Department of Basic Pathology, National Defense Medical College, Saitama, Japan.
Department of Laboratory Medicine, National Defense Medical College, Saitama, Japan.
Pathol Int. 2020 May;70(5):262-269. doi: 10.1111/pin.12905. Epub 2020 Jan 29.
Choriocarcinoma (CC) is the rarest but most aggressive histological component of adult testicular germ cell tumor (TGCT). Although we previously reported a putative role of epidermal growth factor receptor (EGFR) alterations in the progression of CC, little is known about the kinase-activating mutation status of EGFR, which predicts the response to EGFR-tyrosine kinase inhibitors. In this study, we clinicopathologically reviewed a total of 12 cases of mixed TGCTs with CC components. Immunohistochemistry, fluorescence in situ hybridization, and direct sequencing was performed to investigate EGFR expression, EGFR copy number alterations, and functional mutation of EGFR in these CC components, respectively. Four (33%) of 12 cases exhibited predominant CC components (>50%), and all these patients died due to disease within 62 months. Overexpression of EGFR, higher copy number of EGFR, and amplification of EGFR was observed in 12 (100%), 10 (83%), and 9 (75%) of 12 CC components, respectively. None of the cases showed any mutational events in exons 18 to 24, which encode the tyrosine kinase domain of EGFR. These results confirm an important role of EGFR in the tumor aggressiveness of testicular CCs and may suggest its possible innate resistance against conventional anti-EGFR therapies.
绒癌（CC）是成人睾丸生殖细胞肿瘤（TGCT）中最罕见但侵袭性最强的组织学成分。尽管我们之前报道了表皮生长因子受体（EGFR）改变在 CC 进展中的作用，但对于预测 EGFR 酪氨酸激酶抑制剂反应的 EGFR 激酶激活突变状态知之甚少。在这项研究中，我们对总共 12 例具有 CC 成分的混合 TGCT 进行了临床病理复习。进行了免疫组织化学、荧光原位杂交和直接测序，以分别研究这些 CC 成分中 EGFR 的表达、EGFR 拷贝数改变和 EGFR 的功能突变。在 12 例病例中，有 4 例（33%）以主要 CC 成分为主（>50%），所有这些患者均因疾病在 62 个月内死亡。在 12 例 CC 成分中，EGFR 的过度表达、EGFR 拷贝数的增加和 EGFR 的扩增分别为 12 例（100%）、10 例（83%）和 9 例（75%）。在 18 至 24 外显子编码 EGFR 酪氨酸激酶结构域的情况下，没有任何病例显示出任何突变事件。这些结果证实了 EGFR 在睾丸 CC 肿瘤侵袭性中的重要作用，并可能提示其对传统抗 EGFR 治疗的固有耐药性。
