The relation between hypoxia‐inducible factor (HIF)‐1alpha expression with p53 expression and outcome in surgically treated supraglottic laryngeal cancer

Cabanillas, Rubén; Rodrigo, Juan P.; Secades, Pablo; Astudillo, Aurora; Nieto, Carlos Suárez; Chiara, María‐Dolores

doi:10.1002/jso.21243

Cited by 20 publications

(21 citation statements)

References 32 publications

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“…HIF-1α and GLUT-1 are the intrinsic hypoxia markers that have been studied the most in various tumours (13)(14)(15)(16)(17)(18). Nevertheless, few studies have investigated the value of HIF-1α (22,23,28,29) or GLUT-1 expression (24,25) alone for the prediction of clinical outcome and survival rate of laryngeal carcinoma and, to the best of our knowledge, there is …”

Section: Discussionmentioning

confidence: 99%

“…Wildeman et al suggested that the effect of hypoxia-related proteins, including carbonic anhydrase IX and HIF-1α, on an increased risk for local recurrence of laryngeal carcinoma is stronger following radiotherapy (29). Cabanillas et al reported a significant positive correlation between HIF-1α and T classification, but no association was observed with other clinicopathological variables or with the prognosis of supraglottic laryngeal squamous cell carcinoma (28). Although HIF-1α expression was significantly associated with a poorer survival rate in a univariate model in the present study, multivariate analysis revealed no significant association.…”

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confidence: 99%

“…Although HIF-1α expression was significantly associated with a poorer survival rate in a univariate model in the present study, multivariate analysis revealed no significant association. These apparent discrepancies concerning the correlation between HIF-1α and survival rate may be attributable to variations in therapeutics or in patient populations, as the disease course and prognosis of head and neck squamous cell carcinoma are known to differ regionally and different patients may carry distinct genetic alterations (28). These limitations may make studies of HIF-1α in head and neck squamous cell carcinoma susceptible to bias (28).…”

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Expression and significance of hypoxia-inducible factor-1α and glucose transporter-1 in laryngeal carcinoma

Chen

Jianying

et al. 2012

Oncology Letters

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Abstract. Malignant cells show increased glucose uptake in vitro and in vivo. This process is considered to be mediated by glucose transporters (GLUTs). Hypoxia-inducible factor-1α (HIF-1α) may upregulate GLUT-1 expression. Little is known about the correlation between HIF-1α and GLUT-1 expression in laryngeal carcinoma. The current study investigated this correlation immunohistochemically, according to various clinical and pathological features, in 49 paraffin-embedded archival tissue blocks from patients with laryngeal squamous cell carcinoma. HIF-1α and GLUT-1 expression was detected in 63.3 (31/49) and 55.1% (27/49) of the tumour samples, respectively. HIF-1α expression was significantly correlated with lymph node classification (P= 0.018), recurrence (P= 0.02) and metastasis (P= 0.031). GLUT-1A expression was significantly associated with recurrence (P=0.02) and metastasis (P=0.01). Univariate analyses revealed that HIF-1α (χ 2 =8.2; P=0.004) and GLUT-1 expression (χ 2 =9.0; P=0.003) were significantly associated with a poorer survival rate. In a multivariate analysis, GLUT-1 expression (P=0.006) was a significant predictor of poor survival rate, as well as the primary tumour site, lymph node invasion and distant metastasis. Based on Spearman's analysis, GLUT-1 expression and phosphatidylinositol 3-kinase (PI3K) expression were significantly correlated (r=0.504; P=0.000). This is the first study to demonstrate a significant correlation between GLUT-1 and HIF-1α expression in laryngeal carcinoma and to show increased GLUT-1 expression as an independent survival rate predictor. These results suggest that GLUT-1 is a potential new therapeutic target for laryngeal carcinoma.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Expression and significance of hypoxia-inducible factor-1α and glucose transporter-1 in laryngeal carcinoma

Chen

Jianying

et al. 2012

Oncology Letters

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“…Following a review of the literature, only 13 studies on the topic of laryngeal carcinoma and HIF were identified (Table I). These studies all examined the expression of HIF-1α only, and none investigated HIF-1α mRNA expression levels from in vivo samples (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). The current study is the first to present full quantitative data regarding the mRNA expression levels of HIF-1α and HIF-2α in laryngeal carcinoma samples, and is the first to report on the mRNA expression levels of HIF-3α in an in vivo study of a malignant neoplasm.…”

