TOTAL NUMBER OF CANCER CELL-NUCLEI AND MITOSES IN BREAST-TUMORS ESTIMATED BY THE OPTICAL DISECTOR

OBJECTIVE: The total number of cancer cell nuclei, N(nuc), and of mito ses, N(mit), in the primary lesion are potentially important indicator s of tumor biology. In the present study, such estimates were obtained on breast cancers by an unbiased stereologic method. STUDY DESIGN: Th e total number estimates are the product of two variables: (1) the vol ume of tumor, V(T), estimated by the Cavalieri principle, and (2) the densities of cancer cell nuclei and of mitoses obtained in small, thre e-dimensional samples (i.e., optical disectors) of 40-mu m-thick metha crylate sections, which were selected systematically at random from th e whole specimen. RESULTS: In 93 prospectively collected tumors, N(nuc ) ranged from 0.06 to 7.9.10(9) (median, 0.6.10(9)), and N(mit) ranged from 0.02 to 64.10(6) (median, 1.5.10(6)). Both N(nuc) and N(mit) cor related significantly with V(T) (r = .77 and .60, respectively); howev er, the steep slopes of the regression lines indicated that densities of nuclei and mitoses increased as a function of tumor size. On averag e, N(mit) and estimates of mitotic frequency tended to be larger in ly mph node-positive patients as compared with lymph node-negative ones ( 2P less than or equal to .08), whereas no such relation teas found for nuclear counts (2P greater than or equal to .40). By counting a media n number of 195 nuclei and 28 mitoses per tumor, the average coefficie nts of error of N(nuc) and N(mit) were 17% and 32%, respectively; this gave seemingly sufficient precision as compared with the huge interpa tient variation in estimates, 180% and 490%. Moreover, the intraobserv er reproducibility of density estimates was excellent (r greater than or equal to .88). CONCLUSION: The present study showed the feasibility , efficiency and reproducibility of the unbiased optical disector prin ciple applied to human breast cancer and provided data on new paramete rs of biologic relevance. The technique seems suitable for use in expe rimental oncology, but further studies are needed to investigate its c linical value.