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Eur J Cardiothorac Surg 2003;23:199-200
© 2003 Elsevier Science NL
a The Yorkshire Laser Centre, Goole and District Hospital, Woodland Avenue, Goole, East Yorkshire DN14 6RX, UK
b Postgraduate School of Medicine, The University of Hull, Hull, UK
Received 27 November 2002; accepted 27 November 2002.
* Corresponding author. Tel./fax: +44-1724-290456.
e-mail: kmoghissi{at}yorkshirelasercentre.org
Key Words: Telomerase • Lung cancer • Bronchial lavage
Detection of telomerase activity in bronchial lavage as an adjunct to cytological diagnosis in lung cancer
In the early years of the 20th century surgical resection, which was the standard form of treatment for most tumours, could not be applied to lung cancer due to the pneumothorax issue [1]. With this problem solved, surgical intervention became the treatment of choice at least since 1933 when the first pneumonectomy for cancer was performed [2]. One of the most significant advances in surgical therapy for lung cancer was the realisation in the 1950s that resectability did not equate with operability and that a selection process should operate in order, not only to reduce the number of thoracotomies which failed to offer successful resection but also to improve survival. This led to the establishment of oncologically based patient selection criteria for operation and monitoring of outcome and reliance on TNM classification. Progress in genetic and molecular biological research over the past 10–15 years is gradually shifting the emphasis from cyto/histopathological analysis to a more molecular based methodology for diagnosis and prognosis. It is now generally agreed that lung carcinogenesis is a multistep process and that genetic alternations precede morphological and cyto/histological changes. In recent years considerable effort has led to the discovery of a number of relevant proto-oncogenes, suppressor genes and DNA repair genes which are expressed aberrantly in lung cancer. The pressing issue is to establish the correlation between molecular genetic events and cyto/histological findings, which remain the gold standard of cancer diagnosis, and to identify biomarkers of cancer. An understanding of the genetic and molecular events will become increasingly important to the thoracic surgeon since, in the not-too-distant future, these are likely to be the tools of choice for detection of lung cancer in its early stages and for treatment monitoring and prognosis.
Currently, most research is directed towards study of the correlation between molecular events and histopathology and in identifying the markers which could signal genetic changes in the cell from normal to malignant prior to microscopic cyto/histological manifestations. It is in this context that the study by Dikmen and colleagues [3], on detection of telomerase activity in bronchial lavage of lung cancer patients compared with those with benign lung disease, is of interest. The number of patients in the series is small and, therefore, it is difficult to draw decisive conclusions despite the rather strong statement by the authors that "assay of telomerase activity in bronchial lavage fluid is highly sensitive in the detection of lung cancer". Dr Dikmen and colleagues’ study concerns 29 patients: 22 with malignant lung tumours and seven with benign disease. The aim was to outline the value of telomerase activity for detection of malignancy in bronchial lavage samples and to compare the results with that of cytology examination.
The rationale of the authors in comparing telomerase activity in malignant and benign disease is understandable, although the use of histologically normal tissue also would have been ideal. The fact that telomerase activity was observed in one case where the patient had only a lung abscess would support the use of normal control tissue. There are a few points emerging from this study which we believe to be important and could be relevant to cancer detection in conjunction with fluorescence bronchoscopy. We note that telomerase activity was recorded in all 13 patients whose cancers were visible at bronchoscopy. Ten of 12 patients with squamous cell cancer were telomerase-positive whereas only four out of eight patients with adenocarcinoma showed activity. These observations could suggest that telomerase activity as a marker is more likely to be of help in those cancers that arise in bronchial mucosa (central tumours) rather than in the periphery of the lung. The authors have not stated how many of these eight tumours were visible at bronchoscopy, but we assume from Table 1 that they would mostly have been peripheral tumours.
From the above observations one may postulate that telomerase could be a good tumour marker in bronchogenic squamous cell carcinoma, probably central as opposed to peripheral. This seems to accord with the preliminary results of a study that is in progress at the Yorkshire Laser Centre [4]. In this study high-risk volunteers are screened by white and fluorescence bronchoscopy; brush/biopsy sampling of bronchial mucosa; cyto/histology examination; and for telomerase activity. In our initial evaluation there was substantially higher activity in patients with abnormal fluorescence image of the mucosa than in those with a normal image. Clearly, therefore, larger definitive studies are needed to validate the promising results for the use of telomerase activity as a marker of tumour detection.
Overall, the results reported here are consistent with previous studies, cited by Dikmen and colleagues, demonstrating that telomerase may have a useful role in the early diagnosis of lung cancer, as well as other tumours: a topic recently reviewed by Hiyama and Hiyama [5]. Reports on the clinical utility of telomerase are appearing more often in the literature, e.g. a recent study by Wang et al. [6] reported hTERT expression being associated with shorter overall survival, shorter disease-specific survival and shorter disease-free survival in stage I non-small cell lung cancer. In this study the independent prognostic value of TERT expression was confirmed in multivariate analysis.
Finally, as interesting as this study by Dr. Dikmen and colleagues is, it cannot support the conclusion that "assay of telomerase activity in bronchial lavage fluid is highly sensitive in the detection of early lung cancer" when telomerase measurements alone are used for diagnostic purposes, without the support of other genetic testing or fluorescence bronchoscopy. More evidence is needed before such a conclusion is justifiable, although it may not be too long before this is presented.
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