Cervical carcinoma DNA content, S-fraction, and malignancy grading. I. Interrelationships

The flow cytometric measured DNA content (i.e., DNA index), S-fractions, and histopathologic malignancy grades were studied for ninety uterine cervical squamous cell carcinomas using tissue biopsies taken prior to radiotherapy. The DNA aneuploidy frequency for low S-phase tumors (%S < 14) was only 9 29 (31%) compared to 22 30 (73%) for intermediate (%S 15-23) and 30 31 (97%) for high (%S > 24) tumors. An overall mean %S of 20 ± 7 (range 2-45%) was observed for these cervical cancers, with the S-fraction significantly increasing (P = < 0.01) from 12 ± 5, to 18 ± 8, and 26 ± 7 for diploid/near diploid, low-degree DNA aneuploidy, and high-degree DNA aneuploidy tumors, respectively. Broad heterogeneity was observed for the microscopic scored malignancy grades within DNA index and the cell-cycle S-fraction subgroups. Generally, multifactorial histopathology scoring was not significantly correlated with either the tumor DNA index or %S variables. Based on statistical analysis, the malignancy grades more closely reflected the tumor proliferative activity than the DNA index, with nuclear polymorphism, mitotic frequency, and the invasion pattern showing the lowest P values (which were not significant at P = 0.05). High tumor S-fraction was associated with high malignancy grade, as evidenced by 19 25 (75%) of high S-fraction, high degree DNA aneuploidy tumors having >average malignancy grade compared to only 2 14 (14%) low to moderate S-fraction tumors having similar DNA index. The results indicate that more reliable identification of biologically different cervical cancers can be achieved by evaluating the tumor DNA index in relationship to the cell-cycle %S and malignancy grading.