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The Use of Genetic Markers to Identify Lung Cancer in Fine Needle Aspiration Samples

Purpose: We seek to establish a genetic test to identify lung cancer using cells obtained through computed tomography–guided fine needle aspiration (FNA). Experimental Design: We selected regions of frequent copy number gains in chromosomes 1q32, 3q26, 5p15, and 8q24 in non–small cell lung cancer and tested their ability to determine the neoplastic state of cells obtained by FNA using fluorescent in situ hybridization. Two sets of samples were included. The pilot set included six paraffin-embedded, noncancerous lung tissues and 33 formalin-fixed FNA specimens. These 39 samples were used to establish the optimal fixation and single scoring criteria for the samples. The test set included 40 FNA samples. The results of the genetic test were compared with the cytology, pathology, and clinical follow-up for each case to assess the sensitivity and specificity of the genetic test. Results: Nontumor lung tissues had ≤4 signals per nucleus for all tested markers, whereas tumor samples had ≥5 signals per nucleus in five or more cells for at least one marker. Among the 40 testing cases, 36 of 40 (90%) FNA samples were analyzable. Genetic analysis identified 15 cases as tumor and 21 cases as nontumor. Clinical and pathologic diagnoses confirmed the genetic test in 15 of 16 lung cancer cases regardless of tumor subtype, stage, or size and in 20 of 20 cases diagnosed as benign lung diseases. Conclusions: A set of only four genetic markers can distinguish the neoplastic state of lung lesion using small samples obtained through computed tomography–guided FNA.