Angiogenesis in primary colorectal cancer and matched metastatic tissues: Biological and clinical implications for anti-angiogenic therapies

Lei Yin; Jianning Li; Dejian Ma; Donghua Li; Yanlai Sun

doi:10.3892/ol.2020.11450

Angiogenesis in primary colorectal cancer and matched metastatic tissues: Biological and clinical implications for anti-angiogenic therapies

Oncol Lett. 2020 May;19(5):3558-3566. doi: 10.3892/ol.2020.11450. Epub 2020 Mar 6.

Authors

Lei Yin¹, Jianning Li², Dejian Ma^{3

4}, Donghua Li⁵, Yanlai Sun⁴

Affiliations

¹ Department of Gastrointestinal Surgery, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, Zhejiang 313000, P.R. China.
² The Central Sterile Supply Department, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China.
³ School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
⁴ Department of Gastrointestinal Cancer Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China.
⁵ Department of Radiotherapy, Yuncheng People's Hospital, Yuncheng, Shandong 274700, P.R. China.

Abstract

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.

Keywords: colorectal carcinoma; hypoxia-inducible factor 1-α; immunohistochemistry; metastasis; microvascular density; vascular endothelial growth factor.