Sauer C M, Chteinberg E, Rennspiess D, Kurz A K, Zur Hausen A
Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX, Maastricht, Netherlands.
Department of Internal Medicine IV, University Hospital Aachen, Aachen, Deutschland.
Hautarzt. 2017 Mar;68(3):204-210. doi: 10.1007/s00105-017-3945-0.
Merkel cell carcinoma (MCC) is a relatively rare but highly malignant non-melanoma skin cancer of the elderly and immunosuppressed patients. The discovery of the Merkel cell polyomavirus (MCPyV) in 2008 significantly impacted the understanding of the etiopathogenesis of MCC. MCPyV is clonally integrated into the MCC genome and approximately 80% of MCC are MCPyV-positive. Recent results of clinical trials using blockade of the PD-1 immune modulatory pathway are promising for the future treatment of MCC. Despite this major progress of the past few years, the cellular origin of MCC still remains obscure. Based on histomorphology, gene expression profiling, and molecular analyses, we have recently hypothesized that MCC originates from pre‑/pro-B cells. Here we review putative cells of MCC, including Merkel cells, (epi‑)dermal stem cells, and pro‑/pre-B cells. In the present work, the focus is on the concept of pre‑/pro-B cells as the cellular origin of MCC, which might also impact the understanding of other human small cell malignancies of unknown cellular origin, such as small cell carcinomas of the lung and other anatomical locations. In addition, this concept might pave the way for novel treatment options, especially for advanced MCC.
默克尔细胞癌（MCC）是一种相对罕见但高度恶性的非黑色素瘤皮肤癌，好发于老年人及免疫抑制患者。2008年默克尔细胞多瘤病毒（MCPyV）的发现极大地影响了对MCC病因发病机制的理解。MCPyV克隆性整合到MCC基因组中，约80%的MCC为MCPyV阳性。近期使用PD-1免疫调节通路阻断剂的临床试验结果为MCC的未来治疗带来了希望。尽管在过去几年取得了这一重大进展，但MCC的细胞起源仍然不明。基于组织形态学、基因表达谱分析和分子分析，我们最近推测MCC起源于前B/前体B细胞。在此，我们综述了MCC的假定细胞，包括默克尔细胞、（表皮）真皮干细胞和前体B/前B细胞。在本研究中，重点是前体B/前B细胞作为MCC细胞起源的概念，这也可能影响对其他细胞起源不明的人类小细胞恶性肿瘤的理解，如肺癌和其他解剖部位的小细胞癌。此外，这一概念可能为新的治疗选择铺平道路，尤其是对于晚期MCC。
