title: Immunoreactive alpha transforming growth factor activity in effusions from cancer patients as a marker of tumor burden and patient prognosis.
abstract: alpha Transforming growth factors (alpha-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. alpha-TGF activity is secreted by a variety of human cancers leading to the possibility that it may serve as a tumor marker. alpha-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 alpha-TGF. Forty-two % of the effusions contained immunoreactive alpha transforming growth factor (Ir-alpha-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-alpha-TGF activity correlated with patients' performance status (PS) and tumor burden. It was present in 18 of 67 (27%) effusions of patients with PS less than or equal to 2 and in 23 of 33 (70%) with PS 3 or 4 (P less than 0.0001). Only 2 of 43 (4%) patients with one site of metastatic disease had detectable Ir-alpha-TGF (mean, 0.23 ng/ml); 18 of 37 (48%) with two sites (mean, 5.22 ng/ml, P less than 0.0001); and 33 of 34 (97%) with greater than 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-alpha-TGF activity, PS 3 or 4, and the number of sites of disease correlated with a shorter survival. Only Ir-alpha-TGF and PS 3 or 4 retained significance in a multivariate analysis. In conclusion, Ir-alpha-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 alpha-TGF activity in more readily accessible body fluids such as serum or urine are warranted.
authors.affiliation: University of Texas Health Science Center, San Antonio, Division of Medical Oncology 78284.
authors.forename: C L
authors.initials: CL
authors.lastname: Arteaga
authors.forename: A R
authors.initials: AR
authors.lastname: Hanauske
authors.forename: G M
authors.initials: GM
authors.lastname: Clark
authors.forename: C K
authors.initials: CK
authors.lastname: Osborne
authors.forename: P
authors.initials: P
authors.lastname: Hazarika
authors.forename: R L
authors.initials: RL
authors.lastname: Pardue
authors.forename: F
authors.initials: F
authors.lastname: Tio
authors.forename: D D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: D001202:Ascitic Fluid / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000032:analysis* / Q000401:mortality; D010455:Peptides / Q000032:analysis* / Q000276:immunology; D010996:Pleural Effusion / Q000378:metabolism; D011379:Prognosis; D015291:Transforming Growth Factors
chemical_list: D014408:Biomarkers, Tumor; D010455:Peptides; D015291:Transforming Growth Factors