Immunoreactive a transforming growth factor activity in effusions from cancer patients as a marker of tumor burden and patient prognosis

a Transforming growth factors (α-TGFs) are polypeptides that stimulate anchorage-independent growth of various nontransformed cells in vitro and are believed to be involved in autocrine stimulation of tumor cells. α-TGF activity is secreted by a variety of human cancers leading to the possibility that it may serve as a tumor marker. α-TGF activity was measured in 130 effusions from patients with various types of cancer with a radioimmunoassay using sheep antibodies against the C-terminal 17 amino acids of linear rat α-TGF. Forty-two % of the effusions contained immunoreactive a transforming growth factor (Ir-α-TGF) activity, including 13 of 34 (38%) breast cancer, 12 of 24 (50%) lung cancer, and 13 of 31 (42%) ovarian cancer specimens. Concentrations ranged from 1.56 to 50 ng/ml. Only 3 of 17 control effusions from noncancer patients had low levels of activity, all less than 2 ng/ml. The presence of Ir-α-TGF activity correlated with patients^' performance status (PS) and tumor burden. It was present in 18 of 67 (27%) effusions of patients with PS ≤ 2 and in 23 of 33 (70%) with PS 3 or 4 (P < 0.0001). Only 2 of 43 (4%) patients with one site of metastatic disease had detectable Ir-α-TGF (mean, 0.23 ng/ml); 18 of 37 (48%) with two sites (mean, 5.22 ng/ml, P < 0.0001); and 33 of 34 (97%) with > two sites (mean, 5.93 ng/ml, P = 0.002). It was present in a larger percentage of effusions from breast cancer patients with estrogen- and progesterone receptor-negative tumors. Univariate analysis revealed that detectable Ir-α-TGF activity, PS 3 or 4, and the number of sites of disease correlated with a shorter survival. Only Ir-α-TGF and PS 3 or 4 retained significance in a multivariate analysis. In conclusion, Ir-α-TGF is frequently detectable in effusions from cancer patients, it correlates with other known adverse prognostic factors, and its presence predicts for a poor survival. Further studies of α-TGF activity in more readily accessible body fluids such as serum or urine are warranted.