Correlation between mitotic and Ki-67 labeling indices in paraffin-embedded carcinoma specimens

The mitotic index (MI) and the Ki-67 labeling index (LI) are both understood to measure cellular proliferation, but their relationship is poorly defined. We determined the mitotic index in hematoxylin and eosin-stained paraffin sections of 189 consecutive carcinomas and performed immunohistochemistry on sections from the corresponding blocks using the Ki-67-specific monoclonal antibody Ki-S5. The distributions of MI and LI in the entire series were clearly different, the former fitting a Poisson function in contrast to a broad-tailed unspecific distribution of the latter. Both indices were closely correlated in mammary carcinomas and non-small cell lung cancers, and to a slightly lesser extent in colorectal adenocarcinomas. No significant association was found in small cell lung cancers. In squamous cell carcinomas, the two parameters were inversely correlated. A good agreement between MI and LI values was observed in well-differentiated and moderately well-differentiated cancers regardless of their histological type, whereas in poorly differentiated carcinomas the correlation was not significant. We conclude that MI and LI measure different proliferation characteristics. Their relationship appears to depend on the tumor type and the degree of differentiation. Rather than artifacts due to processing or evaluation techniques, specific differences in cell cycle kinetics are likely to account for these discrepancies.