Skip to main content
Erschienen in: Medical Oncology 1/2011

01.03.2011 | Original Paper

Prognostic significance of telomerase activity and some tumor markers in non-small cell lung cancer

verfasst von: Maha Hashim, Magda Sayed, Nervana Samy, Salah Elshazly

Erschienen in: Medical Oncology | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

The prognosis of non small cell lung cancer (NSCLC) has remained disappointing over the last decades even in localized stages. Numerous prognostic factors have been investigated which might select patients for additional treatment. The objective of the current study was to assess the prognostic significance of telomerase activity, serum anti-p53 antibodies (anti-p53a), c-erbB-2 and CEA in patients with NSCLC. The study included 60 patients with histological proven NSCLC besides 60 controls (30 smokers and 30 nonsmokers). Patients were divided into four stages according to their histopathology. All patients were subjected to; determination of telomerase activity by telomeric repeat amplification protocol (TRAP) assay in tumor tissue specimens and adjacent normal lung tissues, also, determination of preoperative serum anti-p53a, c-erbB-2 and CEA. Telomerase activity was detected in 40 of 60 (66.6%) of NSCLC tissue specimens using the TRAP assay. As regard the stages, telomerase activity was positive in 5 of 15 patients (33.3%) with stage I NSCLC, in 11 of 20 patients (55%) with stage II NSCLC, in 9 of 10 patients (90%) with stage III NSCLC and in all patients (100%) with stage IV NSCLC. More cases of positive telomerase activity were observed in the group with advanced disease and in the group with poorly differentiated tumors. Telomerase activity was not detected in any normal lung tissue. The concentrations of serum anti-p53a, c-erbB-2, CEA were significantly higher in patients with NSCLC in comparison to the smoker and nonsmoker controls and their levels increased according to the stage of disease. Logistic regression test showed a relation between telomerase positivity and anti- p53a but no relation with c-erbB2, CEA. Telomerase activity was detected in most of NSCLC tissues; it was detected more frequently in advanced disease than early-stage disease. Anti-p53, c-erbB-2 and CEA were significantly higher in patients with NSCLC than controls and this increment was more evident in late stages of the disease. So, these biological markers might be useful predictors of prognosis. They may be helpful in defining groups of patients with NSCLC who could benefit from adjuvant treatments, also these markers can be used as therapeutic targets.
Literatur
1.
Zurück zum Zitat Duarte RL, Paschoal ME. Molecular markers in lung cancer: prognostic role and relationship to smoking. J Bras Pneumol. 2006;32(1):56–65.PubMedCrossRef Duarte RL, Paschoal ME. Molecular markers in lung cancer: prognostic role and relationship to smoking. J Bras Pneumol. 2006;32(1):56–65.PubMedCrossRef
2.
Zurück zum Zitat Borras C, Esteve JM, Vin JR, Sastre J, Vin J, Pallardo FV. Glutathione regulates telomerase activity in 3T3 fibroblasts. J Biol Chem. 2004;279:34332–5.PubMedCrossRef Borras C, Esteve JM, Vin JR, Sastre J, Vin J, Pallardo FV. Glutathione regulates telomerase activity in 3T3 fibroblasts. J Biol Chem. 2004;279:34332–5.PubMedCrossRef
3.
Zurück zum Zitat Gertler R, Rosenberg R, Stricker D, Friederichs J, Hoos A, Werner M, et al. Telomere Length and Human Telomerase Reverse Transcriptase expression as markers for progression and prognosis of colorectal carcinoma. J Clin Oncol. 2004;22:1807–14.PubMedCrossRef Gertler R, Rosenberg R, Stricker D, Friederichs J, Hoos A, Werner M, et al. Telomere Length and Human Telomerase Reverse Transcriptase expression as markers for progression and prognosis of colorectal carcinoma. J Clin Oncol. 2004;22:1807–14.PubMedCrossRef
4.
Zurück zum Zitat Piatyszek MA, Kim SL, Weinrich SL. Detection of telomerase activity in human cells and tumors by a telomeric repeat amplification protocol (TRAP). Methods Cell Sci. 1995;17:1–15.CrossRef Piatyszek MA, Kim SL, Weinrich SL. Detection of telomerase activity in human cells and tumors by a telomeric repeat amplification protocol (TRAP). Methods Cell Sci. 1995;17:1–15.CrossRef
5.
