Telomerase Activity in Benign and Malignant Epithelial Ovarian Tumors

Wan, Minghong; Li, Weizhi; Felix, Janine F.; Zhao, Yanle; Dubeau, Louis; Duggan, B.

doi:10.1093/jnci/89.6.437

Cited by 43 publications

(25 citation statements)

References 19 publications

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“…Usually, there is no detectable telomerase activity in normal ovarian tissue. In benign ovarian pathologies such as mucinous cyst adenoma, the positivity of telomerase activity was found to be between 0% and 36.3% in association with proliferation (19)(20)(21)(22). In the same trials, 67% to 100% telomerase activity was detected in borderline tumors.…”

Section: Discussionmentioning

confidence: 83%

The Status of Telomerase Enzyme Activity in Benign and Malignant Gynaecologic Pathologies

Gül¹,

Dündar²,

Bodur³

et al. 2013

Balkan Med J

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Background: Telomeres are essential for the function and stability of eukaryotic chromosomes. Telomerase consists of three subunits: human telomerase reverse transcriptase (hTERT), human telomerase RNA (hTR), and telomerase protein 1 (TP1). The hTERT subunit determines the activity of telomerase as an enzyme and is detected in most human tumors and regenerative cells. Telomerase activity is a useful cancer-cell detecting marker in some types of cancers.Aims: The aim of this study was to assess of telomerase hTERT mRNA in gynaecological tumors for diagnosis of malignancy.Study Design: Cross-sectional study.Methods: A total of 55 gynaecologic tumor samples (35 ovarian, 13 endometrial, 6 cervical and 1 placental site trophoblastic tumor tissue) were obtained at the time of surgery. Quantification of hTERT mRNA was performed in a real-time reverse transcriptase polymerase chain reaction (RT-PCR) using the LightCycler TeloTAGGG hTERT Quantification Kit.Results: It was histopathologically detected that 18 of the tissue samples were malignant and 37 of the samples were benign. 16 of the malignant tissue samples (88.9%) and 3 (8.1%) (endometrial tissue in proliferative phase, mucinous cyst adenoma and endometriosis) of the benign tissue samples were found to be hTERT positive. With the presence of these data, sensitivity and specificity of hTERT for the diagnosis of malignancy were calculated to be 88.9% and 91.9%, respectively. Conclusion:It was suggested that the measurement of telomerase activity in gynaecologic tumors, except for endometrial tissue in the reproductive phase, is a valuable method for pathological investigation.

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Section: Discussionmentioning

confidence: 83%

The Status of Telomerase Enzyme Activity in Benign and Malignant Gynaecologic Pathologies

Gül¹,

Dündar²,

Bodur³

et al. 2013

Balkan Med J

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“…Most LMP tumours express telomerase in vivo, providing an additional argument in support of the notion that they represent a stage of malignant transformation that is distinct from cystadenomas (Wan et al, 1997). Given that telomere attrition is thought to be associated with structural chromosomal instability that can be overcome by telomerase (Counter et al, 1992;Artandi et al, 2000;O'Hagan et al, 2002), one may question whether the increased stability observed in our cultured LMP tumour cells could have been due to varying levels of telomerase expression.…”

Section: Discussionmentioning

confidence: 64%

“…For example, although somatic loss of heterozygosity, a hallmark of malignancy, has been occasionally observed in LMP tumours, it is clear that such events are not only rare in these tumours, but are also not essential to their development (Cheng et al, 1996). On the other hand, LMP tumours usually express telomerase (Wan et al, 1997), a feature of the malignant phenotype, and global DNA methylation changes (Cheng et al, 1997) or changes in the DNA methylation status of centromeric and juxtacentromeric sequences (Qu et al, 1999) in these tumours are more similar to those in carcinomas than in cystadenomas. Although these results strengthen the notion that LMP tumours are intermediate between benign and frankly malignant ovarian epithelial tumours, they shed little light on their underlying mechanisms.…”

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confidence: 99%

Increased chromosomal stability in cultures of ovarian tumours of low malignant potential compared to cystadenomas

