Detection of Numerical Chromosomal Aberration in Squamous Cell Carcinoma of the Lung by In Situ Hybridization Using #17 Centromeric Probes

Lee, Sang Sook; Han, Seong Beom; Park, Soong Kook

Abstract

This study was carried out to understand the relationship between specific chromosome changes and their phenotypic consequences at the tissue level of human lung cancers. Then paraffin-embedded human lung squamous cell carcinoma samples were investigated for in evidence of genetic alterations, using chromosome 7 and 17-specific repetitive alpha-satellite DNA probes. In situ hybridization procedure with chromosome-specific DNA probes was optimized for use on formalin-fixed paraffin-embedded lung tissue sections. The chromosome index ranged from 1.10 to 1.88(median, 1.49) for chromosome 7 and 1.20 to 1.98(median, 1.69) for chromosome 17. Normal lymphocytes and stromal cells showed one or two chromosome signals per cell in most cases. All tumors showed three or more chromosome signals per cell with range of 16.0% to 80.6% of cancer cells(median, 50.9%) for chromosome 7 and 32.7% to 84.7%(median, 69.9%) for chromosome 17. The chromosome index did not correlate with the DNA content in most cases. Chromosomes 7 and 17 were either overrepresented or underrepresented when they were compared with corresponding DNA index determined by FCM. An increase in copy number, particularly of chromosome 7 was associated with a less favorable phenotype, including high nuclear grade. In addition, chromosome alterations were differentially expressed in the different areas of the same tissue section, correlating with histologic heterogeneity. These results suggest that chromosome polysomy can be reliably detected in tissue sections using in situ hybridization. There is a strong correlation between genotypic abnormalities and tumor phenotype in human lung cancer. This capability will prove to be an important tool for determining the underlying genetic basis for tumor development, tissue phenotype heterogeneity and progression by allowing genetic determination to be made on paraffin-embedded tissue sections where tumor histologic architecture is preserved.