Quantitative fluorescence in situ hybridization in lung cancer as a diagnostic marker

The diagnosis of lung cancer is quite often hampered by the existence of va rious cell types within samples such as biopsies or pleural effusions. We h ave established a new marker for image cytometry of interphase tumor cells of the lung by using the most recurrent and early cytogenetic event in lung cancer, the loss of the short arm of chromosome 3. The method is based on the detection of the imbalance between the long and the short arms of chrom osome 3 by performing two-color fluorescence in situ hybridization on both arms. Fourteen tumors were analyzed after short-term culture and compared w ith the corresponding cytogenetic data obtained from metaphase analysis. Re sults on interphase nuclei and control experiments on metaphases were the s ame, with imbalance ratios ranging from 1.0 to 2.0 (mean value 1.6, median 1.5). To assess the clinical significance of this approach, three pleural e ffusions were analyzed. Data showed that normal cells within the sample cou ld have been distinguished from the tumor cells based on different imbalanc e values between the long and the short arms. Thus, our method allows refin ed detection of lung tumor cells within samples containing heterogeneous ce ll populations.