埃及常见原发性肝癌中血管内皮生长因子和细胞周期蛋白 D1/EGFR 的表达:一项免疫组化研究

D. Sweed, Shaymaa Sabry El Gammal, S. Kilany, S. Abdelsattar, Sara Mohamed Abd Elhamed
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摘要

背景:最常见的原发性恶性肝肿瘤是肝细胞癌(HCC)和胆管癌(CCA)。无法手术/晚期或复发患者的治疗方案具有挑战性。细胞周期蛋白 D1、表皮生长因子(EGFR)和血管内皮生长因子(VEGR)是常见的致癌蛋白,是各种癌症的潜在治疗靶点。它们被认为与 HCC 和 CCA 的发展有关。本研究旨在评估细胞周期蛋白 D1、表皮生长因子受体和血管内皮生长因子在埃及 HCC 和 CCA 患者中的致癌功能表达。这有助于验证它们的治疗潜力。材料和方法:肿瘤病例选自 82 例原发性肝癌,其中 58 例来自 HCC,24 例来自 CCA,而非肿瘤邻近肝脏病例 51 例,正常肝组织 18 例。对细胞周期蛋白 D1、表皮生长因子受体(EGFR)和血管内皮生长因子受体(VEGR)进行免疫组化研究。结果显示与对照组相比,细胞周期蛋白 D1、表皮生长因子受体(EGFR)和血管内皮生长因子(VEGF)在 HCC 和 CCA 中过表达(P < 0.001)。细胞周期蛋白 D1 与 HCC 的分化程度和早期病理分期有关(分别为 p = 0.016 和 p = 0.042)。分化良好的分级显示血管内皮生长因子水平明显更高(p = 0.04)。然而,在CCA组中,表皮生长因子受体(EGFR)与肿瘤大小密切相关(p = 0.047)。与肝硬化后发生的 HCC 相比,非肝硬化发生的 HCC 表皮生长因子受体和血管内皮生长因子表达过高 ( p = 0.003 和 p = 0.014)。结论细胞周期蛋白 D1、表皮生长因子受体(EGFR)和血管内皮生长因子(VEGF)在 HCC 和 CCA 中均显著过表达。表皮生长因子受体(EGFR)和血管内皮生长因子(VEGF)可能在非肝硬化的 HCC 发病过程中发挥致癌作用。此外,细胞周期蛋白 D1 和血管内皮生长因子在 HCC 中可能起到良好的预后作用,但表皮生长因子受体在 CCA 中可能起到不良的预后作用。
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The expression of VEGF and cyclin D1/EGFR in common primary liver carcinomas in Egypt: an immunohistochemical study
Background: The most common types of primary malignant liver tumours are hepato-cellular carcinoma (HCC) and cholangiocarcinoma (CCA). Treatment options for patients who are inoperable/advanced, or recurring are challenging. Cyclin D1, epidermal growth factor (EGFR) and vascular endothelial growth factor (VEGR) are common carcinogenic proteins that have potential therapeutic targets in various cancers. They have been implicated in the development of HCC and CCA. In this study, we aimed to evaluate the oncogenic function expression of cyclin D1, EGFR and VEGF in HCC and CCA of Egyptian patients. This could help to validate their therapeutic potential. Material and methods: Tumour cases were selected from 82 cases of primary liver carcinomas, with 58 cases being from HCC and 24 cases from CCA compared to 51 non-tumour adjacent liver cases and 18 from normal liver tissue. The immunohistochemical study of cyclin D1, EGFR and VEGR was conducted. Results: Cyclin D1, EGFR and VEGF are overexpressed in HCC and CCA as compared to the control group ( p < 0.001). Cyclin D1 was related to well-differentiated grade and early pathologic stage in HCC ( p = 0.016 and p = 0.042, respectively). The well-differentiated grade showed significantly higher VEGF levels ( p = 0.04). In the CCA group, however, EGFR was strongly related to high tumour size ( p = 0.047). EGFR and VEGF were over-expressed in HCC raised in the non-cirrhotic liver compared to those developed in post-hepatitic liver cirrhosis ( p = 0.003 and p = 0.014). Conclusion: Cyclin D1, EGFR and VEGF shared significant overexpression in HCC and CCA. EGFR and VEGF may play an oncogenic function in the development of HCC in non-cirrhotic liver. Furthermore, cyclin D1 and VEGF may play a good prognostic function in HCC, but EGFR may play a bad prognostic role in CCA.
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