Towards economy of effort in quantitative ultrastructural pathology: efficient sampling schemes for studying experimental carcinogenesis.

Hamster cheek pouch mucosa was painted with DMBA in order to compare samples of epithelium at different pathological stages of carcinogenesis. Stereological methods were applied to ultrathin sections of tissue to estimate one ultrastructural index of change, the surface ratio of lamina densa compared with the overlying plasma membrane of cells in stratum basale. Analysis of variance techniques were then employed to isolate and quantify the contributions which different levels of sampling (animals, tissue blocks, microscopic fields) made to the total observed variation in this surface ratio. Economical sampling schemes for future use were calculated from the sampling variances by taking into account the relative costs at each sampling level. Though illustrated by means of the hamster cheek pouch-DMBA model, our results are pertinent to many other experimental models for quantitative histopathology.