by Cox regression in the overall series and in a subset of 29 patients who underwent a uniform treatment regimen consisting of cytoreductive surgery and hyperthermic i.p. chemotherapy. Results: Telomere maintenance mechanisms were detectable in 86.4% of DMPM: ALT or TA alone was found in 18.2% or 63.6% of lesions, respectively, whereas two cases (4.6%) were ALT+/TA+. TA and ALT proved to be inversely associated (P = 0.002). In the overall series, TA was prognostic for 4-year relapse (TA+ versus TA-, hazard ratio, 3.30; 95% confidence interval, 1.23-8.86; P = 0.018) and cancer-related death (TA+ versusTA-, hazard ratio, 3.56; 95% confidence interval, 1.03-12.51; P = 0.045), whereas ALT failed to significantly affect clinical outcome. These results held true also in the subset of patients submitted to uniform treatment with cytoreductive surgery and hyperthermic i.p. chemotherapy. Conclusions: Our results indicate that both known telomere maintenance mechanisms,TA and ALT, are present in DMPM and differentially affect patient prognosis.

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Cell proliferation rate and telomerase activity in the differential diagnosis between benign and malignant mesothelial proliferations

Cited by 15 publications

References 39 publications

The role of folate receptor alpha (FRα) in the response of malignant pleural mesothelioma to pemetrexed-containing chemotherapy

The role of folate receptor alpha (FRα) in the response of malignant pleural mesothelioma to pemetrexed-containing chemotherapy

Comparison of NCL-hTERT Antibody Reactivity and Telomere Repeat Amplification Protocol in Situ in Effusions

Multiple Mechanisms of Telomere Maintenance Exist and Differentially Affect Clinical Outcome in Diffuse Malignant Peritoneal Mesothelioma

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