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 characterized by overproduction of extracellular matrix and dermal fibroblasts with high mitotic rate. Alteration of apoptosis and cell proliferation has been implicated in the etiology of keloids. The bcl-2 protooncogene encodes a protein that protects cells from programmed cell death while p53 protein functions as negative regulator of cell proliferation. Both protooncogenes have been shown to play a role in tissue homeostasis as apoptotic regulatory genes. The c-jun and c-fos protooncogenes are transactivating factors also involved in fibroblast proliferation. In our study we investigated, by immunohistochemistry, skin specimens from three clinically active hypertrophic 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 apoptotic regulatory genes in different fibrotic conditions. The c-jun and c-fos, at protein and mRNA level, and Ki67 nuclear antigen expression were also investigated. In hypertrophic scars and active keloids we could detect intense Bcl-2 staining in basal keratinocytes and in scattered fibroblast-like and perivascular spindle-shaped cells, while no p53 expression could be demonstrated. The c-jun and c-fos mRNA and protein expression was mainly found in dermal fibroblast-like cells and elongated perivascular cells in all skin biopsies, and similar immunostaining pattern was observed for Ki67 antigen. No protooncogene expression in morphea patients and normal skin, unless 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 lack of p53 detection in fibroblast-like and perivascular spindle cells are related to increased fibroblast proliferation, confirmed by Ki67 positivity, probably due to alteration of these regulatory apoptotic genes resulting in pathological scarring.

Classification of non-Hodgkin malignant lymphomas of the skin.

The authors subdivide the primary non-Hodgkin cutaneous malignant lymphomas into "proper" and "non-proper" types. "Proper" lymphomas are those which have in the skin their proper site of localization, and include mycosis fungoides, Pagetoid reticulosis, Baccaredda-Sézary syndrome and possibly lymphomatoid papulosis. They are T-cell lymphomas arising in the papillary dermis, characterized by epidermotropism, having a specific clinical feature in that they are unlikely to be simulated by other cutaneous malignant lymphomas. "Non-proper" lymphomas are those which do not usually arise in the skin, but in various other organs. They are B-, T- or null-cell lymphomas, arising in the middle dermis, infrequently epidermotropic, having a papular-nodular-tumoural clinical feature, which are indistinguishable clinically from other neoplastic types such as plasmacytoma and Hodgkin's disease. The three classifications of non-Hodgkin lymphomas most followed are not directly applicable to cutaneous lymphomas because some of the former are not primarily sited in the skin, and because a follicular morphology is infrequently seen in the latter. Whereas the first classification reported for cutaneous lymphomas utilized malignancy as a criterion, the present classification here proposed utilizes the propriety of the site of localization as the criterion for subdivision into "proper" and "non-proper" types.

Malignant melanoma of the oral cavity.

The authors recount three cases of malignant melanomas in the oral cavity. The first was classified as malignant melanoma in situ, pagetoid type; the second as malignant melanoma, dendritic type; and the third as nodular malignant melanoma. These cases led the authors to compare the histopathologic features of malignant melanomas of the oral cavity with those of malignant melanomas of the skin and, finding them much the same, to advise early biopsies of all pigmented lesions in the oral cavity.