Figure 1.

IHC stains of two regions from a clinical invasive ductal breast cancer. The Ki67 stain identifies cells that are proliferating, while the cleaved caspase-3 (CC3) stain shows cell undergoing apoptosis. These spatial variations are governed by variations in the environmental selection forces (note associated difference in GLUT1 and CAIX expression). This continuous but variable birth and death rate permits evolution and can result in both tumor growth and tumor extinction. Note that if the birth/death dynamics remained unchanged, the tumor population in the top panels would become extinct, while the population in the bottom panels would grow rapidly. In small populations, stochastic variations in birth and death rates have a disproportionately large population effect and can result in extinction (adapted from Lloyd et al.; ref. 36).