The diagnostic and prognostic relevance of human telomerase reverse transcriptase mRNA expression detected in situ in patients with nonsmall cell lung carcinoma

Abstract

BACKGROUND The objectives of this study were to evaluate the diagnostic and prognostic relevance of human telomerase reverse transcriptase (hTERT) detected in situ in patients with nonsmall cell lung carcinoma (NSCLC) and to investigate the possible correlations between hTERT mRNA in NSCLC and the patients' clinicopathologic features, including survival. METHODS hTERT mRNA was detected by in situ hybridization in 146 samples from patients with NSCLC. The signal intensity of hTERT mRNA expression was evaluated by two independent observers. The expression level was defined subjectively as strong, moderate, or weak. RESULTS hTERT mRNA was detected mainly in the cytoplasm of tumor cells. It was detected in the cytoplasm of 100% of samples from patients with NSCLC but was not detected in normal lung tissue, except in activated lymphocytes. There was a significant correlation between hTERT mRNA expression and pathologic tumor status, pathologic disease stage (pStage), and Ki‐67 labeling index. There was no significant correlation between hTERT mRNA expression and age, gender, pathologic lymph node status (pN), histology, or tumor differentiation. The 5‐year survival rates for patients with strong and moderate hTERT mRNA expression levels were 46.9% and 77.9%, respectively; the difference was statistically significant (P = 0.0001). A multivariate analysis of survival using a stepwise procedure revealed that hTERT mRNA expression, pN status, pStage, and age were statistically significant prognostic factors (P = 0.0029, P = 0.0012, P = 0.0237, and P = 0.0496, respectively). CONCLUSIONS The findings suggested that hTERT mRNA expression may be useful for the diagnosis of NSCLC and also may be an independent prognostic factor for patients with NSCLC. Cancer 2003;98:1008–13. © 2003 American Cancer Society. DOI 10.1002/cncr.11611

Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small-cell lung cancer

“…Such an association has been reported in mISH (Kumaki et al, 2001;Wang et al, 2002;Fujita et al, 2003;Lantuejoul et al, 2004) and immunohistochemistry studies (Kumaki et al, 2001;Toomey et al, 2001;Lantuejoul et al, 2004). In contrast, the prognostic value of hTERT mRNA expression assayed by RT -qPCR has been inconsistent Hara et al, 2001;Marchetti et al, 2002;Wu et al, 2003;Hsu et al, 2004).…”

“…Activations of the hTERT or ALT pathways are obligate for senescence bypass and for neoplastic transformation of normal cells (Newbold, 2002). Telomerase activity and/or hTERT expression are increased in cancers and are prognostic factors in various cancer types (Harada et al, 1999;Bieche et al, 2000;Lee et al, 2001;Marchetti et al, 2002;Wang et al, 2002;Fujita et al, 2003;Krams et al, 2003;Ohali et al, 2003;Tchirkov et al, 2003;Lantuejoul et al, 2004). However, the clinical impact of hTERT expression or activity in non-small-cell lung cancer (NSCLC) remains controversial (Albanell et al, 1997;Taga et al, 1999;Hirashima et al, 2000;Komiya et al, 2000;Toomey et al, 2001;Marchetti et al, 2002;Wang et al, 2002;Fujita et al, 2003;Wu et al, 2003;Hsu et al, 2004;Lantuejoul et al, 2004).…”

Frequent T cell responses against immunogenic targets in lung cancer patients for targeted immunotherapy

“…Data have shown that it is overexpressed in lung cancer in up to 85% of lung cancer patients (36). Studies have also demonstrated that hTERT overexpression in lung cancer correlates with poor prognosis (37,38). Trials evaluating the immunological and clinical response of a peptide vaccination with the optimized peptide telomerase reverse transcriptase p572Y (TERT572Y) showed that CTL response was detected in 76.2% of 21 patients after first vaccination and in 90.9% of 11 patients after the sixth vaccination.…”

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

“…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). The possibility that the level of hTERT mRNA and telomerase activity, rather than detectability of these parameters could have a predictive value might be one of the reasons for these discordant findings.…”

“…In patients with surgically-treated early-stage lung cancer a correlation has been found between a poor prognosis and detection in tumour tissue of either elevated hTERT expression [by RT-PCR (19)(20)(21)(22), immunohistochemistry (23) or ISH (24,25)] or telomerase activity (26)(27)(28)(29). However, data on this topic are not consistent since other studies failed to reveal a correlation between hTERT expression and (diseasefree) survival (28,30,31).…”