Change in fibroblast growth factor 2 expression as an early phase radiotherapy-responsive marker in sequential biopsy samples from patients with cervical cancer during fractionated radiotherapy.
BACKGROUND
The authors previously demonstrated that fibroblast growth factor 2 (FGF2) expression levels in tumor cells (FGF2-T) may be an indicator of the efficacy of radiotherapy in patients with cervical cancer (CC). In the current study, this finding was extended in newly enrolled patients and was investigated further in stromal FGF2 (FGF2-S) expression.


METHODS
Sixty-nine patients with CC were recruited as a validation set for the immunohistochemical detection of FGF2-T from biopsy samples that were taken before (pretreatment) or 1 week after the initiation of radiotherapy (midtreatment). The authors also investigated the expression of FGF2 in tumor FGF2-S and investigated vascular endothelial growth factor (VEGF), and cluster of differentiation 31 (CD31) (also called platelet endothelial cell adhesion molecule) in these patients and in an additional 35 patients from a previous study.


RESULTS
FGF2 expression was detected in tumor cells from all patients and in stromal cells from 87% of patients. FGF2-T was significantly higher in midtreatment samples (P=.0002), and a high ratio of midtreatment/pretreatment FGF2-T was related significantly to a better prognosis (P=.025). Increased VEGF expression after the initiation of radiotherapy was related significantly to positive FGF2-S in pretreatment samples (P=.035); however, it was not related to prognosis or microvessel density detected by CD31 expression.


CONCLUSIONS
Radiation causes a response in tumor cells and adjacent normal cells and changes the extracellular matrix environment. In this study, the authors confirmed their previous findings and demonstrated that changes in FGF2-T expression may be used as a marker to monitor the effectiveness of radiotherapy in patients with CC. These findings should improve patient selection for molecular targeted therapies, such as cytokine inhibitors, after standard-of-care treatment.
Nakawatari
Miyako
M
RadGenomics Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
Iwakawa
Mayumi
M
Ohno
Tatsuya
T
Kato
Shingo
S
Nakamura
Etsuko
E
Ohkubo
Yu
Y
Tamaki
Tomoaki
T
Imai
Takashi
T
D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy / Q000379:methods; D019583:Dose Fractionation, Radiation; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000528:radiation effects*; D006801:Humans; D051379:Mice; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014408:Biomarkers, Tumor; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2