Catalytic Subunit of Human Telomerase Reverse Transcriptase Is an Independent Predictor of Survival in Patients Undergoing Curative Resection of Hepatic Colorectal Metastases: A Multicenter Analysis

Dômont, Julien; Pawlik, Timothy M.; Boige, Valérie; Rosé, Mathieu; Weber, Jean Christophe; Hoff, Paulo M.; Brown, Thomas; Zorzi, Daria; Morat, Luc; Pignon, Jean-Pierre; Rashid, Asif; Jaeck, Daniel; Sabatier, Laure; Élias, Dominique; Tursz, Thomas; Soria, Jean Charles; Vauthey, Jean Nicolas

doi:10.1200/jco.2005.06.944

Cited by 56 publications

(32 citation statements)

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“…However, we were not able to identify any amino-acid sequence similarity between the two proteins that could have the immunological properties of NCL-hTERT, and the question of this misrecognition remains non-elucidated. Nevertheless, the identification of nucleolin as the protein recognized by NCL-hTERT antibody should lead to an urgent re-evaluation of the results obtained with this antibody and that are already published (Brustmann, 2005;Dalerba et al, 2005;Domont et al, 2005;Dutu et al, 2005;Elkak et al, 2005;Falchetti et al, 2003;Fullen et al, 2005;Gulmann et al, 2005;Kraemer et al, 2003;Lantuejoul et al, 2005;Lantuejoul et al, 2004;Luzar et al, 2005a;Luzar et al, 2005b;Maes et al, 2005;Sabah et al, 2004;Sato et al, 2004;Smith et al, 2004;Uziel et al, 2005;Yan et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…The most salient points are herein reported. A new mouse monoclonal antibody (Novocastra, NCL-hTERT, clone 44F12) has been widely used, based on the assumption that this antibody correctly recognizes the protein peptide against which it has been claimed to be developed (Brustmann, 2005;Dalerba et al, 2005;Domont et al, 2005;Dutu et al, 2005;Elkak et al, 2005;Falchetti et al, 2003;Fullen et al, 2005;Gulmann et al, 2005a;Kraemer et al, 2003;Lantuejoul et al, 2005;Lantuejoul et al, 2004;Luzar et al, 2005a;Luzar et al, 2005b;Maes et al, 2005;Sabah et al, 2004;Sato et al, 2004;Smith et al, 2004;Uziel et al, 2005;Yan et al, 2004). Using this antibody, we confirmed on western blots, as previously shown, the labelling of a unique protein band in the 100 kDa area, which is generally thought consistent with the estimated molecular weight of telomerase of 127 kDa (Wick et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Immunodetection of human telomerase reverse-transcriptase (hTERT) re-appraised: nucleolin and telomerase cross paths

Dudognon

Nguyen

et al. 2006

Journal of Cell Science

112

111

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The involvement of telomerase in cellular immortalization and senescence has often been assessed by means of telomerase expression at the RNA level and quantification of telomerase activity by the telomeric repeat amplification protocol assay. However, these methods either neglected the existence of various telomerase splice variants, or ignored the nonconventional functions of telomerase independent of its ability to elongate and maintain telomere length. Immunodetection of telomerase is now being recognized as a necessary approach to precisely elucidate its roles in oncogenesis and senescence. A few antibodies directed against the catalytic subunit of the human telomerase (hTERT) are currently used but their specificity is not always demonstrated. A survey of the literature showed inconsistencies and led us to comparatively re-evaluate the most frequently used antibodies. Surprisingly, mass spectrometry, two-dimensional gel analysis and immunofluorescent experiments revealed that the most frequently used hTERT immunoprobe, a mouse monoclonal antibody that was claimed to be directed against an hTERT protein epitope, in fact recognizes nucleolin rather than telomerase. Our findings have interesting implications regarding the biology of nucleolin and telomerase in the context of pathophysiological investigations recently carried out.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunodetection of human telomerase reverse-transcriptase (hTERT) re-appraised: nucleolin and telomerase cross paths

Dudognon

Nguyen

et al. 2006

Journal of Cell Science

112

111

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“…Using a mouse monoclonal anti-hTERT antibody (clone 44F12, Novocastra), recent studies indicated that nucleolar expression of hTERT is associated with worse survival and is a better predictor than established clinical indicators in patients undergoing curative hepatic resection for colorectal metastases (31,32), whereas others showed that nucleolar hTERT expression is associated with better survival of patients with urothelial bladder cancer (33). However, this antibody (clone 44F12) has been shown to recognize nucleolin, but not hTERT (25).…”

