6th ESACP Congress, Heidelberg, April 7-11, 1999

A069
CONTINUOUS PROGRESSION OF DIPLOID TUMOR CELLS IN ANEUPLOID HEAD AND NECK CARCINOMAS
Hemmer J, Polackova J, Kraft K

Division of Tumor Biology, University of Ulm, Germany

The development of aneuploid clones from diploid progenitor cells is an integral part of the pathogenesis of head and neck squamous cell carcinoma. Aneuploidy formation plays an essential role in the acquisition of invasive and metastatic growth patterns. Research interests have therefore largely been focused on cells with highly aberrant karyotypes. Virtually nothing is known about the fate and the potential tumor biological importance of diploid progenitor cell populations after the emergence of aneuploid clones. Using multivariate cytokeratin/DNA flow cytometry, we have shown that diploid tumor cells regularly persist after aneuploid cells have developed. Moreover, diploid tumor cells continue to proliferate, and they frequently represent the dominant malignant cell population in aneuploid primary carcinomas. FISH with centromeric and telomeric DNA probes indicates that DNA-diploid malignant cells mostly bear normal chromosome numbers, but may occasional show structural rearrangements. Despite the progression in primary aneuploid tumors, diploid tumor cells are always lacking in corresponding metastases. These results add further evidence of a largely reduced competence of diploid tumor cells to metastasize, but suggest a significant role in local tumor progression. Investigating the functional importance of tumor heterogeneity may thus increase our conceptional understanding of malignancy progression and may contribute to improve strategies for therapeutic targeting.