Epidermal growth factor receptor variant III (EGFRvIII, the deletion of exons 2–7) is a recurrent intragenicEGFR::EGFR.E1E8 fusion that occurs in high-grade gliomas. The presence of EGFRvIII in other solid tumors has not been well characterized. We retrospectively reviewed advanced malignant solid tumor cases tested by a custom hybrid capture 610-gene next-generation sequencing platform from 2021 to 2022. EGFRvIII was identified in 17 of 4331 (0.4%) cases, including 16 of 238 (7%) brain tumors and 1/301 (0.3%) breast tumors. EGFRvIII-positive brain tumors were all glioblastoma IDH-wildtype, most with concurrentTERTpromoter mutation (14 of 16),EGFRamplification (13 of 16), andEGFRmutation (8 of 16). The only EGFRvIII-positive breast lesion was a sarcomatoid neoplasm in a young female patient. A separate breast case tested outside our institution with reported EGFRvIII was noted in a young female patient with a malignant phyllodes tumor with stromal overgrowth. Microscopically, both EGFRvIII-positive breast tumors showed high-grade sarcomatoid morphology with brisk mitotic activity. In summary, EGFRvIII is rare, occurring primarily in glioblastoma and rarely in breast sarcomatoid neoplasm, with no instances identified in other tumor types in our series. This select group of patients may benefit from chemotherapy and/or targeted anti-EGFR therapy.
表皮生长因子受体III型变异体（EGFRvIII，即外显子2-7缺失）是一种在高级别胶质瘤中反复出现的EGFR::EGFR.E1E8基因内融合。EGFRvIII在其他实体瘤中的存在情况尚未得到充分描述。我们回顾性分析了2021年至2022年间通过定制的610基因杂交捕获新一代测序平台检测的晚期恶性实体瘤病例。在4331例病例中，共发现17例（0.4%）存在EGFRvIII，包括238例脑肿瘤中的16例（7%）和301例乳腺肿瘤中的1例（0.3%）。EGFRvIII阳性的脑肿瘤均为IDH野生型胶质母细胞瘤，其中多数同时伴有TERT启动子突变（16例中14例）、EGFR扩增（16例中13例）及EGFR突变（16例中8例）。唯一一例EGFRvIII阳性的乳腺病变为一位年轻女性患者的肉瘤样肿瘤。另有一例在本机构外检测并报告为EGFRvIII阳性的乳腺病例，为一位患有伴间质过度生长的恶性叶状肿瘤的年轻女性患者。镜下观察显示，这两例EGFRvIII阳性乳腺肿瘤均呈现高级别肉瘤样形态，伴有活跃的核分裂活动。总之，EGFRvIII较为罕见，主要见于胶质母细胞瘤，偶见于乳腺肉瘤样肿瘤，本系列研究中未在其他肿瘤类型中发现该变异。这一特定患者群体可能从化疗和/或靶向抗EGFR治疗中获益。
IntragenicEGFR::EGFR.E1E8 Fusion (EGFRvIII) in 4331 Solid Tumors
肿瘤(癌症)患者之家