Expression of growth factors and growth factor receptors in soft tissue tumors. Implications for the autocrine hypothesis.
According to the autocrine hypothesis of cell growth, tumors, in contrast to normal tissue, might simultaneously express both a growth factor and its receptor, resulting in autoregulation and autostimulation of growth. In a related hypothesis, expression of either a growth factor or receptor might allow a tumor to escape exogenous controls on growth, and thereby correlate with malignant potential. Using immunohistochemistry, we investigated these hypotheses in 69 human soft tissue tumors (STT) by assaying for the expression of nerve growth factor and receptor, epidermal growth factor and receptor and platelet-derived growth factor. Both benign (B) and malignant (M) STT expressed a variety of factors and receptors. However, the frequency of any growth factor expression (90% M versus 55% B, p = 0.002) and of multiple factors (59% M versus 24% B, p = 0.006) was significantly greater in malignant tumors. Similarly, expression of any growth factor receptor (73% M versus 31% B, p = 0.001) and of multiple receptors (35% M versus 3% B, p = 0.002) was significantly more frequent in malignant STT. In terms of the autocrine hypothesis, growth factor/receptor co-expression was significantly more common in malignant STT (63% M versus 17% B, p = 0.0002). We conclude that (a) expression of both single and multiple growth factors and receptors was significantly more frequent in malignant STT; (b) support for an autocrine growth mechanism through simultaneous factor/receptor co-expression can be found in both benign and malignant STT; (c) co-expression, however, was more frequent in the malignant tumors; and (d) overall, growth factor and receptor expression, as well as co-expression, was related to biologic potential among human soft tissue tumors.
Perosio
P M
PM
Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia.
Brooks
J J
JJ
D004815:Epidermal Growth Factor / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D006133:Growth Substances / Q000032:analysis*; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000032:analysis; D010306:Parotid Gland / Q000032:analysis; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis*; D017475:Receptors, Nerve Growth Factor; D012983:Soft Tissue Neoplasms / Q000032:analysis / Q000378:metabolism*
D006133:Growth Substances; D009414:Nerve Growth Factors; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D004815:Epidermal Growth Factor; D066246:ErbB Receptors