Immunohistochemical evidence of nerve growth factor in Dupuytren's diseased palmar fascia

Purpose: Histologically, the pathognomic feature of Dupuytren's contracture (DC) is the myofibroblast. Its occurrence in this disease has been associated with local production of transforming growth factor (TGF)-B. However, nerve growth factor (NGF) is a recognized growth factor involved in wound healing and has been shown to induce the myofibroblast phenotype in cultured fibroblasts. We hypothesized that NGF would be abundant in this disease entity. Methods: Immunohistochemistry was used to examine for the presence of NGF in 25 surgical specimens from patients with DC and in surgical specimens from 5 other, unrelated procedures. Patient demographics showed that nearly all patients were men, with a mean age of 61 years (range 36-77). Serial sections were probed with antibodies, stained, and then digitally photomicrographed. Disease staging was also performed. Image analysis was then used to measure the percentage of area stained. In addition, representative sections were probed for TrkA, the high-affinity receptor for NGF, and alpha-smooth muscle actin, a cytoskeletal marker of the myofibroblast phenotype. These alternate steps were used to infer functional dependence and the association of NGF with myofibroblast populations. Results: Histologically, all patients had either stage II or III disease. Biopsy results showed an abundance of NGF-over double that of controls. The highest levels of NGF occurred in hypercellular stage II disease. In addition, we confirmed that NGF is linked to the expression of both TrkA receptors and alpha-smooth muscle actin. Conclusions: Tissue levels of NGF are elevated in Dupuytren's disease. This tissue is competent to respond to NGF and manifests an abundance of myofibroblasts in areas of NGF expression. Nerve growth factor is most apparent in the proliferative (hyperplastic) stage of the disease. These data infer that NGF is linked to the pathologic process.