Flow cytometric and Ki-67 immunohistochemical analysis of cell cycle distribution of cervical cancer during radiation therapy

Background: Little is known about the cell kinetics of human solid tumors d uring radiation therapy. Materials & Methods: Thirty one patients with cerv ical squamous cell carcinoma were analyzed by flow cytometry and immunohist ochemical staining with Ki-67 antibody for tumor cell kinetics in the early period of radiation therapy. Results: The G0/G1 fraction was significantly larger in stage 3 disease than in stage 2 disease. During radiation therap y, a decrease in the G0/G1 fraction and an increase in the S fraction were observed in stage 3 but not in stage 2 disease. Two reversal patterns of ch ange in the cell cycle appeared in the early period of radiation therapy. T he S phase fraction decreased significantly as the G0/G1 fraction of pre-tr eatment tumors became smaller than 70%, whereas it increased as the G0/G1 f raction became larger than 70%. The S fraction decreased significantly as K i-67 growth fractions of pre-treatment tumors became greater than 30%, but on the contrary, it increased as the Ki-67 growth fraction became smaller t han 30%. Only 2 of 23 patients showed a significant increase of the G2M fra ction, reflecting the presence of the G2 block. The Ki-67 growth fraction i ncreased about 26% at 9 Gy compared with the growth fraction before treatme nt. Tumors which responded well showed higher G0/G1 fractions and lower S f ractions than those which responded badly. Conclusion: The change of cell c ycle parameters of the tumors during radiation therapy suggests that two re versal patterns of changes in cell kinetics take place in the early period of radiation therapy, which may have a potential impact in the modification of radiation therapy.