Zurück zum Zitat Iniesta P, González-Quevedo R, Morán A, García-Aranda C, de Juan C, Sánchez-Pernaute A, et al. Relationship between 3p deletions and telomerase activity in non-small-cell lung cancer: prognostic implications. Br J Cancer. 2004;90(10):1983–8.PubMedCrossRef Iniesta P, González-Quevedo R, Morán A, García-Aranda C, de Juan C, Sánchez-Pernaute A, et al. Relationship between 3p deletions and telomerase activity in non-small-cell lung cancer: prognostic implications. Br J Cancer. 2004;90(10):1983–8.PubMedCrossRef
6.
Zurück zum Zitat Poposka BI, Smickova S, Crvenkovska SJ, Ivanovska BZ, Stefanovski T, Metodieva M, et al. Prognostic value of the expression of p53 in patients with non-small Cell lung cancer. Macedonian J Med Sci. 2009;2(4):335–40.CrossRef Poposka BI, Smickova S, Crvenkovska SJ, Ivanovska BZ, Stefanovski T, Metodieva M, et al. Prognostic value of the expression of p53 in patients with non-small Cell lung cancer. Macedonian J Med Sci. 2009;2(4):335–40.CrossRef
7.
Zurück zum Zitat Gebitekin C, Bayram AS, Tunca B, Balaban SA. Clinical significance of p53 gene mutation in T1–2 N0 non-small cell lung cancer. Asian Cardiovasc Thorac Ann. 2007;15(1):35–8.PubMed Gebitekin C, Bayram AS, Tunca B, Balaban SA. Clinical significance of p53 gene mutation in T1–2 N0 non-small cell lung cancer. Asian Cardiovasc Thorac Ann. 2007;15(1):35–8.PubMed
8.
Zurück zum Zitat Schlichtholz B, Tradaniel J, Lubin R, Zalcman G, Hirsch A, Soussi T. Analyses of p53 antibodies in sera of patients with lung carcinoma define immunodominant regions in the p53 protein. Br J Cancer. 1994;69:809–16.PubMedCrossRef Schlichtholz B, Tradaniel J, Lubin R, Zalcman G, Hirsch A, Soussi T. Analyses of p53 antibodies in sera of patients with lung carcinoma define immunodominant regions in the p53 protein. Br J Cancer. 1994;69:809–16.PubMedCrossRef
9.
Zurück zum Zitat Meert AP, Martin B, Paesmans M. The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature. Br J Cancer. 2003;89:959–65.PubMedCrossRef Meert AP, Martin B, Paesmans M. The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature. Br J Cancer. 2003;89:959–65.PubMedCrossRef
10.
Zurück zum Zitat Shigematsu H, Takahashi T, Nomura M. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res. 2005;65:1642–6.PubMedCrossRef Shigematsu H, Takahashi T, Nomura M. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res. 2005;65:1642–6.PubMedCrossRef
11.
Zurück zum Zitat Nakamura H, Kawasaki N, Taguchi M, Kabasawa K. Association of HER-2 overexpression with prognosis in nonsmall cell lung carcinoma: a metaanalysis. Cancer. 2005;103:1865–73.PubMedCrossRef Nakamura H, Kawasaki N, Taguchi M, Kabasawa K. Association of HER-2 overexpression with prognosis in nonsmall cell lung carcinoma: a metaanalysis. Cancer. 2005;103:1865–73.PubMedCrossRef
12.
Zurück zum Zitat Salgia R, David H, James EH, Evan P, Anthony E, Arthur TS. Role of serum tumor markers Ca 125 and CEA in non-small cell lung cancer. Anticancer Res. 2001;21:1241–6.PubMed Salgia R, David H, James EH, Evan P, Anthony E, Arthur TS. Role of serum tumor markers Ca 125 and CEA in non-small cell lung cancer. Anticancer Res. 2001;21:1241–6.PubMed
13.
Zurück zum Zitat Sawabata N, Ohta M, Takeda S. Serum carcinoembryonic antigen level in surgically resected clinical stage I patients with non-small cell lung cancer. Ann Thorac Surg. 2002;74:174–9.PubMedCrossRef Sawabata N, Ohta M, Takeda S. Serum carcinoembryonic antigen level in surgically resected clinical stage I patients with non-small cell lung cancer. Ann Thorac Surg. 2002;74:174–9.PubMedCrossRef
14.
Zurück zum Zitat Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1710–7.PubMedCrossRef Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1710–7.PubMedCrossRef
15.
