Overexpression of Intrinsic Hypoxia Markers HIF1α and CA-IX Predict for Local Recurrence in Stage T1-T2 Glottic Laryngeal Carcinoma Treated With Radiotherapy

Schrijvers, Michiel L; Laan, Bernard F. A. M. van der; Bock, Geertruida H. de; Pattje, Wouter J.; Mastik, Mirjam F.; Menkema, Lorian; Langendijk, Johannes A.; Kluin, Philip M.; Schuuring, Ed; Wal, Jacqueline E. van der

doi:10.1016/j.ijrobp.2008.05.025

Cited by 91 publications

(114 citation statements)

References 28 publications

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“…Taken together, HIF-1a expression was reported to be associated with poor outcome of NSCLC patients in series that used high cut-off values and also showed a strong relationship to SCC (Swinson et al, 2004). These results are supported by other studies that showed a significant association between high HIF-1a expression and shorter survival in SCC of the head and neck (Schrijvers et al, 2008). However, these results are in disagreement with those of Volm & Koomagi (2000) who showed that NSCLC patients with HIF-1a-positive carcinomas had significantly longer median survival times than patients with HIF-1a-negative carcinomas.…”

Section: Discussionsupporting

confidence: 80%

High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer

et al. 2010

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BACKGROUND: Carbonic anhydrase IX (CAIX) is an enzyme upregulated by hypoxia during tumour development and progression. This study was conducted to assess if the expression of CAIX in tumour tissue and/or plasma can be a prognostic factor in patients with non-small cell lung cancer (NSCLC). METHODS: Tissue microarrays containing 555 NSCLC tissue samples were generated for quantification of CAIX expression. The plasma level of CAIX was determined by ELISA in 209 of these NSCLC patients and in 58 healthy individuals. The CAIX tissue immunostaining and plasma levels were correlated with clinicopathological factors and patient outcome. RESULTS: CAIX tissue overexpression correlated with shorter overall survival (OS) (P ¼ 0.05) and disease-specific survival (DSS) of patients (P ¼ 0.002). The CAIX plasma level was significantly higher in patients with NSCLC than in healthy individuals (Po0.001). A high level of CAIX in the plasma of patients was associated with shorter OS (Po0.001) and DSS (Po0.001), mostly in early stage I þ II NSCLC. Multivariate Cox analyses revealed that high CAIX tissue expression (P ¼ 0.002) was a factor of poor prognosis in patients with resectable NSCLC. In addition, a high CAIX plasma level was an independent variable predicting poor OS (Po0.001) in patients with NSCLC. CONCLUSION: High expression of CAIX in tumour tissue is a predictor of worse survival, and a high CAIX plasma level is an independent prognostic biomarker in patients with NSCLC, in particular in early-stage I þ II carcinomas.

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Section: Discussionsupporting

confidence: 80%

High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer

et al. 2010

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“…To the best of our knowledge, only one study exists in the English-language literature with regard to the correlation between HIF-1α and GLUT-1 expression in laryngeal carcinoma and their association with clinicopathological features (21). This study identified no correlation between GLUT-1 overexpression and clinical outcome parameters of laryngeal carcinoma.…”

Section: Introductionmentioning

confidence: 60%

“…only one study in the English-language literature with regard to the correlation between HIF-1α and GLUT-1 expression in laryngeal carcinoma (21). In a previous study, 67.5% (27/40) of patients with laryngeal carcinoma were immunopositive for HIF-1α and HIF-1α expression was associated with T stage and lymph node metastasis (22).…”

mentioning

confidence: 97%

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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“…HIF-1α has been regarded as a key element to mediate the function of HIF-1 to activate a set of hypoxia-inducible genes, regulating tumor angiogenesis (Park et al, 2010), metastasis (Jing et al, 2012), resistance to therapy (Zhu et al, 2005;Huang et al, 2010) and other adaptations to hypoxia. Recently, several literatures have reported that overexpression of HIF-1α protein is significantly correlated with local recurrence, tumor progression and metastasis in human laryngeal carcinoma (Schrijvers et al, 2008;Wu et al, 2010), suggesting that HIF-1α might serve as a determinant of malignant biological behaviors of laryngeal cancer cells. However, it is far from clear whether HIF-1α is responsible for the occurrence of MDR in laryngeal cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Induced Multidrug Resistance of Laryngeal Cancer Cells via Hypoxia-inducible Factor-1α

Li¹,

Dong²,

Wang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Overexpression of Intrinsic Hypoxia Markers HIF1α and CA-IX Predict for Local Recurrence in Stage T1-T2 Glottic Laryngeal Carcinoma Treated With Radiotherapy

Cited by 91 publications

References 28 publications

High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer

High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer

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

Hypoxia Induced Multidrug Resistance of Laryngeal Cancer Cells via Hypoxia-inducible Factor-1α

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