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6th ESACP Congress, Heidelberg, April 7-11, 1999 |
A069
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.
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