Expression of Bcl-2, p53, c-jun and c-fos protooncogenes in keloids and hypertrophic scars

Keloids and hypertrophic scars represent a model of altered wound healing c haracterized by overproduction of extracellular matrix and dermal fibroblas ts with high mitotic rate. Alteration of apoptosis and cell proliferation h as been implicated in the etiology of keloids. The bcl-2 protooncogene enco des a protein that protects cells from programmed cell death while p53 prot ein functions as negative regulator of cell proliferation. Both protooncoge nes have been shown to play a role in tissue homeostasis as apoptotic regul atory genes. The c-jun and c-fos protooncogenes are transactivating factors also involved in fibroblast proliferation. In our study we investigated, b y immunohistochemistry. skin specimens from three clinically active hypertr ophic scars and keloids, two resting keloids and two early phase morphea to detect both bcl-2 and p53 protein expression, in order to evaluate these a poptotic regulatory genes in different fibrotic conditions. The c-jun and c -fos, at protein and mRNA level, and Ki67 nuclear antigen expression were a lso investigated. In hypertrophic scars and active keloids we could detect intense Bcl-2 staining in basal keratinocytes and in scattered fibroblast-l ike and perivascular spindle-shaped cells, while no p53 expression could be demonstrated. The c-jun and c-fos mRNA and protein expression was mainly f ound in dermal fibroblast-like cells and elongated perivascular cells in al l skin biopsies, and similar immunostaining pattern was observed for Ki67 a ntigen. No protooncogene expression in morphea patients and normal skin, un less Bcl-2 staining in the basal layer of normal epidermis, was documented. Our results suggest that Bcl-2, c-jun and c-fos protein expression and lac k of p53 detection in fibroblast-like and perivascular spindle cells are re lated to increased fibroblast proliferation, confirmed by Ki67 positivity, probably due to alteration of these regulatory apoptotic genes resulting in pathological scarring. (C) 1999 Elsevier Science Ireland Ltd. All rights r eserved.