Division of Cancer Medicine, Departmentof Investigational Cancer Therapeutics, Phase I Clinical Trials Program, MD Anderson Cancer Center, Houston, TX 77030, USA.
JAMA Dermatol. 2013 Mar;149(3):322-6. doi: 10.1001/jamadermatol.2013.2023.
Approximately 10% to 25% of patients treated with BRAF inhibitors develop cutaneous squamous cell carcinoma (SCC), but the mechanism responsible has not yet been determined. We report what we believe to be the first case in which Merkel cell polyomavirus (MCPyV) and human papillomavirus subtype 17 (HPV-17) were associated with cutaneous SCC that developed during treatment with the BRAF inhibitor dabrafenib.
A 62-year-old woman with V600E BRAF -mutant metastatic melanoma enrolled in a phase 1 trial of dabrafenib, a selective inhibitor of V600-mutant BRAF kinase. During the first 6 weeks of treatment, the patient developed multiple skin lesions, including a 6-mm crusted papule on the left eyebrow, which was resected and, on pathology examination, revealed SCC. The DNA extracted from paraffin-embedded tissue was amplified by polymerase chain reaction for detection of MCPyV and epidermodysplasia verruciformis HPV (EV-HPV) types. Analysis of the cloned and sequenced polymerase chain reaction products revealed the presence of MCPyV and HPV-17 DNA. Other EV-HPV subtypes were not detected.
To our knowledge, this is the first report demonstrating the coexistence of MCPyV and HPV-17 in cutaneous SCC. Because both viruses have oncogenic potential, their role in the development of BRAF inhibitor-related SCC merits further investigation.
大约 10%至 25%接受 BRAF 抑制剂治疗的患者会发展为皮肤鳞状细胞癌(SCC),但导致这种情况的机制尚未确定。我们报告了首例据信与接受 BRAF 抑制剂达拉非尼治疗期间发生的皮肤 SCC 相关的 Merkel 细胞多瘤病毒(MCPyV)和人乳头瘤病毒 17 型(HPV-17)的病例。
一名 62 岁女性患有 V600E BRAF 突变转移性黑色素瘤,入组了达拉非尼的 1 期临床试验,达拉非尼是一种 V600 突变 BRAF 激酶的选择性抑制剂。在治疗的前 6 周,患者出现了多个皮肤病变,包括左眉毛上的一个 6 毫米的结痂丘疹,该丘疹被切除,病理检查显示 SCC。从石蜡包埋组织中提取的 DNA 通过聚合酶链反应进行扩增,以检测 MCPyV 和疣状表皮发育不良型 HPV(EV-HPV)型。对聚合酶链反应产物的克隆和测序分析显示存在 MCPyV 和 HPV-17 DNA。未检测到其他 EV-HPV 亚型。
据我们所知,这是首例报告表明 MCPyV 和 HPV-17 共同存在于皮肤 SCC 中。由于这两种病毒都具有致癌潜能,因此它们在 BRAF 抑制剂相关 SCC 发展中的作用值得进一步研究。