Sato Osamu, Wada Takuro, Kawai Akira, Yamaguchi Umio, Makimoto Atsushi, Kokai Yasuo, Yamashita Toshihiko, Chuman Hirokazu, Beppu Yasuo, Tani Yoichi, Hasegawa Tadashi
Department of Orthopaedic Surgery, Sapporo Medical University, Sapporo, Japan.
Cancer. 2005 May 1;103(9):1881-90. doi: 10.1002/cncr.20986.
Little is known about the expression of receptor tyrosine kinases in adult soft tissue sarcomas (STS). In the current study, the authors analyzed the expression of epidermal growth factor receptor (EGFR), ERBB2, and KIT in 281 patients with STS who were treated in a single institution. Verification of the presence of an association with prognosis was performed.
The current study included 281 adult patients with STS of the extremity and trunk who were diagnosed and treated in the National Cancer Center, Tokyo. Expression was assessed using immunohistochemical stains for EGFR, ERBB2, and KIT on formalin-fixed, paraffin-embedded tissue sections by standard avidin-biotin peroxidase complex technique and EGFR detection system.
Positive staining of EGFR was observed in 168 of 281 (60%) patients. Positive staining was common in pleomorphic malignant fibrous histiocytomas (89%), myxofibrosarcomas (89%), synovial sarcomas (76%), malignant peripheral nerve sheath tumors (89%), and leiomyosarcomas (73%). It was less common in well differentiated liposarcomas (38%), fibrosarcomas (36%), and myxoid liposarcomas (6%). In contrast, positive staining of ERBB2 and KIT was very limited. Increased levels of EGFR were significantly associated with a decreased probability of overall survival (P = 0.01), although by univariate analysis; probability of overall survival at 5 years was 64% in patients with increased levels of EGFR and 79% in patients without such overexpression. The overexpression of EGFR was significantly associated with histologic grade (P < 0.001). Moreover, stratified log-rank test revealed that there is an interrelation between EGFR overexpression and histologic grade.
EGFR overexpression was found to be a negative prognostic factor of adult STS, which is strongly associated with histologic grade. STS patients with EGFR overexpression may benefit from treatment with currently available biospecific inhibitors for EGFR.
关于受体酪氨酸激酶在成人软组织肉瘤（STS）中的表达情况，人们了解甚少。在本研究中，作者分析了281例在单一机构接受治疗的STS患者中表皮生长因子受体（EGFR）、ERBB2和KIT的表达情况，并对其与预后的相关性进行了验证。
本研究纳入了281例在东京国立癌症中心诊断并接受治疗的成人肢体和躯干STS患者。通过标准抗生物素蛋白-生物素过氧化物酶复合物技术和EGFR检测系统，在福尔马林固定、石蜡包埋的组织切片上使用免疫组织化学染色评估EGFR、ERBB2和KIT的表达。
281例患者中有168例（60%）EGFR染色呈阳性。阳性染色在多形性恶性纤维组织细胞瘤（89%）、黏液纤维肉瘤（89%）、滑膜肉瘤（76%）、恶性外周神经鞘瘤（89%）和平滑肌肉瘤（73%）中较为常见。在高分化脂肪肉瘤（38%）、纤维肉瘤（36%）和黏液样脂肪肉瘤（6%）中则较少见。相比之下，ERBB2和KIT的阳性染色非常有限。尽管单因素分析显示，EGFR水平升高与总生存概率降低显著相关（P = 0.01）；EGFR水平升高的患者5年总生存概率为64%，未发生此类过表达的患者为79%。EGFR的过表达与组织学分级显著相关（P < 0.001）。此外，分层对数秩检验显示EGFR过表达与组织学分级之间存在相互关系。
EGFR过表达是成人STS的不良预后因素，与组织学分级密切相关。EGFR过表达的STS患者可能从目前可用的EGFR生物特异性抑制剂治疗中获益。
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