Cargando…

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

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 meta...

Descripción completa

Detalles Bibliográficos
Autores principales: Yin, Lei, Li, Jianning, Ma, Dejian, Li, Donghua, Sun, Yanlai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115125/
https://www.ncbi.nlm.nih.gov/pubmed/32269630
http://dx.doi.org/10.3892/ol.2020.11450
_version_ 1783514034915508224
author Yin, Lei
Li, Jianning
Ma, Dejian
Li, Donghua
Sun, Yanlai
author_facet Yin, Lei
Li, Jianning
Ma, Dejian
Li, Donghua
Sun, Yanlai
author_sort Yin, Lei
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7115125
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-71151252020-04-08 Angiogenesis in primary colorectal cancer and matched metastatic tissues: Biological and clinical implications for anti-angiogenic therapies Yin, Lei Li, Jianning Ma, Dejian Li, Donghua Sun, Yanlai Oncol Lett Articles 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. D.A. Spandidos 2020-05 2020-03-06 /pmc/articles/PMC7115125/ /pubmed/32269630 http://dx.doi.org/10.3892/ol.2020.11450 Text en Copyright: © Yin et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Yin, Lei
Li, Jianning
Ma, Dejian
Li, Donghua
Sun, Yanlai
Angiogenesis in primary colorectal cancer and matched metastatic tissues: Biological and clinical implications for anti-angiogenic therapies
title Angiogenesis in primary colorectal cancer and matched metastatic tissues: Biological and clinical implications for anti-angiogenic therapies
title_full Angiogenesis in primary colorectal cancer and matched metastatic tissues: Biological and clinical implications for anti-angiogenic therapies
title_fullStr Angiogenesis in primary colorectal cancer and matched metastatic tissues: Biological and clinical implications for anti-angiogenic therapies
title_full_unstemmed Angiogenesis in primary colorectal cancer and matched metastatic tissues: Biological and clinical implications for anti-angiogenic therapies
title_short Angiogenesis in primary colorectal cancer and matched metastatic tissues: Biological and clinical implications for anti-angiogenic therapies
title_sort angiogenesis in primary colorectal cancer and matched metastatic tissues: biological and clinical implications for anti-angiogenic therapies
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115125/
https://www.ncbi.nlm.nih.gov/pubmed/32269630
http://dx.doi.org/10.3892/ol.2020.11450
work_keys_str_mv AT yinlei angiogenesisinprimarycolorectalcancerandmatchedmetastatictissuesbiologicalandclinicalimplicationsforantiangiogenictherapies
AT lijianning angiogenesisinprimarycolorectalcancerandmatchedmetastatictissuesbiologicalandclinicalimplicationsforantiangiogenictherapies
AT madejian angiogenesisinprimarycolorectalcancerandmatchedmetastatictissuesbiologicalandclinicalimplicationsforantiangiogenictherapies
AT lidonghua angiogenesisinprimarycolorectalcancerandmatchedmetastatictissuesbiologicalandclinicalimplicationsforantiangiogenictherapies
AT sunyanlai angiogenesisinprimarycolorectalcancerandmatchedmetastatictissuesbiologicalandclinicalimplicationsforantiangiogenictherapies