Department of Dermatology, Asan Medical Center, SongPa-Gu PyongNab-Dong, Seoul 138-736, Korea.
Br J Dermatol. 2010 Feb 1;162(2):371-9. doi: 10.1111/j.1365-2133.2009.09536.x. Epub 2009 Nov 9.
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.
We assayed expression of inflammatory cytokines [interleukin (IL)-1alpha, 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.
Filaggrin expression decreased and expression of involucrin, various inflammatory markers (IL-1alpha, 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-1alpha and TNF-alpha was observed in perilesions as in the lesions.
The early inflammatory events (IL-1alpha 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.
表皮生长因子受体（EGFR）对肿瘤细胞分裂、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，最常见的是脓疱性皮疹和皮肤干燥。
我们检测了炎症细胞因子（白细胞介素（IL）-1α、肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ、人类白细胞抗原（HLA）-DR 和细胞间黏附分子（ICAM）-1）、分化标志物（丝聚合蛋白、兜甲蛋白和桥粒芯糖蛋白 1）和磷酸化 EGFR（pEGFRs）在脓疱性皮疹中的表达，以确定这些标志物与西妥昔单抗引起的皮疹之间的关系。
患者/方法：从接受西妥昔单抗治疗的结肠癌患者中选择 12 个脓疱性病变活检。进行免疫组织化学和共聚焦激光扫描显微镜免疫荧光检测。
在脓疱性皮疹中，丝聚合蛋白表达减少，兜甲蛋白、各种炎症标志物（IL-1α、TNF-α、ICAM-1 和 HLA-DR）表达增加，pEGFR 表达明显下调。在病变周围，与毛囊间表皮相比，毛囊中 pEGFR 表达减少。病变周围也观察到 IL-1α 和 TNF-α 的增加。
早期炎症事件（IL-1α 和 TNF-α 的表达）和病变周围毛囊中 pEGFR 的缺乏表明，EGFR 抑制引起的炎症事件可能与异常分化一起引发脓疱性皮疹。西妥昔单抗引起的皮肤干燥可能与丝聚合蛋白的减少有关。
