Predictive Significance of VEGF and HIF-1α Expression in Patients with Metastatic Colorectal Cancer Receiving Chemotherapy Combinations with Bevacizumab

Berk, Velı; Denız, Kemal; Bozkurt, Oktay; Özaslan, Ersin; Karaca, Halıt; İnanç, Mevlüde; Duran, Ayşe Ocak; Özkan, Metin

doi:10.7314/apjcp.2015.16.14.6149

Cited by 16 publications

(14 citation statements)

References 31 publications

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“…liver metastases tissues of 46 patients with mCRC were investigated and compared with the primary tumor. HIF-1α, VEGF and CD34 were positively expressed at both sites, indicating that they were closely associated with the occurrence and development of mCRC (25). Further research and analysis demonstrated no significant difference in the expression levels of HIF-1α and VEGF across different ages, sex, tumor sizes and degrees of histological differentiation.…”

Section: Discussionmentioning

confidence: 82%

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

Yin

et al. 2020

Oncol Lett

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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.

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Section: Discussionmentioning

confidence: 82%

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

Yin

et al. 2020

Oncol Lett

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“…However, the expression of VEGF as a prognostic factor has been debatable. Ochs et al [55] suggested that the overexpression of VEGF was associated with poorer survival, while Berk et al [56] observed an improved PFS and OS in patients with high VEGF expression. In this regard, antiangiogenic treatments deserve further research.…”

Section: Molecular Background Of Mucinous Colorectal Adenocarcinomamentioning

confidence: 99%

Mucinous colorectal adenocarcinoma: clinical pathology and treatment options

Luo

Cen

Ding

et al. 2019

Cancer Communications

208

216

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Mucinous colorectal adenocarcinoma is a distinct subtype of colorectal cancer (CRC) characterized by the presence of abundant extracellular mucin which accounts for at least 50% of the tumor volume. Mucinous colorectal adenocarcinoma is found in 10%–20% of CRC patients and occurs more commonly in female and younger patients. Moreover, mucinous colorectal adenocarcinoma is more frequently located in the proximal colon and diagnosed at an advanced stage. Based on its molecular context, mucinous colorectal adenocarcinoma is associated with the overexpression of mucin 2 (MUC2) and mucin 5AC (MUC5AC) proteins. At the same time, it shows higher mutation rates in the fundamental genes of the RAS/MAPK and PI3K/Akt/mTOR pathways. Mucinous colorectal adenocarcinoma also shows higher rates of microsatellite instability (MSI) than non-mucinous colorectal adenocarcinoma which might correlate it with Lynch syndrome and the CpG island methylator phenotype. The prognosis of mucinous colorectal adenocarcinoma as to non-mucinous colorectal adenocarcinoma is debatable. Further, the impaired responses of mucinous colorectal adenocarcinoma to palliative or adjuvant chemotherapy warrant more studies to be performed for a specialized treatment for these patients. In this review, we discuss the molecular background and histopathology of mucinous colorectal adenocarcinoma, and provide an update on its prognosis and therapeutics from recent literatures.

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“…It was investigated whether VEGF had predictive value in mCRC patients receiving bevacizumab; no significant difference was found. 21 CRC is the first malignancy where clear evidence was shown for the efficacy of anti-VEGF strategy in randomized trials. Recently, newly developed targeted therapies have led to significant improvements in the survival of metastatic CRC patients.…”

Section: Discussionmentioning

confidence: 99%

“…In a group with low expression of PDGF-BB, mOS was 21 months (95% CI [16][17][18][19][20][21][22][23][24][25][26], and in a group with high expression of PDGF-BB, mOS was 31 months (95% CI 5-57) (p ¼ 0.16).mOS was 26 months (Figure 2).…”

Section: Survival Analysis (Pfs Mos)mentioning

confidence: 99%

The prognostic importance of VEGF-A, PDGF-BB and c-MET in patients with metastatic colorectal cancer

İnanç

Sirakaya

Karaman

et al. 2020

J Oncol Pharm Pract

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Introduction: We aimed to assess the effect of VEGF-A, PDGF-BB, and c-Met expression levels on survival in patients with metastatic colorectal cancer receiving bevacizumab therapies. Patients and methods: A total of 105 patients diagnosed with metastatic colorectal cancer between the years 2006 and 2016 were included in the research retrospectively. Results: The progression-free survival (PFS) durations of patients with high expression levels of VEGF-A and with low expression levels of VEGF-A were 11 months and 10 months (p ¼ 0.44), respectively. The PFS durations of patients with high PDGF-BB expression and low PDGF-BB expression were 12 months and 10 months (p ¼ 0.16), respectively, while the PFS durations of patients with high and low c-Met expression were 8 months and 13 months (p ¼ 0.005), respectively. Metastatic overall survival was 27 months and 18 months (p ¼ 0.05) in patients with high and low VEGF-A expression levels, respectively, 31 months and 21 months (p ¼ 0.16) in patients with high and low PDGF-BB expression levels, respectively, and 21 months and 26 months (p ¼ 0.11) in patients with high and low c-Met expression levels, respectively. Conclusion: The results of this research revealed a high c-Met expression relationship with worse PFS and low VEGF-A expression associated with poor metastatic overall survival in patients with metastatic colorectal cancer receiving bevacizumab therapies.

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Predictive Significance of VEGF and HIF-1α Expression in Patients with Metastatic Colorectal Cancer Receiving Chemotherapy Combinations with Bevacizumab

Cited by 16 publications

References 31 publications

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

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

Mucinous colorectal adenocarcinoma: clinical pathology and treatment options

The prognostic importance of VEGF-A, PDGF-BB and c-MET in patients with metastatic colorectal cancer

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