DNA Copy Number Alterations in Endobronchial Squamous Metaplastic Lesions Predict Lung Cancer
| Autor: | Petrus Josephus Ferdinandus Snijders, M.A. van de Wiel, C. J. L. M. Meijer, Katrien Grünberg, E. Reinen, Clarissa Kooi, Gerrit A. Meijer, Daniëlle A.M. Heideman, Bauke Ylstra, Johannes M.A. Daniels, R.A.A. van Boerdonk, Frederik B. Thunnissen, Egbert F. Smit, Saskia M. Wilting, Pieter E. Postmus, T. G. Sutedja, Sylvia Duin |
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| Přispěvatelé: | Pathology, Pulmonary medicine, Epidemiology and Data Science, CCA - Oncogenesis |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Genetic Markers
Male Risk Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Lung Neoplasms DNA Copy Number Variations Biopsy Critical Care and Intensive Care Medicine Cohort Studies Bronchoscopy medicine Carcinoma Humans Lung cancer Aged Metaplasia medicine.diagnostic_test business.industry Carcinoma in situ Editorials Cancer Middle Aged medicine.disease Case-Control Studies Carcinoma Squamous Cell Biomarker (medicine) Female business Carcinoma in Situ Immunostaining Comparative genomic hybridization |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine, 184, 948-956. American Thoracic Society van Boerdonk, R A A, Sutedja, T G, Snijders, P J F, Reinen, E, Wilting, S M, van de Wiel, M, Thunnissen, F B J M, Duin, S, Kooi, C, Ylstra, B, Meijer, C J L M, Meijer, G A, Grünberg, K, Daniels, J M A, Postmus, P E, Smit, E F & Heideman, D A M 2011, ' DNA Copy Number Alterations in Endobronchial Squamous Metaplastic Lesions Predict Lung Cancer ', American Journal of Respiratory and Critical Care Medicine, vol. 184, pp. 948-956 . https://doi.org/10.1164/rccm.201102-0218OC |
| ISSN: | 1073-449X |
| DOI: | 10.1164/rccm.201102-0218OC |
| Popis: | Autofluorescence bronchoscopy (AFB) is a valid strategy for detecting premalignant endobronchial lesions. However, no biomarker can reliably predict lung cancer risk of subjects with AFB-visualized premalignant lesions.The present study set out to identify AFB-visualized squamous metaplastic (SqM) lesions with malignant potential by DNA copy number profiling.Regular AFB examinations in 474 subjects at risk of lung cancer identified six subjects with SqM lesions at baseline, and carcinoma in situ or carcinoma (carcinoma in situ or greater) at the initial SqM site at follow-up bronchoscopy. These progressive SqM lesions were compared for immunostaining pattern and array comparative genomic hybridization-based chromosomal profiles with 23 SqM lesions of subjects who remained cancer-free. Specific DNA copy number alterations (CNAs) linked to cancer risk were identified and accuracy of CNAs to predict endobronchial cancer in this series was determined.At baseline, p53, p63, and Ki-67 immunostaining were not predictive for a differential clinical outcome of SqM lesions. The mean number of CNAs in baseline SqM of cases was significantly higher compared with control subjects (P0.01). Chromosomal regions significantly more frequently altered in SqM of cases were 3p26.3-p11.1, 3q26.2-q29, 9p13.3-p13.2, and 17p13.3-p11.2 (family-wise error rate0.10). CNAs were specifically detected at the site of future cancer. In cases, baseline-detected CNAs persisted in subsequent biopsies taken from the initial site, and levels increased toward cancer progression. In this series, a model based on CNAs at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3 predicted cancer with 97% accuracy.The data suggest that the presence of specific CNAs in SqM lesions predict endobronchial cancer. |
| Databáze: | OpenAIRE |
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