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Quantitative telomerase activity in malignant, benign and normal gynecological tissues
1Department of Obstetrics and Gynecology, Turkey
2Department of Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey
*Corresponding Author(s): B. S aygan-Karamiirsel E-mail:
Objective: The aim of this study was to evaluate quantitative telomerase activity in malignant, benign and normal gynecological tissue samples by using the Telomerase-PCR ELISA kit, and to determine a cut-off level for malignancy by this quantitative method.
Materials and methods: Fifty gynecological tumors, 27 benign gynecological disorders and 29 normal tissues were analyzed by the Telomerase-PCR ELISA kit. All tissues were confirmed by a pathologist. A ROC (receiver operator characteristic) curve was drawn to determine a threshold level best discriminating malignant tissues from benign pathologies and normal tissues. Telomerase activity was compared in malignant, benign and normal tissues.
Results: The mean level of telomerase activity of the malignant tumor samples (1.03 +/- 0.53 units) was significantly (p < .001) higher than the normal tissues (0.13 +/- 0.07 units) and benign pathologies (0.37 +/- 0.25 units). The cut-off point to differentiate malignant samples from benign samples was set at 0.42 units, where the sensitivity was 93.8% and the specificity was 89.3%. Positive predictive value was 84% and negative predictive value was 89.3%. There was a significant difference in telomerase activity between malignant, benign and normal tissues within each histological group.
Conclusion: In this preliminary study, the telomerase-PCR ELISA method was found to have a high sensitivity and specificity to differentiate malignant gynecological tissues from benign tissues.
Telomerase activity; Gynecological cancers; Telomerase PCR-ELISA
B. S aygan-Karamiirsel,G. Dikmen,P. Dogan,T. Aksu,S. Guven,A. Ayhan. Quantitative telomerase activity in malignant, benign and normal gynecological tissues. European Journal of Gynaecological Oncology. 2005. 26(1);83-86.
[1] Holt S.E., Wright W.E., Shay J.W.: "Multiple pathways for the regulation of telomerase". Eur. J. Cancer, 1997, 33, 761.
[2] Dahse R., Fiedler W., Ernst G.:''Telomeres and telomerase: Biological and clinical importance". Clin. Chem., 1997, 43, 708.
[3] Muniyappa K., Kironmai K.M.: "Telomere structure, replication and length maintenance". Crit. Rev. Biochem. Mol. Biol., 1998, 33, 297.
[4] Nagai N., Murakami J., Oshita T., Ohama K., Tahara. H.: Diagnostic value of telomerase activity in gynaecological malignancies". Int. J. Gynecol. Cancer, 1998, 8, 481.
[5] Gorham H.,Y oshida K.,S ugino T., Marsh G., Manek S.,C harnock M. et al.: "Telomerase activity in human gynaecological malignancies". J. Clin. Pathol., 1997, 50, 501.
[6] Zheng P., Iwasaka T., Yamasaki F., Ouchida M.: "Telomerase activity in gynaecological tumors". Gynecol. Oncol., 1997, 64, 171.
[7] Tatsuma T., Goto S., Kitano S., Lin Y.: "Telomerase activity in peripheral blood for diagnosis of hepatoma". J. Gastroenterol. Hepatol., 2000, 15, 1064.
[8] Hess J.L., Highsmith W.E. Jr.: "Telomerase detection in body fluids". Clin. Chem., 2002, 48, 18.
[9] Shroyer K.R., Thompson L.C., Enomoto T., Eskens J.L., Shroyer A.L., McGregor J.A.: "Telomerase expression in normal epithelium, reactive atypia, squamous dysplasia and squamous cell carcinoma of the uterine cervix". AJCP, 1998, 109, 153.
[10] Cheung A.N., Zhang D.K., Liu Y., Ngan H.Y., Shen D.H., Tsao S.W.: "Telomerase activity in gestational trophoblastic disease". J. Clin. Pathol., 1999, 52, 588.
[11] Mutirangura A., Sriuranpong V., Termrunggraunglert W., Tresukosol D.: "Telomerase activity and human papillomavirus in malignant, premalignant and benign cervical lesions". Br. J. Cancer, 1998, 78, 933.
[12] Kyo S., Kanaya T., Takakura M.,Tanaka M., Yamashita A., Inoue H. et al.: "Expression of human telomerase subunits in ovarian malignant, borderline and benign tumors". Int. J. Cancer, 1999, 80, 804.
[13] Datar R.H., Naritoku W.Y., Li P., Tsao-Wei D., Groshen S., Taylor C.R. et al.: "Analysis of telomerase activity in ovarian cystadenomas, low-malignant-potential tumors and invasive carcinomas". Gynecol. Oncol., 1999, 74, 338.
[14] Shay J.W., Gazdar A.F.: "Telomerase in the early detection of cancer". J. Clin. Pathol., 1997, 50, 106.