Douglas

Brockmeyer

et al. 2007

Br J Cancer

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Cell cultures of ovarian cystadenomas transfected with SV40 large T antigen are not immortal because they invariably reach a phenomenon called crisis, which is triggered in part by telomere attrition. Recovery from crisis may be an integral component of the malignant transformation process. We reported earlier that such ovarian cystadenoma cell cultures undergo severe changes in DNA ploidy as they approach crisis and that such changes are an important determinant of crisis independent of telomere attrition. Here, we show that in sharp contrast to these benign ovarian tumours, the DNA content of ovarian tumours of low malignant potential (LMP) was remarkably stable as they approached crisis, suggesting that telomere attrition was the main determinant of this mortality checkpoint. Lack of a ploidy-based crisis was not due to loss of expression of a functional SV40 large T antigen protein. We conclude that ovarian LMP tumours are characterised by increased numerical chromosomal stability compared to cystadenomas. This might account for the fact that most LMP tumours are diploid or near diploid in vivo. This fundamental difference in chromosomal stability between ovarian cystadenomas and LMP tumours also suggests potential differences in predisposition to progression to malignancy between these two ovarian tumour subtypes.

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“…Cell pellets from peritoneal washings were lysed and tested for the presence or absence of telomerase activity using the telomerase repeat amplification protocol (TRAP; Ref. 23) assay as described previously (25). The reaction products were electrophoresed on 8% polyacrylamide and visualized by autoradiography.…”

Section: Methodsmentioning

confidence: 99%

“…Each assay was performed in parallel with two control reactions, one in which the assay was preceded by digestion of the sample with RNase A (catalog number R5503; Sigma Chemical Co., St. Louis, MO) at a final concentration of 0.05 mg/ml, and another in which 1 l of a cell lysate previously shown to contain high levels of telomerase activity was added to the test sample. A sample was not scored as positive unless the RNase A-treated control showed complete absence of telomerase products because telomerase is a riboprotein that is inactivated by RNase A. Conversely, a sample was not scored as negative unless products were detected after addition of a telomerase-positive extract to that sample (25).…”

Section: Methodsmentioning

confidence: 99%

Detection of Residual Subclinical Ovarian Carcinoma after Completion of Adjuvant Chemotherapy

Nouriani

Bahador

Berek

et al. 2004

Clinical Cancer Research

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Purpose:We sought to test the hypothesis that the presence of telomerase activity in peritoneal washings of patients treated for ovarian carcinoma is a sensitive and specific indicator of the presence of residual disease. We hypothesized that this test, if added to second-look procedure protocols, could help determine whether residual disease is present or not in patients who have completed their adjuvant chemotherapy for ovarian carcinoma.Experimental Design: Peritoneal washings were obtained from 100 consecutive patients undergoing a secondlook procedure after treatment for ovarian carcinoma (cases) and from 100 patients undergoing surgery for benign gynecological conditions (controls). The washings were assayed for telomerase activity using the telomerase repeat amplification protocol. The results were compared to the histological and cytological findings.Results: Among our 100 cases, 82 (82%) had either positive second-look procedures or expressed telomerase in their peritoneal washings. Fifty-three (53%) had positive second-look procedures, whereas 66 (66%) tested positive for telomerase. Twenty-nine of the 47 patients (62%) with negative second-look procedures tested positive for telomerase. Of the 53 patients with positive second-look procedures, 37 (70%) tested positive for telomerase. None of the 100 controls (0%) expressed telomerase in their peritoneal washings.Conclusions: Telomerase activity in peritoneal washings of patients treated for ovarian carcinoma and undergoing a second-look procedure may provide a means of increasing the sensitivity of such procedures for the detection of residual disease while maintaining a high level of specificity.

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Telomerase Activity in Benign and Malignant Epithelial Ovarian Tumors

Cited by 43 publications

References 19 publications

The Status of Telomerase Enzyme Activity in Benign and Malignant Gynaecologic Pathologies

The Status of Telomerase Enzyme Activity in Benign and Malignant Gynaecologic Pathologies

Increased chromosomal stability in cultures of ovarian tumours of low malignant potential compared to cystadenomas

Detection of Residual Subclinical Ovarian Carcinoma after Completion of Adjuvant Chemotherapy

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