title: Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients: the European Early Lung Cancer Project.
abstract: Lung cancer is the most important cause of cancer-related mortality. Resectability and eligibility for treatment with adjuvant chemotherapy is determined by staging according to the TNM classification. Other determinants of tumour behaviour that predict disease outcome, such as molecular markers, may improve decision-making. Activation of the gene encoding human telomerase reverse transcriptase (hTERT) is implicated in the pathogenesis of lung cancer, and consequently detection of hTERT mRNA might have prognostic value for patients with early stage lung cancer. A cohort of patients who underwent a complete resection for early stage lung cancer was recruited as part of the European Early Lung Cancer (EUELC) project. In 166 patients expression of hTERT mRNA was determined in tumour tissue by quantitative real-time RT-PCR and related to that of a house-keeping gene (PBGD). Of a subgroup of 130 patients tumour-distant normal tissue was additionally available for hTERT mRNA analysis. The correlation between hTERT levels of surgical samples and disease-free survival was determined using a Fine and Gray hazard model. Although hTERT mRNA positivity in tumour tissue was significantly associated with clinical stage (Fisher's exact test p=0.016), neither hTERT mRNA detectability nor hTERT mRNA levels in tumour tissue were associated with clinical outcome. Conversely, hTERT positivity in adjacent normal samples was associated with progressive disease, 28% of patients with progressive disease versus 7.5% of disease-free patients had detectable hTERT mRNA in normal tissue [adjusted HR: 3.60 (1.64-7.94), p=0.0015]. hTERT mRNA level in tumour tissue has no prognostic value for patients with early stage lung cancer. However, detection of hTERT mRNA expression in tumour-distant normal lung tissue may indicate an increased risk of progressive disease.
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, 1081 HV Amsterdam, The Netherlands.
authors.forename: Remco M
authors.initials: RM
authors.lastname: Van den Berg
authors.forename: Hes
authors.initials: H
authors.lastname: Brokx
authors.forename: Aurélien
authors.initials: A
authors.lastname: Vesin
authors.forename: John K
authors.initials: JK
authors.lastname: Field
authors.forename: Christian
authors.initials: C
authors.lastname: Brambilla
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: G Thomas
authors.initials: GT
authors.lastname: Sutedja
authors.forename: Daniëlle A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: Pieter E
authors.initials: PE
authors.lastname: Postmus
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
mesh_terms: D000368:Aged; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D055088:Early Detection of Cancer; D005060:Europe; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D013048:Specimen Handling; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase