Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Pathol Int. 2021 May;71(5):337-347. doi: 10.1111/pin.13090. Epub 2021 Mar 22.
Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that tends to show local recurrence and metastasis. Typically, MCC is polyomavirus (MCPyV)-associated and cytokeratin 20 (CK20) positive. However, little is known about this tumor and its origins. Here, we aimed to determine the developmental origins of MCC and to identify prognostic clinicopathologic factors. Initial examinations revealed that CK20 and MCPyV expression (CK20+, MCPyV+ (60%); CK20+, MCPyV- (10%); CK20-, and MCPyV- (30%)) did not affect overall survival. With RB1 gene sequencing of FFPE specimens, which covered an entire exon, all RB1 mutation-positive cases showed positive regional lymph node and/or distant metastases (8/8 cases, 100%), whereas the frequency of the metastasis was statistically significantly lower in RB1 mutation-negative cases, (10/16 cases, 62%, P = 0.033). The results were also confirmed with immunohistochemistry, and either RB1 alterations, entire exon sequencing, or immunohistochemistry was associated with the metastasis (P = 0.007). RB1 alterations may be used to access the aggressive clinical course of MCC.
默克尔细胞癌（Merkel cell carcinoma，MCC）是一种罕见的皮肤神经内分泌癌，往往表现为局部复发和转移。通常，MCC 与多瘤病毒（Merkel cell polyomavirus，MCPyV）相关，细胞角蛋白 20（cytokeratin 20，CK20）阳性。然而，人们对这种肿瘤及其起源知之甚少。在这里，我们旨在确定 MCC 的发育起源，并确定预后临床病理因素。初步检查显示，CK20 和 MCPyV 表达（CK20+，MCPyV+（60%）；CK20+，MCPyV-（10%）；CK20-，MCPyV-（30%））并不影响总生存率。对包含整个外显子的 FFPE 标本进行 RB1 基因测序，所有 RB1 基因突变阳性病例均显示阳性区域淋巴结和/或远处转移（8/8 例，100%），而 RB1 基因突变阴性病例的转移频率统计学上显著降低（10/16 例，62%，P=0.033）。免疫组化也证实了这一结果，RB1 改变、整个外显子测序或免疫组化均与转移相关（P=0.007）。RB1 改变可用于评估 MCC 的侵袭性临床病程。
