BIOLOGICAL SIGNIFICANCE OF TUMOR THICKNESS - THEORETICAL CONSIDERATIONS BASED ON COMPUTER-SIMULATION

Maximum vertical tumor thickness is a highly significant prognostic cr iterion in cutaneous melanoma. To date, little is known about the prob lem, why thick lesions are more capable of metastatic spread than thin ones. To evaluate theoretical possibilities of the biological impact of thick lesions, computer simulation of tumor growth was performed. I n a set of 35,000 simulated tumors, the thickness of the resulting tum or was measured and the functional simulation settings contributing to tumor thickness were identified by statistical methods. It turned out were identified by statistical methods. It turned out that in this th eoretical model of tumor growth, besides time, which is the most impor tant factor, other factors contribute to tumor thickness. These are tu mor cell motility, particularly when stimulated by stromal elements, a decreased rate of tumor cell loss, and pronounced proliferation assoc iated with high numbers of cell cycle generations in the tumor cells. These findings are in agreement with experimental data indicating that metastatic capacity may depend on increased motility, stroma-induced motility stimulation, evasion from the host immune system, and genetic instability manifesting during cell cycling. Thus the observations ma y help to clarify the relationship of vertical tumor thickness and poo r clinical outcome in cutaneous melanomas.