Chemoradiation-induced expression of fibroblast growth factor-2 and laminin in patients with cervical cancer.
OBJECTIVE
To investigate the protein expression change of FGF2 in cervical cancers during chemoradiotherapy, as indicated in our previous study using microarray analysis. In addition, we sought to examine the predictive value of such changes in expression for disease failure after chemoradiotherapy.


METHODS
Biopsy specimens were obtained from 35 patients with cervical cancers before (pretreatment) and 1 week after initiation (midtreatment) of chemoradiotherapy (CRT) (9 Gy and 40 mg/m(2) of cisplatin). Immunohistochemical studies (IHS) were performed to detect FGF2, laminin and CD44 expression using an automated streptavidin-biotin immunoperoxidase staining system. Positive area proportion (%) of FGF2 and CD44 were analyzed using an image analysis system and laminin staining pattern was scored by continuity of the basement membrane immunopositivity. Patients were defined as good (n = 18) or poor responders (n = 10) based on their two-year disease-free survival.


RESULTS
Protein expression of FGF2 in midtreatment samples (mid) was significantly higher than in pretreatment samples (pre). Discontinuity of laminin staining pattern in mid was significantly higher than in pre. Protein expression of CD44 was not significantly different between mid and pre. The ratio change (mid versus pre) of FGF2 expression in poor responders was significantly lower than that in good responders (p < 0.05). The number of cases with discontinuity of laminin staining pattern at pre was significantly increased in the poor responders (p < 0.05). Ratio changes of FGF2 or CD44 expression in mid correlated with laminin staining pattern in pre.


CONCLUSIONS
Using biopsy specimens from pretreatment and midtreatment cervical cancers, we revealed significant changes in FGF2 protein expression during fractionated radiotherapy with cisplatin. We also found that FGF2 ratio change and laminin discontinuity staining pattern at pretreatment were significantly associated with prognosis. These molecular features might help us to identify patients at high risk of disease failure after CRT.
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
Tamaki
Tomoaki
T
Imadome
Kaori
K
Sakai
Minako
M
Tsujii
Hirohiko
H
Imai
Takashi
T
D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis* / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000401:mortality / Q000628:therapy*
D018960:Hyaluronan Receptors; D007797:Laminin; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2