Investigation of papulopustular eruptions caused by cetuximab treatment shows altered differentiation markers and increases in inflammatory cytokines
Investigation of papulopustular eruptions caused by cetuximab treatment shows altered differentiation markers and increases in inflammatory cytokines
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DOI：
10.1111/j.1365-2133.2009.09536.x
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发表时间：
2010-02-01
影响因子：
10.3
通讯作者：
Ryu, M. H.
中科院分区：
文献类型：
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作者：
Han, S. S.;Lee, M.;Ryu, M. H.
背景表皮生长因子受体（EGFR）对肿瘤细胞的分裂、存活和转移有重要的调控作用.抑制EGFR的药物已被用于治疗晚期恶性肿瘤，但会引起不同的皮肤副作用，最常见的是丘疹脓疱性皮疹和干燥症。目的我们测定了炎性细胞因子[白细胞介素（IL）-1 α，肿瘤坏死因子（TNF）-α，干扰素（IFN）-γ，人白细胞抗原（HLA）-DR和细胞间粘附分子（ICAM）-1]的表达，分化标志物（丝聚蛋白，外皮蛋白和兜甲蛋白）和磷酸化EGFR（pEGFRs）在丘疹脓疱性皮疹，以确定这些标志物和西妥昔单抗引起的皮疹之间的关联。结果丘疹脓疱性出疹中Filaggrin表达降低，外皮蛋白、IL-1 α、TNF-α、ICAM-1和HLA-DR表达升高，pEGFR表达明显下调。在皮损周围，与毛囊间表皮相比，毛囊中的pEGFR表达降低。IL-1 α和TNF-α的增加被观察到在perilisions在lassions.Conclusions的早期炎症事件（IL-1 α和TNF-α的表达），和缺乏pEGFR在perilision卵泡，表明炎症事件诱导的EGFR抑制可能会引发丘疹脓疱性皮疹沿着与分化的改变。丝聚蛋白的减少可能参与了西妥昔单抗引起的干燥症的发病机制。
Background Epidermal growth factor receptor (EGFR) critically regulates tumour cell division, survival and metastasis. Agents that inhibit EGFR have been used in the treatment of advanced-stage malignancies, but cause variable cutaneous side-effects, most often papulopustular eruptions and xerosis.Objectives We assayed expression of inflammatory cytokines [interleukin (IL)-1 alpha, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, human leucocyte antigen (HLA)-DR and intercellular adhesion molecule (ICAM)-1], differentiation markers (filaggrin, involucrin and loricrin) and phosphorylated EGFRs (pEGFRs) in papulopustular eruptions to determine the association between these markers and the eruptions caused by cetuximab.Patients/methods Twelve papulopustular lesion biopsies were selected from patients with colon cancer who had received cetuximab treatment. Immunohistochemistry and immunofluorescence with a confocal laser scanning microscopy were performed.Results Filaggrin expression decreased and expression of involucrin, various inflammatory markers (IL-1 alpha, TNF-alpha, ICAM-1 and HLA-DR) increased and the expression of pEGFR was markedly downregulated in papulopustular eruptions. In perilesions, decreased pEGFR expression was noted in hair follicles compared with interfollicular epidermis. The increase of IL-1 alpha and TNF-alpha was observed in perilesions as in the lesions.Conclusions The early inflammatory events (IL-1 alpha and TNF-alpha expression) seen, and the lack of pEGFR in perilesional follicles, indicate that inflammatory events induced by EGFR inhibition may initiate papulopustular eruptions along with the altered differentiations. The decrease of filaggrin may contribute to the pathogenesis of the xerosis caused by cetuximab.