Role of hypoxia-inducible factor-1α, carbonic anhydrase-IX, glucose transporter-1 and vascular endothelial growth factor associated with lymph node metastasis and recurrence in patients with locally advanced cervical cancer

Iwasaki, Keita; Yabushita, Hiromitsu; Ueno, Taiki; Wakatsuki, Akihiko

doi:10.3892/ol.2015.3524

Cited by 36 publications

(29 citation statements)

References 27 publications

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“…new blood vessels and the induces metastases in CRC (9). Thus, inhibiting HIF-1α and VEGF expression has demonstrated promise for tumor anti-angiogenesis therapy in both animal models and patients with cancer (10).…”

Section: Angiogenesis In Primary Colorectal Cancer and Matched Metastmentioning

confidence: 99%

“…The intensity of HIF-1α and VEGF staining was also determined semi-quantitatively on a scale of 0-3 as follows: 0, negative; 1, weakly positive; 2, moderately positive; and 3, strongly positive. The final staining score was determined by combining the percentage scores and staining intensities, as follows: 0 (negative), + (1-4), ++ (5-8) and +++ (9). Final staining scores of 0 or + were classified as negative expression, while final staining scores of ++ and +++ were classified as positive expression.…”

Section: Ihcmentioning

confidence: 99%

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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: Angiogenesis In Primary Colorectal Cancer and Matched Metastmentioning

confidence: 99%

Section: Ihcmentioning

confidence: 99%

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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“…In our study, 50 cases of a total of 90, showed moderate and strong positivity for HIF-1α. According to Iwasaki et al 11 , 28 cases of 54 were positive for HIF-1α, with significant association with FIGO stage (p = 0.0349) and tumor type (more significant expression in adenocarcinomas compared to squamous) but no association with lymph node metastases (p = 0.5615), LVSI (p = 0.2350), or tumor size (p = 0.5826). Our results obviously partially coincide with the already published results of other authors, but there are some disagreements.…”

Section: Discussionmentioning

confidence: 99%

HIF1α and SOX2 expression in cervical squamous cell carcinoma

Milenković

Terzić

Vranes³

et al. 2019

VOJNOSANIT PREGL

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Background/Aim. Hypoxia is one of the major changes that occurs in the tumor microenvironment. It has been observed that there are pluripotent cancer cells in the cancer cell population that affect tumor growth and their resistance to therapy. The aim of this study was to examine the expression of hypoxia-inducible factor-1 alpha (HIF-1α), endogenous marker of hypoxia, and SOX2, marker of the pluripotent stem cells existing in the normal adult tissues, in the cervical squamous cell carcinoma (SCC). Methods. The study was conducted in 90 women with invasive cervical SCC, divided into two groups-60 women in the Group A, with FIGO IB1 < 20 mm tumors (no metastases in the lymph nodes), and 30 women in the group B with tumors FIGO I-II (positive lymph nodes). The basic clinical parameters were determined by standard histopathological analysis, and the expression of HIF-1α and SOX2 by immunohistochemical examination. Results. There was a significant difference between the groups A and B, in the expression of HIF-1α (p = 0.024), but not in the expression of SOX2 (p = 0.566). Expression of HIF-1α was significantly higher in the group with lymph node metastases and invasion of lymphovascular spaces (p <0.001) but not associated with tumor size (p = 0.291) or lymphocytic stromal response (p = 0.940). The tumor grade significantly influenced the expression of HIF-1α (p = 0.013). The expression of SOX2 did not significantly correlate with any of the established clinical tumor parameters. Conclusion. A significant difference in the expression of HIF-1 α between the group with and that without metastases in lymph nodes in invasive cervical SCC could distinguish HIF-1α as a parameter of poor prognosis of the disease. The prognostic significance of SOX2 as well as a significant correlation between expression of HIF-1α and SOX2 were not established.

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“…VEGF is an important factor for tumor angiogenesis, and there have been a number of reports evaluating the VEGF expression of primary surgery specimens or that of serum in uterine cervical cancer (12)(13)(14)(15)(16). However, to the best of our knowledge, there have been no reports concerning VEGF expression in PRRCC.…”

Section: Discussionmentioning

confidence: 99%

“…VEGF-A binds to its receptor VEGFR-1, and the downstream signaling is thought to be involved in cancer proliferation and invasion (11). There have been several reports showing that the overexpression of VEGF in cancer cells or serum is correlated with radioresistance and poor disease-free survival (12)(13)(14)(15)(16), and a meta-analysis suggested that high expressions of VEGF was significantly associated with poor survival outcome (17). Although VEGF inhibitors such as bevacizumab are widely used against several…”

Section: Introductionmentioning

confidence: 99%

The upregulated expression of vascular endothelial growth factor in surgically treated patients with recurrent/radioresistant cervical cancer of the uterus

et al. 2018

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Vascular endothelial growth factor (VEGF) inhibitors have been utilized for the treatment against advanced or recurrent cervical carcinoma as a novel therapeutic modality. However, the expression level of VEGF in post-radiotherapy relapsed/persistent cervical cancer remains to be elucidated. The aim of the present study was to investigate the expression of VEGF and associated molecules using tumor samples from patients with post-radiotherapy relapsed/persistent cervical cancer. From a database of 826 patients who were treated at our institution between 2003 and 2015, eight patients with post-radiotherapy relapsed/persistent cervical cancer were identified, and 20 patients who underwent initial surgery alone were used as a control. Using samples from these patients, the expression levels of VEGF-A, VEGF receptor-1 (VEGFR-1) and hypoxia inducible factor-1α (HIF-1α) were immunohistochemically categorized as negative or weakly, moderately, or strongly positive according to the size of the staining area, and intensity. In carcinoma cells, the expression levels of VEGF-A, VEGFR-1 and HIF-1α were significantly higher in post-radiotherapy relapsed/persistent cervical cancer compared with control patients (P=0.0003, 0.0003, and 0.0001, respectively). In stroma cells, similar tendencies with statistical significance were observed (P=0.0014 and P<0.0001, respectively). In addition, the expression levels of VEGF-A and VEGFR-1 in carcinoma cells were significantly correlated with each other (P<0.0001). A significantly higher expression of VEGF was identified in post-radiotherapy relapsed/persistent cervical cancer compared with typical specimens from cervical cancer. The findings provide a novel insight into the clinical treatment for recurrent/persistent cervical cancer using a VEGF antagonist.

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Role of hypoxia-inducible factor-1α, carbonic anhydrase-IX, glucose transporter-1 and vascular endothelial growth factor associated with lymph node metastasis and recurrence in patients with locally advanced cervical cancer

Cited by 36 publications

References 27 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

HIF1α and SOX2 expression in cervical squamous cell carcinoma

The upregulated expression of vascular endothelial growth factor in surgically treated patients with recurrent/radioresistant cervical cancer of the uterus

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