Cg. Li et al., TGF-beta 1 levels in pre-treatment plasma identify breast cancer patients at risk of developing post-radiotherapy fibrosis, INT J CANC, 84(2), 1999, pp. 155-159
A serious complication of radiotherapy in the treatment of cancer patients
is the late onset of fibrosis in normal tissues. Transforming growth factor
13 (TGF-beta) is emerging as a key mediator of the fibrotic process throug
h its effects on stimulation of fibroblast proliferation, migration and ext
racellular matrix (ECM) synthesis. The fact that radiation-induced vascular
injury tends to precede the development of fibrosis has led to the suggest
ion that vascular damage is crucial in its pathogenesis. CD105, the specifi
c type III vascular receptor for TGF-beta 1 and -beta 3, modulates cell pro
liferation and ECM production in response to TGF-beta in vitro. In this stu
dy, we have quantified the levels of TGF-beta 1 and soluble CD105-TGF-beta
1 complex in 91 pre-radiotherapy plasma samples from early-stage (T1 or T2)
breast cancer patients utilising an enhanced chemiluminescence ELISA syste
m. During the follow-up period, 24 patients had developed moderate and one
severe fibrosis of the breast. The mean TGF-beta 1 level in these 25 patien
ts was 203.2 +/- 37.3 pg/ml, which was significantly elevated above the lev
el for those with no fibrosis. Furthermore, a significantly lower CD105-TGF
-beta 1 complex level was observed in the former compared to the latter. Sp
earman's correlation analysis showed that TGF-beta 1 was positively correla
ted and the CD105-TGF beta 1 complex inversely correlated with the occurren
ce of breast fibrosis. Using a cut off value of 96 pg/ml, the sensitivity a
nd specificity of TCF-beta 1 revels in predicting breast fibrosis were 76%
and 74%, respectively. Our results indicate that TGF-beta 1 and the recepto
r-ligand complex appear to be of clinical value in identifying patients at
risk of developing post-radiotherapy fibrosis. Int. J. Cancer (Pred. Oncol.
) 84: 155-159, 1999. (C) 1999 Wiley-Liss, Inc.