[15] Duggan B.D., Wan M., Yu M.C., Roman L.D., Muderspach L.I., Delgadillo E. et al.: "Detection of ovarian cancer cells: comparison of a telomerase assay and cytologic examination". J. Natl. Cancer Inst., 1998, 90, 238
[16] Wang S.J., Sakamoto T., Yasuda Si S., Fukasawa I., Ota Y., Hayashi M. et al.: "The relationship between telomere length and telomerase activity in gynaecological cancers". Gynecol. Oncol., 2002, 84, 81.
[17] Sakamoto M., Toyoizumi T.,Kikuchi Y.,Okamoto A., Nakayama H.,A oki D. et al.:" Telomerase activity in gynaecological tumors". Oncol. Rep., 2000, 7, 1003.
[18] Yokoyama Y., Takahashi Y., Shinohara A., Lian Z., Tamaya T.: "Telomerase activity in the female reproductive tract and neoplasms". Gynecol. Oncol., 1998, 68, 145.
[19] Kyo S., Takakura M., Kohama T., Inoue M.: "Telomerase activity in human endometrium". Cancer Res., 1997, 57, 610.
[20] Counter C.M., Hirte H.W., Bacchetti S., Harley C.B.: "Telomerase activity in human ovarian carcinoma". P roc. Natl. Acad. Sci USA, 1994, 91, 2900.
[21] Kim N.W., P iatyszek M., P rowse K., Harley C.: "Specific association of human telomerase activity with immortal cells and cancer". Science, 1994, 266, 2011.
[22] Hess L.J., Highsmith E.W.: "Telomerase detection in body fluids". Clin. Chem., 2002, 48, 18 .
[23] Shay J.W., Bacchetti S.: "A survey of telomerase activity in human cancer". Eur. J. Cancer, 1997, 33, 787.
[24] Wu Y.Y., Hruszkewycz A., Delgado R., Yang A.: "Limitations on the quantitative determination of telomerase activity by the electrophoretic and ELISA based TRAP assays". Clinica Chimica Acta, 2000, 293, 199.
[25] Uehara H., Nardone G., Nazarenko I., Hohman R.J.: "Detection of telomerase activity utilizing energy transfer primers: comparison with gel- and ELISA-based detection". Biotechniques, 1999, 26, 552.
[26] Bradford M.M.: "A rapid sensitive method for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding". Anal. Biochem., 1976, 72, 248.
[27] Lundblad V., Wright W.: "Telomeres and telomerase: A simple picture becomes complex". Cell., 1996, 87, 369.
[28] Pao C.C.,T seng C.J.,L in C.Y.,Y ang F.P.,H or J.J.,Y ao D.S. et al.: "Differential expression of telomerase activity in human cervical cancer and cervical intraepithelial neoplasia lesions". J. Clin. Oncol., 1997, 15, 1932.
[29] Burger A.M., Bibby M.C., Double J.A.: "Telomerase activity in malignant and somatic mammalian tissues". Br. J. Cancer, 1997, 75, 516.
[30] Streutker C.J., Thomer P., Fabricius N., Weitzman S.: "Telomerase activity as a prognostic factor in neuroblastomas". Pediatr. Dev. Pathol., 2001, 4, 62.
[31] Colgin L.M., Reddel R.R .: "Telomere maintenance mechanisms and cellular immortalization". Curr. Opin. Genet. Dev., 1999, 9, 97.
[32] Shay J.W., Wright W.E.: "Telomerase: A target for cancer therapeutics". Cancer Cell., 2002, 2, 257.
[33] Ebina Y., Yamada H., Fujino T., Furuta I., Sakuragi N., Yamamoto R. et al.: "Telomerase activity correlates with histopathological factors in uterine endometrial carcinoma". Int. J. Cancer, 1999, 84, 529.
[34] Sakamoto M.,T oyoizumi T., Kikuchi Y.,O kamoto A., Nakayama H. Aoki D. et al.: "Telomerase activity in gynaecologicalal tumors". Oncol. Rep., 2000, 7, 1003.
[35] Kiyozuka Y., Yamamoto D., Yang J., Vemura Y., Senzaki H., Adachi S. et al.: "Correlation of chemosensitivity to anticancer drugs and telomere length, telomerase activity and telomerase RNA expression in human ovarian cancer cells". Anticancer Res., 2000, 20, 203.
[36] Villa R., Folini M., P erego P., Supino R., Setti E., Daidone M.G. et al.: "Telomerase activity and telomere length in human ovarian cancer and melanoma cell lines: correlation with sensitivity to DNA damaging agents". Int. J. Oncol., 2000,16, 995.
[37] Yokoyama Y., Takahashi Y., Shinohara A., Lian Z., Wan X., Niwa K. et al.: "Attenuation of telomerase activity by a hammerhead ribozyme targeting the template region of telomerase RNA in endometrial carcinoma cells". Cancer Res., 1998, 58, 5406.
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