Section: Discussionmentioning

confidence: 99%

Relative quantitative expression of hypoxia-inducible factor-1α, −2α and −3α, and vascular endothelial growth factor A in laryngeal carcinoma

et al. 2015

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Abstract. The aim of the present study was to determine the relative quantitative expression of hypoxia-inducible factor (HIF)-1α, -2α and -3α, and VEGF-A in laryngeal carcinoma. A total of 63 patients with carcinoma of the larynx were enrolled in the study. Total RNA was isolated from fresh, frozen normal and tumor tissues of each patient, and quantitative polymerase chain reaction was performed. HIF-1α was upregulated in the majority of patients (44 patients; 69.84%). By contrast, only 7 (11.11%) patients from the whole group displayed HIF-2α overexpression, while the HIF-3α isoform was silenced in the majority of patients (48 patients, 76.19%). A small group of 5 (7.94%) patients exhibited significant overexpression of the HIF-3α isoform. VEGF-A expression was significantly higher (P<0.05) in patients with upregulated HIF-1α (2.72±1.41 RQ) compared with patients without upregulated HIF-1α (1.86±1.46 RQ). There was a moderate positive correlation between mRNA expression levels of HIF-1α and VEGF-A (r s = 0.392; P<0.005). To the best of our knowledge, this study is first to report quantitative data with regard to the expression of all three HIF isoforms in malignant neoplasms. The findings suggest the existence of specific phenotypes of HIF expression in laryngeal carcinoma, where the HIF switch is absent.

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“…Several studies have focused on whether HIF-1α expression in human laryngeal carcinoma tissue is associated with tumor progression and lymph node metastasis. However, those conclusions have been inconsistent thus far (11,12). …”

Section: Introductionmentioning

confidence: 95%

Expression and significance of hypoxia-inducible factor-1α and MDR1/P-glycoprotein in laryngeal carcinoma tissue and hypoxic Hep-2 cells

Xie

Chen

et al. 2013

Oncology Letters

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The present study aimed to evaluate the expression of hypoxia-inducible factor-1α (HIF-1α) and MDR1/P-glycoprotein (P-gp) in human laryngeal squamous cell carcinoma (LSCC) tissues, and also to investigate the regulation of MDR1 gene expression by HIF-1α in Hep-2 cells under hypoxic conditions. The expression of HIF-1α and MDR1/P-gp in human LSCC tissues was examined using immunohistochemistry. The HIF-1α and MDR1 gene expression in the Hep-2 cells was detected using real-time quantitative reverse transcription (QRT)-PCR and western blot analysis under normoxic and hypoxic conditions. In hypoxia, HIF-1α expression was inhibited by RNA interference. HIF-1α and MDR1/P-gp expression was high in the LSCC tissues and was associated with the clinical stage and lymph node metastasis (P<0.05). HIF-1α expression was positively correlated with MDR1/P-gp expression (P<0.01). In the Hep-2 cells, HIF-1α and MDR1/P-gp expression significantly increased in response to hypoxia. The inhibition of HIF-1α expression synergistically downregulated the expression of the MDR1 gene in hypoxic Hep-2 cells. HIF-1α expression is positively correlated with MDR1/P-gp expression in LSCC, and the two proteins may be able to serve as potential biomarkers for predicting the malignant progression and metastasis of LSCC. HIF-1α may be critical for the upregulation of MDR1 gene expression induced by hypoxia in Hep-2 cells.

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The relation between hypoxia‐inducible factor (HIF)‐1alpha expression with p53 expression and outcome in surgically treated supraglottic laryngeal cancer

Abstract: The data suggest that HIF-1alpha expression does not have a prognostic value in surgically treated supraglottic laryngeal SCC, and that immunohistochemical determination of p53 does not allow improving the clinical significance of HIF-1alpha.

Cited by 20 publications

References 32 publications

Expression and significance of hypoxia-inducible factor-1α and glucose transporter-1 in laryngeal carcinoma

Expression and significance of hypoxia-inducible factor-1α and glucose transporter-1 in laryngeal carcinoma

Relative quantitative expression of hypoxia-inducible factor-1α, −2α and −3α, and vascular endothelial growth factor A in laryngeal carcinoma

Expression and significance of hypoxia-inducible factor-1α and MDR1/P-glycoprotein in laryngeal carcinoma tissue and hypoxic Hep-2 cells

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