Chromosomal aneusomy in bronchial high-grade lesions is associated with invasive lung cancer

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.