Published ahead of print on November 7, 2007, doi:10.1164/rccm.200708-1142OC Am. J. Respir. Crit. Care Med., Volume 177, Number 3, February 2008, 342-347 A more recent version of this article appeared on February 1, 2008
Submitted on August 1, 2007 Chromosomal Aneusomy in Bronchial High Grade Lesions is Associated with Invasive Lung CancerSteinn Jonsson1,1 Department of Medicine, University of Colorado Health Sciences Center, Pulmonary Division, Aurora, CO, USA; Department of Medicine, University of Iceland Hospitals, Reykjavik, Iceland, 2 Department of Medicine, University of Colorado Health Sciences Center, Pulmonary Division, Aurora, CO, USA, 3 Department of Medicine, University of Colorado Health Sciences Center, Pulmonary Division, Aurora, CO, USA; Pulmonary Division, Department of Medicine, Denver Veterans Affairs Medical Center, Denver, CO, USA, 4 Preventive Medicine and Biostatistics, University of Colorado Health Sciences Center, Pulmonary Division, Aurora, CO, USA, 5 Department of Medicine, Presbyterian/St. Lukes Health One Medical Center, Denver, CO, USA, 6 Department of Pathology, University of Iceland Hospitals, Reykjavik, Iceland, 7 Department of Respiratory Medicine, British Columbia Cancer Agency, Vancouver, Canada, 8 Department of Pathology, University of Colorado Health Sciences Center, Pulmonary Division, Aurora, CO, USA * To whom correspondence should be addressed. E-mail: marileila.garcia{at}uchsc.edu.
Rationale: The development of lung cancer (LC) is accompanied by field changes in the airway mucosa that may have prognostic importance. Objective: To compare patients with prevalent lung cancer to controls regarding their histological dysplasia scores and chromosomal aneusomy as measured by fluorescence in situ hybridization (FISH). Methods: The most advanced bronchial histology lesion was assessed from 44 lung cancer cases and 90 cancer free controls using a 4-color FISH probe set encompassing the chromosome 6 centromere, 5p15.2, 7p12 (EGFR), and 8q24 (MYC) sequences. Histology grades were coded as dysplasia (moderate or severe) or carcinoma in situ (CIS). Results: CIS was the highest histologic grade for 32 subjects, and dysplasia was the highest grade for 102 subjects (54 moderate, 48 severe). Chromosomal aneusomy was seen in 64% of the LC cases but in only 31% of the controls (OR=4.68, 95% CI 1.97-11.04). Among those with any level of dysplasia the odds ratio for positive FISH and lung cancer was 2.28 (95% CI 0.75 to 6.86). Among those with CIS the odds ratio for positive FISH and lung cancer was 5.84 (95% CI 1.31 to 26.01). Conclusions: Chromosomal aneusomy is associated with lung cancer. Prospective examination of aneusomy as a precursor lesion that predicts lung cancer is needed. Key words: Chromosomal aneusomy, FISH, Carcinoma in situ, Premalignancy
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