The development of a technique for the morphometric analysis of invasion in cancer

We describe tests of the feasibility of a reconstructive technique to discriminate between expansive growth and active cell movement in the invasion of tissues by cancer cells. The densities of cancer cells in 2210 microns2 (grid) squares of standard 6 microns fixed, stained histologic sections of a nodule and an invasive cutaneous melanoma were determined, and density maps of the tumors constructed. An abrupt transition from saturation density to zero cell density was observed at the advancing edge (towards the stratum corneum) of the tumor nodule which was consistent with a model for expansion by growth (vis a tergo). In contrast, at the advancing edge of the invasive tumor, the transition from saturation to zero density (towards the subcutaneous tissues) occurred more gradually, over approximately 400 mum, which was consistent with a model for invasion by active movement of melanoma cells. The occurrence of statistically significant "high density regions" near to the advancing edge of the invasive tumor is consistent with an invasive pattern of active movement followed by focal proliferation of the cancer cells, in a repetitious manner. It therefore appears feasible to make kinetic reconstructions of some of the events in invasion, from static quantitative observations.