Zurück zum Zitat Kim NW, Piatyszek MA, Prowse KR. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266:2011–5.PubMedCrossRef Kim NW, Piatyszek MA, Prowse KR. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266:2011–5.PubMedCrossRef
16.
Zurück zum Zitat Wright WE, Shay JW, Piatyszek MA. Modification of a telomeric repeat amplification protocol (TRAP) result in increased reliability, linearity, and sensitivity. Nucleic Acids Res. 1995;23:3794–5.PubMedCrossRef Wright WE, Shay JW, Piatyszek MA. Modification of a telomeric repeat amplification protocol (TRAP) result in increased reliability, linearity, and sensitivity. Nucleic Acids Res. 1995;23:3794–5.PubMedCrossRef
17.
Zurück zum Zitat Urquidi V, Tarin D, Goodison S. Role of telomerase in cell senescence and oncogenesis. Annu Rev Med. 2000;51:65–79.PubMedCrossRef Urquidi V, Tarin D, Goodison S. Role of telomerase in cell senescence and oncogenesis. Annu Rev Med. 2000;51:65–79.PubMedCrossRef
18.
Zurück zum Zitat Morales CP, Holt SE, Ouellette M. Absence of cancer-associated changes in human fibroblasts immortalized with telomerase. Nat Genet. 1999;21:115–8.PubMedCrossRef Morales CP, Holt SE, Ouellette M. Absence of cancer-associated changes in human fibroblasts immortalized with telomerase. Nat Genet. 1999;21:115–8.PubMedCrossRef
19.
Zurück zum Zitat Hahn WC, Counter CM, Lundberg AS. Creation of human tumor cells with defined genetic elements. Nature. 1999;400:464–8.PubMedCrossRef Hahn WC, Counter CM, Lundberg AS. Creation of human tumor cells with defined genetic elements. Nature. 1999;400:464–8.PubMedCrossRef
20.
Zurück zum Zitat Taga S, Osaki T, Ohgami A. Prognostic impact of telomerase activity in non–small-cell lung cancers. Ann Surg. 1999;230:715–20.PubMedCrossRef Taga S, Osaki T, Ohgami A. Prognostic impact of telomerase activity in non–small-cell lung cancers. Ann Surg. 1999;230:715–20.PubMedCrossRef
21.
Zurück zum Zitat Lantuejoul S, Salon C, Soria JC, Brambilla E. Telomerase expression in lung preneoplasia and neoplasia. Int J Cancer. 2007;120:1835–41.PubMedCrossRef Lantuejoul S, Salon C, Soria JC, Brambilla E. Telomerase expression in lung preneoplasia and neoplasia. Int J Cancer. 2007;120:1835–41.PubMedCrossRef
22.
Zurück zum Zitat Blanco D, Vicent S, Fraga MF. Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway. Neoplasia. 2007;9:840–52.PubMedCrossRef Blanco D, Vicent S, Fraga MF. Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway. Neoplasia. 2007;9:840–52.PubMedCrossRef
23.
Zurück zum Zitat González-Quevedo R, Iniesta P, Morán A, Juan CD, Sánchez-Pernaute A, Fernández C, et al. Cooperative role of telomerase activity and p16 expression in the prognosis of non–small-cell lung cancer. J Clin Oncol. 2002;20(1):254–62.PubMedCrossRef González-Quevedo R, Iniesta P, Morán A, Juan CD, Sánchez-Pernaute A, Fernández C, et al. Cooperative role of telomerase activity and p16 expression in the prognosis of non–small-cell lung cancer. J Clin Oncol. 2002;20(1):254–62.PubMedCrossRef
24.
Zurück zum Zitat Targowski T, Jahnz-Rózyk K, Szkoda T, Płusa T, From S. Telomerase activity in transthoracic fine-needle biopsy aspirates from non-small cell lung cancer as prognostic factor of patients’ survival. Lung Cancer. 2008;61(1):97–103.PubMedCrossRef Targowski T, Jahnz-Rózyk K, Szkoda T, Płusa T, From S. Telomerase activity in transthoracic fine-needle biopsy aspirates from non-small cell lung cancer as prognostic factor of patients’ survival. Lung Cancer. 2008;61(1):97–103.PubMedCrossRef
25.
