Ganti Ramapriya, Skapek Stephen X, Zhang Jie, Fuller Christine E, Wu Jianrong, Billups Catherine A, Breitfeld Philip P, Dalton James D, Meyer William H, Khoury Joseph D
Department of Pathology and Laboratory Medicine, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Mod Pathol. 2006 Sep;19(9):1213-20. doi: 10.1038/modpathol.3800636. Epub 2006 May 26.
Both epidermal growth factor receptor (EGFR) and ErbB-2 play an important role in cancer biology and constitute promising molecular targets of therapy. EGFR and ErbB-2 expression has been observed in rhabdomyosarcoma cell lines but not analyzed systematically in rhabdomyosarcoma tumors. Tissue microarray sections representing 66 rhabdomyosarcoma tumors (34 embryonal rhabdomyosarcoma, 32 alveolar rhabdomyosarcoma) were surveyed by immunohistochemistry using antibodies specific for EGFR and ErbB-2. Immunostains were assessed for intensity (0: no immunostaining; 1: weak; 2: moderate; 3: strong) and percentage of at least 500 neoplastic cells exhibiting membranous or membranous and cytoplasmic immunostaining. EGFR and ErbB-2 expression was considered positive if the product of intensity and percentage was greater than 10. Patients had a median age of 5.7 years (range 8 months-19.1 years), and of 65/66 patients, 38 were males and 27 were females. Expression of ErbB-2 was identified in 22/66 (33%) cases and tended to be more frequent in the alveolar subtype (13/32, 41%, vs 9/34, 26%, P=0.30). Expression of EGFR was identified in 31/66 (47%) cases and correlated with the embryonal subtype (26/34, 76%, vs 5/32, 16%, P<0.0001) independent of stage, age, and gender. Coexpression of EGFR and ErbB-2 was identified in eight tumors, of which six were embryonal rhabdomyosarcoma. None of the cases exhibited EGFR or ErbB-2 gene amplification, as assessed using fluorescence in situ hybridization. Furthermore, analysis of 11 additional rhabdomyosarcoma tumors (six alveolar; five embryonal) revealed no evidence of mutations in EGFR exons 18, 19, 20, and 21. In summary, expression of EGFR and/or ErbB-2 is detected in a sizeable subset of rhabdomyosarcoma tumors without evidence of EGFR or ErbB-2 amplification or mutations in the EGFR tyrosine kinase domain. Notably, expression of EGFR correlates with the embryonal subtype, which is also more likely to coexpress EGFR and ErbB-2.
表皮生长因子受体（EGFR）和ErbB-2在癌症生物学中均发挥重要作用，是很有前景的治疗分子靶点。在横纹肌肉瘤细胞系中已观察到EGFR和ErbB-2的表达，但尚未在横纹肌肉瘤肿瘤中进行系统分析。使用针对EGFR和ErbB-2的特异性抗体，通过免疫组织化学对代表66例横纹肌肉瘤肿瘤（34例胚胎性横纹肌肉瘤，32例肺泡状横纹肌肉瘤）的组织微阵列切片进行检测。评估免疫染色的强度（0：无免疫染色；1：弱；2：中度；3：强）以及至少500个显示膜性或膜性及胞质免疫染色的肿瘤细胞的百分比。如果强度与百分比的乘积大于10，则认为EGFR和ErbB-2表达为阳性。患者的中位年龄为5.7岁（范围8个月至19.1岁），66例患者中的65例，男性38例，女性27例。在66例中的22例（33%）病例中检测到ErbB-2的表达，在肺泡亚型中更常见（13/32，41%，对比9/34，26%，P = 0.30）。在66例中的31例（47%）病例中检测到EGFR的表达，且与胚胎亚型相关（26/34，76%，对比5/32，16%，P<0.0001），与分期、年龄和性别无关。在8个肿瘤中检测到EGFR和ErbB-2的共表达，其中6个为胚胎性横纹肌肉瘤。使用荧光原位杂交评估，所有病例均未显示EGFR或ErbB-2基因扩增。此外，对另外11例横纹肌肉瘤肿瘤（6例肺泡状；5例胚胎性）的分析显示，EGFR外显子18、19、20和21没有突变证据。总之，在相当一部分横纹肌肉瘤肿瘤中检测到EGFR和/或ErbB-2的表达，且没有EGFR或ErbB-2扩增或EGFR酪氨酸激酶结构域突变的证据。值得注意的是，EGFR的表达与胚胎亚型相关，胚胎亚型也更可能共表达EGFR和ErbB-2。
