Mitotic rate, DNA distribution, and chromatin in situ sensitivity to heparin in breast cancer.
The purpose of this study was to characterize breast carcinomas by cell kinetic parameters. Mitotic rate (MR) and flow cytometrically (FCM) measured cell cycle distribution as well as chromatin testing in situ employing heparin for determination of activated chromatin, provided the following results: MR counted in 73 unselected carcinomas showed an increase up to a tumor size of 4.2 cm (p less than 0.05); beyond this diameter, the MR was found to decrease. In T1-T2 carcinomas, cell cycle stage analysis yielded higher percentages of cells in S and G2M phase for ductal (13% and 12%, N = 22) than for lobular (8% and 7%, N = 8) node-negative carcinomas (p less than 0.002). In ductal carcinomas, lymph node involvement was reflected by higher % G2M values (15%, N = 26) compared with negative cases (12%, N = 22) (p less than 0.05). Ductal node-positive T3-T4 carcinomas (N = 10) revealed a higher % S value (16%) than their T1-T2 counterparts. A correlation between MR and % G2M was established only up to a tumor size of 4.2 cm (r = 0.39, p less than 0.05). A highly sensitive ('H') and a poorly sensitive ('P') subgroup of carcinomas with respect to heparin-induced changes in fluorescence intensity of the G1/0 peak of the DNA aneuploid cell line were identified, as previously shown. These subgroups were here updated with a larger number of carcinomas and were limited to T1-T2 cancers (N = 57). Group 'H' included more younger patients (p less than 0.005), less cases with nodal involvement in ductal carcinomas (p less than 0.05), and lower % G2M values in lobular node-negative cases (p less than 0.05), than group 'P'. DNA diploid cells always existing in DNA aneuploid carcinomas are more sensitive than their aneuploid counterparts (p less than 0.01); however, they strengthen the stratification to 'H' and 'P'. We suggest 'H' carcinomas to be less aggressive than 'P' carcinomas. Small breast carcinomas are recommended to cell kinetic investigations for individualizing adjuvant therapy.