Correlation of EPHA2 overexpression with high microvessel count in human primary colorectal cancer
Correlation of EPHA2 overexpression with high microvessel count in human primary colorectal cancer
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DOI：
10.1111/j.1349-7006.2004.tb03194.x
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发表时间：
2004-02-01
期刊：
影响因子：
5.7
通讯作者：
Sugimura, H
中科院分区：
文献类型：
--
作者：
Kataoka, H;Igarashi, H;Sugimura, H
有证据表明，促红细胞生成素生成的肝细胞 (EPH) 受体酪氨酸激酶 (RTK) 及其肝配蛋白 (EFN) 配体参与人类致癌作用。其中两种的表达，即 EFNA1 配体及其受体 EPHA2，已被认为有助于肿瘤诱导的新血管形成。通过半定量 RT-PCR 检查结直肠癌中 EPHA2 及其配体 EFNA1 的表达，并对 EPHA2 和 CD34 进行双重免疫染色。对肿瘤中的微血管进行计数。还对 25 例伴有局灶性癌的腺瘤进行双染以进行比较。与同一标本中相应的正常组织相比，在肿瘤组织中发现了 EPHA2 和 EFNA1 过表达的趋势[分别为 22/37 (59.5%) 和 25/37 (67.5%)；对于 EPHA2，P=0.100；对于 EFNA1，P=0.009]。 EPHA2 和 EFNA1 的过表达在早期比在晚期更常见 [EPHA2，15/21 (71.4%) vs. 7/16 (43.8%)，P=0.007； EFNA1，15/21 (71.4%) 与 10/16 (62.5%)，P=0.007]。 EPHA2 和 EFNA1 在较小肿瘤（小于 5 cm）中比在较大肿瘤中更频繁地过表达 [EPHA2，15/21 (71.4%) vs. 7/16 (43.8%)，P=0.017； EFNA1，16/21 (76.2%) 与 8/16 (50%)，P=0.001]。直径小于 5 cm 且处于 I 期和 11 期的肿瘤明显更有可能过表达 EPHA2 和 EFNA1（EPHA2 的 P=0.001，EFNA1 的 P=0.001）。 CD34免疫染色后的微血管计数（MVC）与EPHA2的过表达显着相关（r=0.343，P=0.037）。表达 EPHA2 的局灶性癌症也围绕着局灶性癌症的腺瘤中的微血管。这些发现表明 EPHA2 参与结肠癌发生，主要是在 I 期和 II 期，并且可能是通过其对微血管诱导的影响。
Evidence suggests that the erythropoietin-producing hepatocellular (EPH) receptor tyrosine kinases (RTKs) and their ephrin (EFN) ligands are involved in human carcinogenesis. Expression of two of them, EFNA1 ligand and its receptor, EPHA2, has been proposed to contribute to tumor-induced neovascularization. Colorectal cancers were examined for expressions of EPHA2 and its ligand EFNA1 by semi-quantitative RT-PCR, and double-immunostained for EPHA2 and CD34. Microvessels in the tumors were counted. Double-staining was also performed in 25 cases of adenoma with focal cancer for comparison. Trends of overexpression of both EPHA2 and EFNA1 was found in tumor tissue compared to the corresponding normal tissue in the same specimen [22/37 (59.5%) and 25/37 (67.5%), respectively; P=0.100 for EPHA2 and P=0.009 for EFNA1]. Overexpression of EPHA2 and EFNA1 was noted more frequently in the early stage than in the late stage [EPHA2, 15/21 (71.4%) vs. 7/16 (43.8%), P=0.007; EFNA1, 15/21 (71.4%) vs. 10/16 (62.5%), P=0.007]. Both EPHA2 and EFNA1 were more frequently overexpressed in smaller tumors (less than 5 cm) than in larger tumors [EPHA2, 15/21 (71.4%) vs. 7/16 (43.8%), P=0.017; EFNA1, 16/21 (76.2%) vs. 8/16 (50%), P=0.001]. Tumors less than 5 cm in diameter and in stages I and 11 were significantly more likely to overexpress EPHA2 and EFNA1 (P=0.001 for EPHA2, P=0.001 for EFNA1). Microvessel counts (MVCs) after immunostaining for CD34 were significantly correlated (r=0.343, P=0.037) with overexpression of EPHA2. EPHA2-expressing focal cancer also surrounded microvessels in adenomas with focal cancers. These findings suggest an involvement of EPHA2 in colon carcinogenesis, mainly in stages I and II, and probably through their effect on microvessel-induction.