HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Molecular characterization of small peripheral lung tumors based on the analysis of fine needle aspirates

I. Zudaire1,2, M.D. Lozano3, M.F. Vazquez4, M.J. Pajares1,5, J. Agorreta1,5, R. Pio1,6, J.J. Zulueta7, D.F. Yankelevitz8, C.I. Henschke9 and L.M. Montuenga1,5

1Oncology Division, Center for Applied Medical Research, 3Departments of Pathology, and 7Neumology, Clínica Universitaria de Navarra and 2Departments of Genetics, 6Biochemistry and 5Histology and Pathology, Schools of Medicine and Sciences, University of Navarra, Pamplona, Spain, Departments of 4Pathology and 8Radiology, Weill Medical College of Cornell University, New York, USA.

Offprint requests to: Luis M. Montuenga, Área de Oncología, Centro para la Investigación Médica Aplicada, University of Navarra, Avenida Pío XII, 55, 31008 Pamplona, Spain. e-mail: lmontuenga@unav.es


Summary. The computed tomography (CT)-based early lung cancer diagnostic technologies allow the detection of very small stage I lung tumors. As part of these screening protocols any suspicious nodule has to be diagnosed morphologically, which requires CT-guided Fine Needle Aspiration, open biopsy or surgery. Fine Needle Aspiration (FNA) cytology is a well-recognised method for a rapid and accurate diagnosis of small lung tumors. Molecular analysis of the FNA specimens could complement cytology diagnosis by the characterization of the biological traits at the preoperative stage. In this study, we aimed to characterize the biological profile of 33 paraffin-embedded transthoracic FNA samples obtained from three groups of lung cancer patients: two groups of small early-detected lung adenocarcinomas (radiologically subsolid and solid nodules) and a third group of small metastatic adenocarcinomas. Genetic analysis was performed by fluorescence in situ hybridization using the four-color LAVysion probe. p53 and Ki-67 protein expression was also evaluated by immunocytochemistry. The samples showed gains for all targets analyzed; two cases had EGFR gene amplification and two cases had MYC amplification. There were no significant differences in the percentage of genetically malignant cells and the expression of Ki-67 among the three groups. However, p53 accumulation was significantly higher in the metastatic group compared to the subsolid early-detected group (P = 0.001). In conclusion, molecular analysis of FNA specimens may provide useful information at preoperative stages. In our series, a good prognostic profile in subsolid early detected adenocarcinomas is suggested. Histol Histopathol 23, 33-40 (2008)

Key words: Fine Needle Aspiration Cytology, Fluorescence in situ hybridization, Immuno-cytochemistry, Lung cancer screening