Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Νικόλαος Κουλούρης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Συρίγος, Καθηγητής, Ιατρικής Σχολή, ΕΚΠΑ
Πέτρος Μπακάκος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Νικόλαος Τζανάκης, Καθηγητής, Ιατρικής Σχολή, Πανεπιστήμιο Κρήτης
Πασχάλης Στειρόπουλος, Αναπληρωτής Καθηγητής, Τμήμα Ιατρικής, Δημοκρίτειο Πανεπιστήμιο Θράκης
Ηλίας Κοττέας, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Νικολέττα Ροβίνα, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Συμβολή στη διερεύνηση κλινικών και παθογενετικών χαρακτηριστικών ασθενών με διάμεσες πνευμονοπάθειες και καρκίνο πνεύμονα
Translated title:
Clinical and pathogenic characteristics of patients with interstitial lung disease and lung cancer
Summary:
Background: Interstitial lung diseases (ILD), mainly idiopathic pulmonary fibrosis (IPF) are frequently complicated with lung cancer. Lung tumors in patients with IPF are mainly squamous carcinomas, in the periphery of the lungs and in proximity with fibrotic lesions. The pathogenetic mechanisms of lung cancer development within the fibrotic lungs remain elusive. Human telomerase reverse transcriptase (hTERT) is the catalytic subunit and the rate-limiting component of telomerase enzyme, which adds nucleotides to telomeres and counteracts their length shortening. The development of a telomere maintenance mechanism represents a hallmark of cancer, either by reactivating telomerase in order to maintain telomeres and avoid senescence or by other recombination-based pathways, known as the alternative lengthening of telomeres, occurring mostly in mesenchymal tumors. On the other hand, IPF is associated with mutations in telomerase genes and shorter telomeres. The telomere maintenance mechanisms in patients with lung cancer and IPF have not been studied.
Aim: To investigate the expression of hTERT in lung cancer with co-existing IPF, to compare with lung cancer without fibrosis and to correlated with clinicopathological data.
Methods: Diagnostic lung cancerous biopsies were retrieved from 18 patients with lung cancer and concomitant IPF, as well as 18 age and gender matched controls with lung cancer without pulmonary fibrosis. The expression of hTERT was studied with immunohistochemistry. ImajeJ software was used to quantitate subcellular stain intensity. Immunohistochemical investigation of two senescence-associated markers, p16INK4A and p21WAF1/CIP1, was also performed in all 36 cases.
Results: Both groups highly expressed hTERT, without significant difference (100% vs 95%, p=0.521). The percentage of hTERT-positive cancer cells did not correlated with any baseline clinicopathologic characteristic. Evaluation of p16 and p21 immunostaining revealed negative to minimal immunoreactivity in both groups. The localization of hTERT stain exhibited higher median nuclear intensity in the group of lung cancer with IPF (0.62 vs 0.45, p=0.016), while cytoplasmic intensity did not differ significantly (0.17 vs 0.15, p=0.463). Higher median nuclear intensity was also correlated with small cell lung cancer subtype in the whole study sample (0.69 vs 0.45, p=0.09).
Conclusion: hTERT is highly expressed in lung cancer with concomitant IPF, but with differential localization compared to lung cancer without IPF. Higher nuclear intensity of hTERT was also observed in samples of SCLC compared to NSCLC. The differential localization implies differences in pathogenicity and requires further investigation.
Main subject category:
Health Sciences
Keywords:
Interstitial lung disease, Idiopathic Pulmonary Fibrosis, Lung Cancer, Telomeres, Telomerase
Number of references:
235
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Gomatou_Georgia_PhD.pdf
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