Biological significance of tumor thickness. Theoretical considerations based on computer simulation

Maximum vertical tumor thickness is a highly significant prognostic criterion in cutaneous melanoma. To date, little is known about the problem, 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. In a set of 35,000 simulated tumors, the thickness of the resulting tumor was measured and the functional simulation settings contributing to tumor thickness were identified by statistical methods. It turned out that in this theoretical model of tumor growth, besides time, which is the most important factor, other factors contribute to tumor thickness. These are tumor cell motility, particularly when stimulated by stromal elements, a decreased rate of tumor cell loss, and pronounced proliferation associated 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 may help to clarify the relationship of vertical tumor thickness and poor clinical outcome in cutaneous melanomas.