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A fluorescence in situ hybridization-based assay for improved detection of lung cancer cells in bronchial washing specimens.

Sokolova IA,Bubendorf L,O'Hare A,Legator MS,Jacobson KK,Grilli B S B,Dalquen P,Halling KC,Tamm M,Seelig SA,Morrison LE

Abstract

Interphase fluorescence in situ hybridization (FISH) is a powerful tool for detecting chromosome and locus-specific changes in tumor cells. We developed a FISH-based assay to detect genetic changes in bronchial washing specimens of lung carcinoma patients.
The assay uses a mixture of fluorescently labeled probes to the centromeric region of chromosome 1 and to the 5p15, 8q24 (site of the c-myc gene), and 7p12 (site of the EGFR gene) loci to assess cells in bronchial washing specimens for chromosomal abnormalities indicative of lung carcinoma. The FISH assay was performed on 74 specimens that had been assessed previously for evidence of malignancy by routine cytology with Pap staining.
Forty-eight patients had histologically confirmed lung carcinoma and 26 patients had a clinical diagnosis that was negative for lung carcinoma. FISH analysis was performed without knowledge of the patient's clinical information. The finding of six or more epithelial cells with gains of two or more chromosome regions was considered a positive FISH result (i.e., evidence of malignancy). The sensitivity of FISH for the detection of lung carcinoma was 82% in this set of specimens compared with a 54% sensitivity by design for cytology (FISH vs. cytology, P = 0.007). FISH detected 15 of 18 specimens that were falsely negative by cytology. The specificities of FISH and cytology were 82% and 100%, respectively, and were not significantly different (P = 0.993).
The data indicate a potential utility of the FISH assay as an adjunct to bronchial washing cytology in routine clinical practice.

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