Ionescu Diana N, Sasatomi Elizaburo, Cieply Kathleen, Nola Marin, Dacic Sanja
Division of Anatomic Pathology, Department of Pathology, University of Pittsburgh Medical Center, Presbyterian University Hospital, Pittsburgh, Pennsylvania, USA.
Cancer. 2005 Feb 1;103(3):630-6. doi: 10.1002/cncr.20811.
Epidermal growth factor receptor (EGFR) overexpression and amplification are important prognostic factors in many solid tumors and anti-EGFR antibody-based therapy is now available as a promising therapeutic modality. There is little information in the literature regarding the biologic role of EGFR in thymomas that are characterized by variable clinical presentations, histologic heterogeneity, and unpredictable behavior.
Protein expression and gene amplification of EGFR were investigated in 32 thymomas (9 World Health Organization [WHO] type A, 5 type AB, 7 type B2, 7 type B3, 4 type C) using immunohistochemistry and fluorescence in situ hybridization (FISH). FISH analysis included assessment of the average number of copies of the EGFR gene per cell, the average ratio of the EGFR gene to chromosome 7 copy numbers, and ploidy.
The results of FISH analysis showed statistically significant correlation with WHO histologic type, invasion, advanced clinical stage, but not with tumor size and outcome. Thymomas associated with myasthenia gravis more frequently showed hyperploidy when compared with sporadic tumors, but there was no difference in EGFR gene amplification. EGFR protein expression assessed by immunohistochemistry did not correlate with any studied clinicopathologic variables. There was poor correlation between the protein expression and gene amplification, only 7 of 23 specimens (30%).
The potential role of EGFR in the pathogenesis of advanced-stage thymomas indicated that evolving anti-EGFR antibody therapy may be considered as a treatment option.
表皮生长因子受体（EGFR）的过表达和扩增是许多实体瘤重要的预后因素，基于抗EGFR抗体的治疗目前是一种很有前景的治疗方式。关于EGFR在胸腺瘤中的生物学作用，文献中报道较少，胸腺瘤具有临床表现多样、组织学异质性及行为不可预测等特点。
采用免疫组织化学和荧光原位杂交（FISH）技术，对32例胸腺瘤（9例世界卫生组织[WHO] A型、5例AB型、7例B2型、7例B3型、4例C型）进行EGFR蛋白表达及基因扩增研究。FISH分析包括评估每个细胞EGFR基因的平均拷贝数、EGFR基因与7号染色体拷贝数的平均比值及倍性。
FISH分析结果显示，与WHO组织学类型、侵袭、临床晚期显著相关，但与肿瘤大小及预后无关。与散发性胸腺瘤相比，合并重症肌无力的胸腺瘤更常表现为超倍体，但EGFR基因扩增无差异。免疫组织化学评估的EGFR蛋白表达与任何研究的临床病理变量均无相关性。蛋白表达与基因扩增之间相关性较差，23个标本中仅7个（30%）。
EGFR在晚期胸腺瘤发病机制中的潜在作用表明，正在发展的抗EGFR抗体治疗可被视为一种治疗选择。
