Frequent EGFR expression/EGFR amplification and lack of activating mutation in testicular choriocarcinoma
Frequent EGFR expression/EGFR amplification and lack of activating mutation in testicular choriocarcinoma
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DOI：
10.1111/pin.12905
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发表时间：
2020-01-29
影响因子：
2.2
通讯作者：
Tsuda, Hitoshi
中科院分区：
文献类型：
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作者：
Miyai, Kosuke;Ito, Keiichi;Tsuda, Hitoshi
绒毛膜癌（CC）是成人睾丸生殖细胞瘤（TGCT）中最罕见但最具侵袭性的组织学成分。尽管我们之前报道了表皮生长因子受体（EGFR）改变在CC进展中的假定作用，但对EGFR激酶激活突变状态知之甚少，该状态预测了对EGFR酪氨酸激酶抑制剂的反应。在本研究中，我们对12例混合tgct与CC成分进行了临床病理回顾。通过免疫组织化学、荧光原位杂交和直接测序分别研究了这些CC成分中EGFR的表达、EGFR拷贝数的改变和EGFR的功能突变。12例患者中有4例（33%）表现出主要的CC成分（bbb50 %），所有患者均在62个月内死亡。在12种CC组分中，EGFR过表达、EGFR拷贝数增加和EGFR扩增分别为12（100%）、10（83%）和9（75%）。所有病例均未显示编码EGFR酪氨酸激酶结构域的外显子18至24发生突变。这些结果证实了EGFR在睾丸cc肿瘤侵袭性中的重要作用，并可能提示其对常规抗EGFR治疗的先天抗性。
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.