Correlations between mitotic and apoptotic indices, number of interphase NORs, and histological grading in squamous...

Proliferative activity of tumors is strongly associated with prognosis and response to therapy. The reason for faster and uncontrolled growth rate of tumors compared with normal tissue may be caused by the greater proliferation of cells, the smaller rate of cell death, or both. Cell production vs. cell loss rates, and their correlation with a grade of tumor cell differentiation (G) was estimated in 45 cases of squamous cell lung cancers (SCLC) by the use of mitotic indices (MI), number of interphase NORs, and apoptotic indices (AI) as parameters. The mitotic figures as well as apoptotic cells were observed on paraffin sections (4-microm thick) stained with haematoxylin and eosin, and with Feulgen reaction with Schiff-type reagent containing 0.5% Toluidine Blue. According to our results, all three parameters distinguish significantly (P < 0.05) between well and moderately or poorly differentiated groups, but not between the first two groups, and clearly discriminate between low- and high-grade malignancy. These results suggest classification of squamous cell lung cancers into two groups, a group of low and a group of high proliferative activity, despite their morphological appearance. Regression analysis revealed a significant (P < 0.0005) correlation between MI and AgNOR counts per cell nucleus as proliferative markers and AI as a marker of cell loss. The number of mitoses and apoptoses, especially when they are expressed as a percentage of the total number of tumor cells, are markers of tumor proliferation rate. They both can be used in biofunctional staging, based on cell kinetics, to provide more prognostic information about lung cancers than clinicopathological staging.