Zurück zum Zitat Chen KY, Lee LN, Yu CJ, Lee YC, Kuo SH, Yang PC. Elevation of telomerase activity positively correlates to poor prognosis of patients with non-small cell lung cancer. Cancer Lett. 2006;240(1):148–56.PubMedCrossRef Chen KY, Lee LN, Yu CJ, Lee YC, Kuo SH, Yang PC. Elevation of telomerase activity positively correlates to poor prognosis of patients with non-small cell lung cancer. Cancer Lett. 2006;240(1):148–56.PubMedCrossRef
26.
Zurück zum Zitat Jung JH, Lee CJ, Yoo GP, Lee KY. The Expression of Telomerase Reverse Transcriptase Protein is an Independent Prognostic Marker in Early Stage Non-Small Cell Lung Carcinomas. Korean J Pathol. 2007;41:95–102. Jung JH, Lee CJ, Yoo GP, Lee KY. The Expression of Telomerase Reverse Transcriptase Protein is an Independent Prognostic Marker in Early Stage Non-Small Cell Lung Carcinomas. Korean J Pathol. 2007;41:95–102.
28.
Zurück zum Zitat Steels E, Paesmans M, Berghmans T, Branle F, Lemaitre F, Mascaux C, et al. Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J. 2001;18:705–19.PubMedCrossRef Steels E, Paesmans M, Berghmans T, Branle F, Lemaitre F, Mascaux C, et al. Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J. 2001;18:705–19.PubMedCrossRef
29.
Zurück zum Zitat Laudanski J, Niklinska W, Burzykowski T, Chyczewski L, Niklinski J. Prognostic significance of p53 and bcl-2 abnormalities in operable non-small cell lung cancer. Eur Respir J. 2001;17:660–6.PubMedCrossRef Laudanski J, Niklinska W, Burzykowski T, Chyczewski L, Niklinski J. Prognostic significance of p53 and bcl-2 abnormalities in operable non-small cell lung cancer. Eur Respir J. 2001;17:660–6.PubMedCrossRef
30.
Zurück zum Zitat Murray PV, Soussi T, O’Brien MER, Smith IE, Brossault S, Norton A, et al. Serum p53 antibodies: predictors of survival in small-cell lung cancer? Br J Cancer. 2000;83:1418–24.PubMedCrossRef Murray PV, Soussi T, O’Brien MER, Smith IE, Brossault S, Norton A, et al. Serum p53 antibodies: predictors of survival in small-cell lung cancer? Br J Cancer. 2000;83:1418–24.PubMedCrossRef
31.
Zurück zum Zitat Lai CL, Tsai CM, Tsai TT, Kuo BI, Chang KT, Fu HT, et al. Presence of serum anti-p53 antibodies is associated with pleural effusion and poor prognosis in lung cancer patients. Clin Cancer Res. 1998;4(12):3025–30.PubMed Lai CL, Tsai CM, Tsai TT, Kuo BI, Chang KT, Fu HT, et al. Presence of serum anti-p53 antibodies is associated with pleural effusion and poor prognosis in lung cancer patients. Clin Cancer Res. 1998;4(12):3025–30.PubMed
32.
Zurück zum Zitat Ohmura Y, Aoe M, Andou A, Shimizu N. Telomerase activity and Bcl-2 expression in non-small cell lung cancer. Clin Cancer Res. 2000;6(8):2980–7.PubMed Ohmura Y, Aoe M, Andou A, Shimizu N. Telomerase activity and Bcl-2 expression in non-small cell lung cancer. Clin Cancer Res. 2000;6(8):2980–7.PubMed
33.
Zurück zum Zitat Maniwa Y, Yoshimura M, Obayashi C, Inaba M, Kiyooka K, Kanki M, et al. Association of p53 Gene Mutation and Telomerase Activity in Resectable Non-Small Cell. Lung Cancer Chest. 2001;120:589–94. Maniwa Y, Yoshimura M, Obayashi C, Inaba M, Kiyooka K, Kanki M, et al. Association of p53 Gene Mutation and Telomerase Activity in Resectable Non-Small Cell. Lung Cancer Chest. 2001;120:589–94.
34.
Zurück zum Zitat Perera SA, Maser RS, Xia H. Telomere dysfunction promotes genome instability and metastatic potential in a K-ras p53 mouse model of lung cancer. Carcinogenesis. 2008;29:747–53.PubMedCrossRef Perera SA, Maser RS, Xia H. Telomere dysfunction promotes genome instability and metastatic potential in a K-ras p53 mouse model of lung cancer. Carcinogenesis. 2008;29:747–53.PubMedCrossRef
35.
