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成年睾丸生殖细胞肿瘤中表皮生长因子受体的蛋白过表达和基因扩增:在肿瘤进展中的潜在作用。

Protein overexpression and gene amplification of epidermal growth factor receptor in adult testicular germ cell tumors: potential role in tumor progression.

机构信息

Department of Basic Pathology, Tokorozawa, Saitama, Japan.

出版信息

Cancer Sci. 2010 Sep;101(9):1970-6. doi: 10.1111/j.1349-7006.2010.01638.x.

DOI:10.1111/j.1349-7006.2010.01638.x
PMID:20608935
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11159324/
Abstract

Little is known about the pathologic significance of epidermal growth factor receptor (EGFR) expression in malignant testicular germ cell tumors (TGCTs) in adults. From the primary tumor sites of a cohort of 110 TGCT cases, we obtained 209 histologically distinct components: 53 intratubular germ cell neoplasia unclassified (IGCNU) lesions, 83 seminomas (66 pure-form seminomas and 17 seminoma components in the mixed-form with nonseminomatous TGCTs), 27 embryonal carcinomas, eight choriocarcinomas, 18 yolk sac tumors, and 20 immature teratomas. Samples were analyzed for expression of EGFR protein and EGFR gene amplification by immunohistochemistry and fluorescence in situ hybridization (FISH), respectively. Overexpression of the EGFR protein was detected in 28% of seminomas (27% in the pure-form and 29% in the mixed-form), 11% of embryonal carcinomas, 88% of choriocarcinomas, 44% of yolk sac tumors, and none of the IGCNU lesions or immature teratomas. A higher copy number (≥4 copies per cell) and amplification of the EGFR gene were detected in 20% and 10% of seminomas, 13% and 0% of embryonal carcinomas, 71% and 60% of choriocarcinomas, 15% and 8% of yolk sac tumors, and none of the IGCNU lesions or immature teratomas, respectively. Both higher copy number and amplification of the EGFR gene were positively correlated with immunohistochemical overexpression of EGFR protein (each P < 0.0001). These results suggest that overexpression of EGFR protein and increased copy number or amplification of the EGFR gene occur relatively frequently in primary TGCTs, and may play roles in the formation of invasive cancer and in the progression, especially morphological evolution, of tumors.

摘要

关于表皮生长因子受体(EGFR)在成人恶性睾丸生殖细胞肿瘤(TGCT)中的表达的病理意义知之甚少。我们从 110 例 TGCT 病例的原发性肿瘤部位获得了 209 个组织学上不同的成分:53 个未分类的管状内生殖细胞肿瘤(IGCNU)病变,83 个精原细胞瘤(66 个纯形式的精原细胞瘤和 17 个混合形式的精原细胞瘤成分与非精原细胞瘤 TGCT),27 个胚胎癌,8 个绒毛膜癌,18 个卵黄囊瘤和 20 个未成熟畸胎瘤。通过免疫组织化学和荧光原位杂交(FISH)分别分析 EGFR 蛋白表达和 EGFR 基因扩增。EGFR 蛋白过表达在 28%的精原细胞瘤中检测到(纯形式为 27%,混合形式为 29%),11%的胚胎癌,88%的绒毛膜癌,44%的卵黄囊瘤,IGCNU 病变或未成熟畸胎瘤均未检测到。在 20%的精原细胞瘤和 10%的胚胎癌中检测到 EGFR 基因的更高拷贝数(≥4 个拷贝/细胞)和扩增,在 13%和 0%的胚胎癌中,71%和 60%的绒毛膜癌,15%和 8%的卵黄囊瘤,IGCNU 病变或未成熟畸胎瘤均未检测到。EGFR 基因的更高拷贝数和扩增均与 EGFR 蛋白的免疫组织化学过表达呈正相关(均 P<0.0001)。这些结果表明,EGFR 蛋白的过表达和 EGFR 基因的拷贝数增加或扩增在原发性 TGCT 中相对频繁发生,并且可能在侵袭性癌症的形成以及肿瘤的进展,特别是形态演变中发挥作用。

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