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JMD 1999, Vol. 1, No. 1
Copyright © 1999 American Society for Investigative Pathology & Association for Molecular Pathology

Quantitative Fluorescence in Situ Hybridization in Lung Cancer as a Diagnostic Marker

Khuong Truong^*, Michèle Gerbault-Seureau^*, Marie-Noëlle Guilly, Philippe Vielh, Gérard Zalcman^§, Alain Livartowski, Alain Chapelier^¶, Marie-France Poupon^*, Bernard Dutrillaux^* and Bernard Malfoy^*

From the Cytogénétique Moléculaire et Oncologie, * Unité Mixte de Recherche 147, Centre National de Recherche Scientifique, Institut Curie, Paris; the Département de Radiobiologie et Radiopathologie-Direction de Sciences du Vivant, Commissariat à l’Energie Atomique, Fontenay-Aux-Roses; the Cytopathologie et Cytométrie Clinique, Laboratoire de Recherche Correspondant, Commissariat à l’Energie Atomique # 14, Institut Curie, Paris; the Département d’Oncologie Médicale, ^§ Institut Curie, Paris; and the Hôpital Marie Lannelongue, ^¶ Le Plessis-Robinson, France

The diagnosis of lung cancer is quite often hampered by the existence of various cell types within samples such as biopsies or pleural effusions. We have 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 chromosome 3 by performing two-color fluorescence in situ hybridization on both arms. Fourteen tumors were analyzed after short-term culture and compared with the corresponding cytogenetic data obtained from metaphase analysis. Results on interphase nuclei and control experiments on metaphases were the same, 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 effusions were analyzed. Data showed that normal cells within the sample could have been distinguished from the tumor cells based on different imbalance values between the long and the short arms. Thus, our method allows refined detection of lung tumor cells within samples containing heterogeneous cell populations.