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 during radiation therapy.


METHODS
Thirty one patients with cervical squamous cell carcinoma were analyzed by flow cytometry and immunohistochemical 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 therapy, 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 change in the cell cycle appeared in the early period of radiation therapy. The S phase fraction decreased significantly as the G0/G1 fraction of pre-treatment tumors became smaller than 70%, whereas it increased as the G0/G1 fraction became larger than 70%. The S fraction decreased significantly as Ki-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 than 30%. Only 2 of 23 patients showed a significant increase of the G2M fraction, reflecting the presence of the G2 block. The Ki-67 growth fraction increased about 26 % at 9 Gy compared with the growth fraction before treatment. Tumors which responded well showed higher G0/G1 fractions and lower S fractions than those which responded badly.


CONCLUSIONS
The change of cell cycle parameters of the tumors during radiation therapy suggests that two reversal 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.
Higuchi
K H
KH
Division of Radiation Medicine, National Institute of Radiological Sciences, Chiba-shi, Japan.
Nakano
T
T
Tsuboi
A
A
Suzuki
Y
Y
Ohno
T
T
Oka
K
K
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D016193:G1 Phase / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D016192:Resting Phase, Cell Cycle / Q000502:physiology / Q000528:radiation effects; D016196:S Phase / Q000502:physiology / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*
D004273:DNA, Neoplasm; D019394:Ki-67 Antigen