Sequential effects of photodynamic treatment of basal cell carcinoma.

BACKGROUND: Photodynamic therapy (PDT) of superficial basal cell carcinoma (SBCC) acts as a biological response modifier or killing target cells, but sequential biological effects have not been reported in depth in humans. METHODS: In 15 patients with SBCC treated with aminolevulinic acid (ALA)-PDT, inflammatory infiltrate, apoptosis phenomena and tumor-derived molecules were investigated on biopsies at baseline, and after 15 min and 4, 24, 48 and 72 h, by immunohistochemistry and ultrastructure. RESULTS: Early apoptosis of keratinocytes was already observed at 15 min, while late apoptotic markers were maximally found at 24 h. Baseline mast cells tended to slightly increase up to 72 h; polymorphonuclear phagocytes significantly increased at 4 h but decreased at 24/48/72 h; on the contrary, lymphocytes and macrophages gradually increased starting at baseline. At baseline, SBCC cells expressed stem cell factor in all cases, and granulocyte-monocyte colony-stimulating factor, basic fibroblastic growth factor, interleukin (IL)-8 and vascular endothelial growth factor in most cases. IL-6 and monocyte chemoattractant protein-1 were poorly expressed, and transforming growth factor-beta was absent. CONCLUSIONS: We show a clear time-dependent profile of apoptotic markers and inflammatory infiltrate composition in SBCC after ALA-PDT. SBCC cells express cytokines and chemotactic molecules that are likely related to the recruitment of inflammatory cells.

Fibrosis in regressing melanoma versus nonfibrosis in halo nevus upon melanocyte disappearance: could it be related to a different cytokine microenvironment?

BACKGROUND: It is not clear why melanocyte disappearance occurs without fibrotic evolution in halo nevus and with fibrotic evolution in regressing melanoma. METHODS: Six halo nevi, seven regressing primary melanomas, and seven primary melanoma (PM) without regression were studied using immunohistochemistry for the phenotype of inflammatory infiltrate and the expression of cytokines involved in fibrogenesis or macrophage regulation. Melanocytes were also evaluated using electron microscopy. RESULTS: CD8(+) lymphocytes predominated in halo nevus, whereas CD4(+) lymphocytes prevailed in melanoma; a few macrophages were only found in melanoma. Fibrogenic cytokines, IL-6, platelet-derived growth factor, and transforming growth factor-beta were only expressed in melanoma, whereas basic fibroblastic growth factor was also expressed in halo nevus. Antifibrotic cytokine tumor necrosis factor (TNF)-alpha was expressed at a higher degree in halo nevus. Cytokines involved in macrophage regulation were only expressed in melanoma. CONCLUSIONS: Fibrogenic cytokines were more frequently expressed in melanoma than in halo nevus, irrespective of regression. At ultrastructural level, melanocytes showed a more activated status in regressing melanoma than in halo nevus, in compliance with a milieu richer in cytokines. Although the cytokine microenvironment does not completely justify the fibrotic evolution in regressing PM, the higher TNF-alpha expression in halo nevus suggests a possible role in nonfibrotic evolution of this lesion.

New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions.

Vitiligo is a skin disease that is caused by selective destruction of melanocytes and is characterized by white spots. Melanocytes and keratinocytes seem to exhibit a functional close relationship, mediated at least in part by keratinocyte-derived cytokines, which seem important for survival and activity of melanocytic cells. We wanted to investigate the hypothesis that in vitiligo the expression of epidermal cytokines may be modified compared with normal skin. In 15 patients with active, non-segmental vitiligo, biopsies were obtained from lesional, perilesional and non-lesional skin; normal skin from five healthy donors was also tested. Tissue sections were tested using immunohistochemistry for the expression of keratinocyte-derived cytokines with stimulating activity, such as granulocyte-monocyte colony stimulating factor (GM-CSF), basic fibroblastic growth factor (bFGF), and stem cell factor (SCF) or with inhibiting activity, such as interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) on melanocytes. Cytokine receptors and specific melanocytic markers were also investigated. No melanocyte was identified in lesional skin by means of specific markers or c-kit receptor, whereas in perilesional, non-lesional and healthy skin, melanocytes were found in similar number. In vitiligo skin a significantly lower expression of GM-CSF, bFGF and SCF was found, and a significantly higher expression of IL-6 and TNF-alpha was detected, compared with perilesional, non-lesional and healthy skin. In conclusion, we provided evidence that a significant change of epidermal cytokines exists in vitiligo skin compared with perilesional, non-lesional and healthy skin, suggesting that the cytokine production of epidermal microenvironment may be involved in vitiligo.