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Chromosomal Aneusomy in Bronchial High-Grade Lesions Is Associated with Invasive Lung Cancer

¹ Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado; ² Department of Medicine, University of Iceland Hospitals, Reykjavik, Iceland; ³ Pulmonary Division, Department of Medicine, Denver Veterans Affairs Medical Center, Denver, Colorado; ⁴ Department of Preventive Medicine and Biostatistics, University of Colorado Health Sciences Center, Denver, Colorado; ⁵ Pulmonary Division, Department of Medicine, Presbyterian/St. Luke's Health One Medical Center, Denver, Colorado; ⁶ Department of Pathology, University of Iceland Hospitals, Reykjavik, Iceland; ⁷ Department of Respiratory Medicine, British Columbia Cancer Agency, Vancouver, Canada; and ⁸ Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to Marileila Varella-Garcia, Ph.D., Department of Medicine/Medical Oncology, University of Colorado Health Sciences Center, Campus Box 6511, Mail Box 8117, Aurora, CO 80045. 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.

Objectives: To compare patients with prevalent LC to control subjects regarding their histologic dysplasia scores and chromosomal aneusomy as measured by fluorescence in situ hybridization (FISH).

Methods: The most advanced bronchial histology lesion was assessed from each of 44 LC cases and 90 cancer-free control subjects using a four-color FISH probe set encompassing the chromosome 6 centromere, 5p15.2, 7p12 (epidermal growth factor receptor), and 8q24 v-myc myelocytomatosis viral oncogene homolog (MYC) sequences. Histology grades were coded as dysplasia (moderate or severe) or carcinoma in situ (CIS).

Measurements and Main 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 control subjects (odds ratio [OR], 4.68; 95% confidence interval [CI]. 1.97–11.04). Among those with any level of dysplasia, the OR for positive FISH and LC was 2.28 (95% CI, 0.75–6.86). Among those with CIS, the OR for positive FISH and LC was 5.84 (95% CI, 1.31–26.01).

Conclusions: Chromosomal aneusomy is associated with LC. Prospective examination of aneusomy as a precursor lesion that predicts LC is needed.

Key Words: chromosomal aneusomy • fluorescence in situ hybridization • carcinoma in situ • premalignancy

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Lung cancer (LC) develops through accumulation of multiple molecular and genetic changes, but the association between chromosomal aneusomy in bronchial lesions and LC risk is not well studied. What This Study Adds to the Field Carcinoma in situ and chromosomal aneusomy were identified as predictors of invasive LC in a case-control study of high-risk subjects. The interaction of these markers may improve the diagnostic capability in preneoplastic bronchial lesions.