Yin Lei, Li Jianning, Ma Dejian, Li Donghua, Sun Yanlai
Department of Gastrointestinal Surgery, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, Zhejiang 313000, P.R. China.
The Central Sterile Supply Department, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China.
Oncol Lett. 2020 May;19(5):3558-3566. doi: 10.3892/ol.2020.11450. Epub 2020 Mar 6.
Metastasis remains a notable issue in patients with newly diagnosed colorectal carcinomas (CRC). Although anti-angiogenic therapies target metastatic diseases, hypoxia-inducible factor-1 α (HIF-1α) and vascular endothelial growth factor (VEGF) status are routinely evaluated in primary tumors as metastatic sites are infrequently biopsied. The present study aimed to investigate the expression and significance of HIF-1α, VEGF and microvascular density (MVD) in primary tumors and corresponding metastatic CRC tissues. HIF-1α, VEGF and CD34 status were analyzed via immunohistochemistry analysis in 46 patients who underwent surgical resection of primary CRC (35 colon and 11 rectum) and matched metastases (lymph node and liver metastases) in Shandong Cancer Hospital. The association between selected biomarker status and clinicopathological characteristics was analyzed, and expression levels in primary tumors and corresponding metastases were compared. A total of 46 paired colorectal primary tumor and synchronous metastases samples were acquired for analysis using a standardized HIF-1α, VEGF and CD34 immunohistochemical procedure. The results demonstrated that the positive rates of HIF-1α and VEGF in primary CRC were 70 and 73.9%, respectively. HIF-1α (60.9%) and VEGF (58.7%) expression decreased in the lymph metastatic samples compared with primary CRC. Conversely, the level of MVD in primary tumors was significantly higher compared with metastatic tumors. No significant differences were demonstrated between HIF-1α and VEGF expression and the different clinicopathological features in primary CRC and corresponding metastases. Primary carcinomas and matched metastatic tissues demonstrated a moderate level of consistent immunoreactivity for HIF-1α and VEGF. HIF-1α, VEGF and CD34 were expressed in both primary tumors and corresponding metastases of CRC, suggesting that they may be involved in the development of metastasis. HIF-1α and VEGF expression in primary sites was consistent with that observed in metastases; however, it varied from that exhibited in MVD. The current analysis will improve the current understanding of the metastasis models and provide further evidence for evaluating the response to HIF-1α and VEGF inhibitors.
转移仍是新诊断的结直肠癌（CRC）患者的一个显著问题。尽管抗血管生成疗法针对转移性疾病，但由于很少对转移部位进行活检，因此通常在原发性肿瘤中评估缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）的状态。本研究旨在探讨HIF-1α、VEGF和微血管密度（MVD）在原发性肿瘤及相应转移性CRC组织中的表达及意义。通过免疫组织化学分析，对山东省肿瘤医院46例行原发性CRC手术切除（35例结肠癌和11例直肠癌）及匹配转移灶（淋巴结和肝转移）的患者的HIF-1α、VEGF和CD34状态进行了分析。分析了所选生物标志物状态与临床病理特征之间的关联，并比较了原发性肿瘤和相应转移灶中的表达水平。使用标准化的HIF-1α、VEGF和CD34免疫组织化学程序，共获取了46对结直肠癌原发性肿瘤和同步转移样本进行分析。结果表明，原发性CRC中HIF-1α和VEGF的阳性率分别为70%和73.9%。与原发性CRC相比，淋巴转移样本中HIF-1α（60.9%）和VEGF（58.7%）的表达降低。相反，原发性肿瘤中的MVD水平明显高于转移性肿瘤。原发性CRC及其相应转移灶中HIF-1α和VEGF的表达与不同临床病理特征之间未显示出显著差异。原发性癌和匹配的转移组织对HIF-1α和VEGF表现出中等程度的一致免疫反应性。HIF-1α、VEGF和CD34在CRC的原发性肿瘤和相应转移灶中均有表达，表明它们可能参与了转移的发生。原发性部位的HIF-1α和VEGF表达与转移灶中观察到的一致；然而，它与MVD中表现出的不同。当前的分析将改善对转移模型的当前理解，并为评估对HIF-1α和VEGF抑制剂的反应提供进一步的证据。
