Prognostic value of human telomerase reverse transcriptase gene expression in oral carcinogenesis.

Department of Surgical Sciences, University of Foggia, Foggia, Italy.
International Journal of Oncology (Impact Factor: 3.03). 07/2007; 30(6):1349-57. DOI: 10.3892/ijo.30.6.1349
Source: PubMed

ABSTRACT Human telomerase reverse transcriptase (hTERT) gene expression in resected specimens of oral squamous cell carcinoma (OSCC) and their surrounding tissue, either apparently normal or clearly histologically dysplastic, was evaluated by both real-time RT-PCR and immunohisto-chemical protein analyses. The expression level of hTERT in oral dysplasia and in OSCC was markedly higher than in normal tissues. The correlation between hTERT expression in OSCC and clinico-pathological parameters or survival of OSCC patients was statistically analyzed. Our study demonstrates that there is no significant relationship between hTERT expression and classical clinico-pathological parameters. Interestingly, survival analysis showed both overexpressing cases and lower survival rate in the early stage of OSCC (p=0.03 for immunohistochemistry; p=0.04 for RT real-time PCR). The histological location of hTERT in these tumors has been discussed in the context of the cancer stem cell theory.

Download full-text


Available from: Salvatore de maria, Aug 18, 2015
  • Source
    • "and/or abnormal expression of CDK4/cyclinD1 [18] [20] [36] [37]. OSCCs, like many other carcinomas , maintain telomere length with telomerase activation [21] [22]. Immortality is one of the important characteristics of malignancy and ectopic expression of these genes thus could mimic the events that occur during development of OSCCs. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Oral squamous cell carcinomas (OSCCs) are considered to arise from human oral keratinocytes. DNAs of human papillomaviruses (HPVs), predominantly types 16 and 18, etiological agents of cervical cancer, have been detected in approximately 25% of OSCCs. In accordance with the established role of E6 and E7 in inactivating p53 and pRB, respectively, mutations of p53 and inactivation of p16(INK4a) are frequently observed in HPV-negative OSCCs. In addition, other alterations such as overexpression of epidermal growth factor receptor (EGFR) are often observed in both HPV-positive and -negative OSCCs. However, causal-relationships between accumulation of these abnormalities and multi-step carcinogenesis are not fully understood. To elucidate underlying processes, we transduced either HPV16 E6/E7 or mutant CDK4 (CDK4(R24C)), cyclin D1 and human telomerase reverse transcriptase (TERT) into primary human tongue keratinocytes (HTK), and obtained immortal cell populations, HTK-16E6E7 and HTK-K4DT. Additional transduction of oncogenic HRAS or EGFR together with MYC into the HTK-16E6E7 and dominant-negative p53 expressing HTK-K4DT resulted in anchorage-independent growth and subcutaneous tumor formation in nude mice. These results indicate that either HRAS mutation or activation of EGFR in cooperation with MYC overexpression play critical roles in transformation of HTKs on a background of inactivation of the pRB and p53 pathways and telomerase activation. This in vitro model system recapitulating the development of OSCCs should facilitate further studies of mechanisms of carcinogenesis in the oral cavity.
    American Journal of Cancer Research 01/2011; 1(7):869-81. · 3.97 Impact Factor
  • Source
    • "Previous reference to hTERT activity in head and neck cancer has been with respect to OSCC and related mucosal dysplasia. In particular, using RT – PCR expression analysis, Pannone et al (2007) found 66% of OSCC tumours to be overexpressing hTERT by comparison with normal tissues. The hTERT promoter hypermethylation has been implicated in cervical cancer progression while not correlating with down-regulation hTERT expression (Widschwendter et al, 2004; Iliopoulos et al, 2009; Kumari et al, 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: potential epigenetic biomarkers for malignant transformation to carcinoma ex pleomorphic adenoma (Ca ex PSA) have been sought previously with and without specific comparison with the benign variant, pleomorphic salivary adenoma (PSA). Previous analysis has been limited by a non-quantitative approach. We sought to demonstrate quantitative promoter methylation across a panel of tumour suppressor genes (TSGs) in both Ca ex PSA and PSA. quantitative methylation-specific real-time polymerase chain reaction (qMSP) analysis of p16(INK4A), CYGB, RASSF1, RARβ, human telomerase reverse transcriptase (hTERT), Wilms' tumour 1 (WT1) and TMEFF2 gene promoters was undertaken on bisulphite-converted DNA, previously extracted from archival fixed tissue specimens of 31 Ca ex PSA and an unrelated cohort of 28 PSA. All target regions examined had formerly been shown to be hypermethylated in salivary and/or mucosal head and neck malignancies. the qMSP demonstrated abnormal methylation of at least one target in 20 out of 31 (64.5%) Ca ex PSA and 2 out of 28 (7.1%) PSA samples (P<0.001). RASSF1 was the single gene promoter for which methylation is shown to be a statistically significant predictor of malignant disease (P<0.001) with a sensitivity of 51.6% and a specificity of 92.9%. RARβ, TMEFF2 and CYGB displayed no apparent methylation, while a combinatory epigenotype based on p16, hTERT, RASSF1 and WT1 was associated with a significantly higher chance of detecting malignancy in any positive sample (odds ratio: 24, 95% CI: 4.7-125, P<0.001). we demonstrate the successful application of qMSP to a large series of historical Ca ex PSA samples and report on a panel of TSGs with significant differences in their methylation profiles between benign and malignant variants of pleomorphic salivary adenoma. qMSP analysis could be developed as a useful clinical tool to differentiate between Ca ex PSA and its benign precursor.
    British Journal of Cancer 11/2010; 103(12):1846-51. DOI:10.1038/sj.bjc.6605953 · 4.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study aimed to look at whether a correlation exists between telomerase activity and survival of laryngeal carcinoma patients. Telomerase activity was measured by telomerase repeat amplification protocol in 31 laryngeal carcinomas and adjacent normal tissues, and in 21 vocal cord polyps (controls). Follow-up was for at least 60 months. Telomerase activity in tissues adjacent to laryngeal carcinomas was significantly higher than in the carcinomas which was, in turn, significantly higher than in vocal cord polyps. There was no significant difference between telomerase activity in carcinomas or adjacent tissues and clinicopathological characteristics. Patients with high telomerase activity in carcinoma tissue had significantly shorter survival times than those with low activity, but no significance difference was observed between survival time and telomerase status in adjacent tissues. Linear regression showed significant association between telomerase activity levels in carcinoma tissues and survival time, but this was not observed in adjacent tissues. This study suggests that telomerase activation probably takes place before the cancer phenotype develops and has prognostic significance for survival of patients with laryngeal carcinoma.
    The Journal of international medical research 03/2008; 36(2):336-42. DOI:10.1177/147323000803600217 · 1.10 Impact Factor
Show more