Zurück zum Zitat Abdel Salam I, Gaballa HE, Abdel Wahab N. Serum levels of epidermal growth factor and HER-2 neu in non small-cell lung cancer: prognostic correlation. Med Oncol. 2009;26(2):161–6.PubMedCrossRef Abdel Salam I, Gaballa HE, Abdel Wahab N. Serum levels of epidermal growth factor and HER-2 neu in non small-cell lung cancer: prognostic correlation. Med Oncol. 2009;26(2):161–6.PubMedCrossRef
36.
Zurück zum Zitat Ardizzoni A, Cafferata MA, Paganuzzi M, Filiberti R, Marroni P, Neri M, et al. Study of pretreatment serum levels of HER-2/neu oncoprotein as a prognostic and predictive factor in patients with advanced nonsmall cell lung carcinoma. Cancer. 2001;92(7):1896–904.PubMedCrossRef Ardizzoni A, Cafferata MA, Paganuzzi M, Filiberti R, Marroni P, Neri M, et al. Study of pretreatment serum levels of HER-2/neu oncoprotein as a prognostic and predictive factor in patients with advanced nonsmall cell lung carcinoma. Cancer. 2001;92(7):1896–904.PubMedCrossRef
37.
Zurück zum Zitat Micke P, Georg Hengstler J, Ros R, Bittinger F, Metz T, Gebhard S, et al. c-erbB-2 Expression in small-cell lung cancer is associated with poor prognosis. Int J Cancer. 2001;15(4):469–618. Micke P, Georg Hengstler J, Ros R, Bittinger F, Metz T, Gebhard S, et al. c-erbB-2 Expression in small-cell lung cancer is associated with poor prognosis. Int J Cancer. 2001;15(4):469–618.
38.
Zurück zum Zitat Ochiai A, Akimoto S, Kanai Y, Shibata T, Oyama T, Hirohashi S. c-erbB-2 gene product associates with catenins in human cancer cells. Biochem Biophys Res Commun. 1994;205(1):73–8.PubMedCrossRef Ochiai A, Akimoto S, Kanai Y, Shibata T, Oyama T, Hirohashi S. c-erbB-2 gene product associates with catenins in human cancer cells. Biochem Biophys Res Commun. 1994;205(1):73–8.PubMedCrossRef
39.
Zurück zum Zitat Tateishi M, Ishida T, Mitsudomi T, Kaneko S, Sugimachi K. Prognostic value of c-erbB-2 protein expression in human lung adenocarcinoma and squamous cell carcinoma. Eur J Cancer. 1991;27:1372–5.PubMedCrossRef Tateishi M, Ishida T, Mitsudomi T, Kaneko S, Sugimachi K. Prognostic value of c-erbB-2 protein expression in human lung adenocarcinoma and squamous cell carcinoma. Eur J Cancer. 1991;27:1372–5.PubMedCrossRef
40.
Zurück zum Zitat Giatromanolaki A, Koukourakis MI, O’Byrne K, Kaklamanis L, Dicoglou C, Trichia E, et al. Non-small cell lung cancer: c-erbB-2 overexpression correlates with low angiogenesis and poor prognosis. Anticancer Res. 1996;16:3819–25.PubMed Giatromanolaki A, Koukourakis MI, O’Byrne K, Kaklamanis L, Dicoglou C, Trichia E, et al. Non-small cell lung cancer: c-erbB-2 overexpression correlates with low angiogenesis and poor prognosis. Anticancer Res. 1996;16:3819–25.PubMed
41.
Zurück zum Zitat Hsu WH, Huang CS, Hsu HS, Huang WJ, Lee HC, Huang MD, et al. Preoperative serum carcinoembryonic antigen level is a prognostic factor in women with early non–small-cell lung cancer. Ann Thorac Surg. 2007;83:419–24.PubMedCrossRef Hsu WH, Huang CS, Hsu HS, Huang WJ, Lee HC, Huang MD, et al. Preoperative serum carcinoembryonic antigen level is a prognostic factor in women with early non–small-cell lung cancer. Ann Thorac Surg. 2007;83:419–24.PubMedCrossRef
Metadaten
Titel
Prognostic significance of telomerase activity and some tumor markers in non-small cell lung cancer
verfasst von
Maha Hashim
Magda Sayed
Nervana Samy
Salah Elshazly
Publikationsdatum
01.03.2011
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 1/2011
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9444-0

Weitere Artikel der Ausgabe 1/2011

Medical Oncology 1/2011 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.