Three-dimensional patterns of lung tumor growth: association with tumor heterogeneity

Most histological Classifications of lung tumors assess information derived from 2-dimensional surfaces. However, tumors grow in 3 dimensions in a variety of architectural patterns that possibly reflect the histological type or progresssion status of the tumor. A new mathematically derived variable (Rratio) is presented, that assesses the overall 3-dimensional shape of a tumor and classifies tumors based on their sphericality. Analysis and comparison of groups of spherical and nonspherical tumors from mouse inbred strains and recombinant congenic strains with a strict set of predetermined histological criteria shows that Rratio is significantly associated with tumor heterogeneity and that histological differences exist between the spherical and nonspherical tumors. These results suggest that Rratio may be a valuable tool for the characterization of tumors and can be used to explore qualitative differences in tumors derived from segregating crosses.