Section: Discussionmentioning

confidence: 99%

High Levels of Nucleolar Expression of Nucleolin Are Associated with Better Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma

Peng

Liang

Wang

et al. 2010

Clinical Cancer Research

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Purpose: Nucleolin is a major nucleolar protein that has been shown to be overexpressed in rapidly dividing cells and plays an essential role in cell proliferation and survival. However, the expression and significance of nucleolin in pancreatic ductal adenocarcinoma (PDA) have not been studied.Experimental Design: We used a tissue microarray consisting of 1.0-mm cores of tumor and paired nonneoplastic pancreatic tissue from 69 pancreaticoduodenectomy specimens with stage II PDA. Nucleolin expression was evaluated by immunohistochemistry and scored quantitatively by image analysis. Nucleolin expression was classified as nucleolin-high or nucleolin-low using the median nucleolin labeling index of 3.5% as cutoff. Staining results were correlated with clinicopathologic features and survival.Results: Both PDAs and PDA cell lines showed nucleolar staining for nucleolin. Nucleolin expression was higher in PDAs and PDA cell lines than in nonneoplastic ductal epithelial cells. Among the 69 stage II PDAs, 34 (49%) were nucleolin-high. The median overall survival was 65.2 ± 16.3 months for patients who had nucleolin-high PDAs compared with 19.5 ± 3.3 months for patients whose tumors were nucleolin-low (P = 0.03, log-rank method). No significant correlation between nucleolin expression and other clinicopathologic parameters was found. In multivariate analysis, nucleolin expression was a prognostic factor for overall survival in patients with stage II PDA independent of patient's age, gender, tumor size, differentiation, and lymph node status.Conclusions: Nucleolin was overexpressed in PDAs and PDA cell lines. A high level of nucleolar expression of nucleolin was an independent prognostic marker for better survival for patients with stage II PDAs. Clin Cancer Res; 16(14); 3734-42. ©2010 AACR.Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer death in the United States (1). Only 15% to 20% of patients diagnosed with PDA are surgically resectable and most of the patients who undergo resection have stage II disease. The long-term survival rate of patients who have curative resection is approximately 20%, with a median survival of 18 to 24 months (1). Despite pancreaticoduodenectomy, the disease commonly recurs, with the most common sites of recurrence being the liver, lung, peritoneal cavity, and pancreatic surgery bed; the prognosis is poor (1).Previous studies have shown that multiple genes are frequently altered in PDAs, including the activation of the K-ras oncogene by point mutation (2) and inactivation of the tumor suppressor genes p16 (3), SMAD4/ DPC4 (4, 5), and p53 (6). More recently, it has been shown that telomere shortening occurs at the early stage during the development of PDA. Telomere shortening was detected in 91% of the pancreatic intraepithelial neoplasia 1A (PanIN 1A), the earliest putative precursor lesion for PDAs (7). Telomere length is maintained by the human telomerase complex, which is composed of human telomerase RNA (hTR or TERC), and telomeraseassociated protein 1 ...

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“…Telomerase activity has been reported as an independent predictor of survival of patients with varying malignancies, such as neuroblastoma (36,37), meningioma (38), breast cancer (39) and hepatic metastases of colon carcinoma (40). Studies on the potentially prognostic value of telomerase activity or hTERT expression in tumours of surgically treated lung cancer patients have, however, yielded conflicting results (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients: the European Early Lung Cancer Project

et al. 2010

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Catalytic Subunit of Human Telomerase Reverse Transcriptase Is an Independent Predictor of Survival in Patients Undergoing Curative Resection of Hepatic Colorectal Metastases: A Multicenter Analysis

Abstract: hTERT nucleolar expression is associated with worse survival after resection of hepatic CRM. hTERT expression in conjunction with number of hepatic metastases and disease-free interval may permit more accurate prediction of survival after resection of hepatic CRM.

Cited by 56 publications

References 45 publications

Immunodetection of human telomerase reverse-transcriptase (hTERT) re-appraised: nucleolin and telomerase cross paths

Immunodetection of human telomerase reverse-transcriptase (hTERT) re-appraised: nucleolin and telomerase cross paths

High Levels of Nucleolar Expression of Nucleolin Are Associated with Better Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma

Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients: the European Early Lung Cancer Project

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