COMPUTER-SIMULATIONS OF HISTOLOGIC PATTERNS IN MELANOMA USING A CELLULAR-AUTOMATON PROVIDE CORRELATIONS WITH PROGNOSIS

Computer simulations have been used frequently in the life sciences to investigate the mechanisms of morphologic pattern formation, The cell ular automaton program SMN5 is designed to simulate tumor growth and t o estimate biologic properties by comparing real tumor patterns with c omputer-simulated reference patterns, This method was applied to 195 c ases of primary melanoma of the skin, S-100-stained sections were eval uated by image analysis and compared statistically to a reference set of 4000 simulated patterns, Estimates of tumor cell proliferation, mot ility, cell loss, cohesion, stroma destruction, and intercellular sign als (autocrine and paracrine factors affecting growth, motility, and c ell loss) were calculated, Twelve of 18 estimated parameters correlate d significantly with tumor progression, as indicated by vertical tumor thickness (linear regression analysis: p less than or equal to 0.05), and 13 of 18 parameters carried prognostic significance (log rank tes t: p less than or equal to 0.05). Poor prognosis was associated partic ularly with a pronounced increase in the estimates of proliferation, t umor cell motility, and stromal degradation, Poor prognosis was also a ssociated with a decrease in the estimates of cell loss, tumor cell co hesion, and paracrine growth factor dependence, In multivariate analys is using Cox's proportional hazard model, stromal degradation and moti lity showed prognostic information in addition to conventional prognos tic parameters, The study shows that analytical comparison of real tum ors with computer-simulated patterns of a cellular automaton facilitat es a functional interpretation of tumor morphology, which carries prog nostic significance in cutaneous melanoma.