Clonality of combined tumors.

Abstract

Tumors with mixed morphologic patterns (combined tumors) are sometimes encountered, and questions often arise regarding the mechanism of molecular pathogenesis of each component and their relationships. To determine whether different components of combined tumors contain the same or different genetic alterations, thus providing evidence for their clonality. Six combined tumors with 2 components (in each case, both components showed epithelial differentiation morphologically) were studied by microdissecting tumor cells from each morphologic area followed by loss of heterozygosity analysis. In 1 of the cases studied, the different morphologic areas contained different patterns of genetic alterations. In the remaining 5 cases, the different morphologic areas harbored identical genetic changes in the chromosome regions studied. The latter group, interestingly, included a colonic tumor with an area of tubulovillous adenoma and an area of neuroendocrine carcinoma, and 2 lung tumors with squamous carcinoma and small cell carcinoma components. Our results suggest that in the majority of combined tumors, cells with different phenotypes share similar genotype and may arise from a single precursor cell. However, in a minority of these tumors, different areas may be derived from different precursor cells.