Tumor microenvironment in head and neck squamous cell carcinomas: Predictive value and clinical relevance of hypoxic markers. A review

Hoogsteen, Ilse J.; Marres, H.A.M.; Bussink, Johan; Kogel, Albert J. van der; Kaanders, Johannes H.A.M.

doi:10.1002/hed.20543

Cited by 95 publications

(76 citation statements)

References 106 publications

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“…High expression of HIF-1a and VEGF is associated with higher tumor aggressiveness and an unfavorable prognosis in many types of solid cancers (Manders et al 2003, Hoogsteen et al 2007. Hypoxia initially induces increased expression of HIF-1a, but during sustained hypoxia, the amount of HIF-1a mRNA is reduced (Wenger et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of the natural antisense hypoxia-inducible factor-1 transcript is associated with malignant pheochromocytoma/paraganglioma

Span

Rao²,

Ophuis³

et al. 2011

Endocrine Related Cancer

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Paragangliomas (PGLs) have widely different metastastic potentials. Two different types of PGLs can be defined by expression profiling. Cluster 1 PGLs exhibit VHL and/or succinate dehydrogenase (SDH) mutations and a pseudohypoxic phenotype. RET and neurofibromatosis type 1 (NF1) mutations occur in cluster 2 tumors characterized by deregulation of the RAS/RAF/MAP kinase signaling cascade. Sporadic PGLs can exhibit either profile. During sustained hypoxia, a natural antisense transcript of hypoxia-inducible factor 1 (aHIF) is expressed. The role of aHIF in the metastatic potential of PGL has not yet been investigated. The aim was to test the hypothesis that genotype-specific overexpression of aHIF is associated with an increased metastatic potential. Tumor samples were collected from 87 patients with PGL. Quantitative PCR was performed for aHIF, vascular endothelial growth factor (VEGF), aquaporin 3, cytochrome b561, p57Kip2, slit homolog 3, and SDHC. Expression was related to mutation status, benign versus malignant tumors, and metastasis-free survival. We found that both aHIF and VEGF were overexpressed in cluster 1 PGLs and in metastatic tumors. In contrast, slit homolog 3, p57Kip2, cytochrome b561, and SDHC showed overexpression in non-metastatic tumors, whereas no such difference was observed for aquaporin 3. Patients with higher expression levels of aHIF and VEGF had a significantly decreased metastasisfree survival. Higher expression levels of SDHC are correlated with an increased metastasis-free survival. In conclusion, we not only demonstrate a higher expression of VEGF in cluster 1 PGL, fitting a profile of pseudohypoxia and angiogenesis, but also of aHIF. Moreover, overexpression of aHIF and VEGF marks a higher metastatic potential in PGL.

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Section: Introductionmentioning

confidence: 99%

Overexpression of the natural antisense hypoxia-inducible factor-1 transcript is associated with malignant pheochromocytoma/paraganglioma

Span

Rao²,

Ophuis³

et al. 2011

Endocrine Related Cancer

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“…There is an association between OPN expression, hypoxia and anemia. However, an explanation stating that low Hb levels are directly responsible for low oxygen pressures would be simple and inconclusive (Hoogsteen et al, 2007). Cause and effect relationships in this process require further studies.…”

Section: Discussionmentioning

confidence: 99%

“…Tumor hypoxia is seen most frequently in cervical cancer and squamous cell head and neck cancer (SCHNC) (Vaupel et al, 1998;Nordsmak et al, 2005;Hoogsteen et al, 2007). Tumor hypoxia can be evaluated by several methods.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Osteopontin in Patients Treated with Primary Radiotherapy for Head and Neck Cancer

Etiz¹,

Ataizi²,

Bayman³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: The prognostic value of tumor osteopontin (OPN) in patients with squamous-cell head and neck cancer (SCHNC) was investigated. Materials and Methods: OPN expression was assessed by immunohistochemical methods in 50 patients, who were treated with primary radiotherapy (RT) for locally advanced SCHNC. The effects of OPN on clinical parameters, local-regional control after RT and metastasis-free survival, was assessed. Results: The rate of OPN expression in tumor tissue was 76%. OPN positive cases had lower Hb levels (p=0.088). Mean time to local recurrence was 53.8 months (SE 3.9) in OPN-negative cases and 39.1 months (SE 4.7) in OPN-positive cases (p=0.047). OPN increased the risk of local recurrence 5.9 times (p=0.085). It had no effect on metastasis-free (p=0.116) or overall survival (p=0.123). OPN was positive in 12 of 19 cases that developed grade 3-4 acute radiation dermatitis (p=0.096). Conclusions: OPN expression is associated with an increase in local recurrence in patients who were treated with primary RT for locally advanced SCHNC.

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“…Further work should be done to explore whether NPC patients benefit from anti-angiogenic therapies and to measure the extent to which laboratory evaluation of vessel density or upstream mediators predicts response to treatment [33,34]. …”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus Latent Membrane Protein 1 is not Associated with Vessel Density nor with Hypoxia Inducible Factor 1 Alpha Expression in Nasopharyngeal Carcinoma Tissue

Benders

Tang²,

Middeldorp

et al. 2009

Head and Neck Pathol

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Hypoxia-inducible factor-1a (HIF-1a) and the neo-angiogenic factors induced as a result of hypoxiainducible factor transcriptional activation may contribute to tumorigenesis by inducing vessel formation that in turn provides oxygen and nutrients promoting tumor expansion. In vitro studies of nasopharyngeal carcinoma (NPC), an aggressive malignancy that is nearly always infected by Epstein-Barr virus, show HIF-1a is upregulated by viral latent membrane protein 1 (LMP1). The current study used immunohistochemistry to examine the extent to which HIF-1a and LMP1 are co-expressed in naturally infected NPC tissues. Analytic procedures were optimized for sensitive localization of HIF-1a and LMP1 in fixed tissue sections using immunohistochemistry with sensitive fluorescent and signal amplification technologies. Vessel density was quantified by CD31 immunohistochemistry. LMP1 was expressed focally in all 18 NPCs examined, including 7/8 in situ lesions. There was no consistent co-localization with HIF-1a which was usually only weakly expressed in a subset of neoplastic cells. Neither LMP1 nor HIF-1a expression correlated with vessel density, and degree of vascularization varied widely among cases. Advanced immunohistochemical technologies reveal that LMP1 is expressed more commonly than previously reported in NPC. There is no consistent relationship between LMP1 and either HIF-1a expression or degree of microvasculature. The biologic basis for the wide variation in vessel density deserves further investigation.

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Tumor microenvironment in head and neck squamous cell carcinomas: Predictive value and clinical relevance of hypoxic markers. A review

Abstract: A number of markers and marker profiles have emerged that may have potential as a predictive assay. Validation of these candidate assays requires testing in prospective trials comparing standard treatment against experimental treatments targeting the related microregional constituent.

Cited by 95 publications

References 106 publications

Overexpression of the natural antisense hypoxia-inducible factor-1 transcript is associated with malignant pheochromocytoma/paraganglioma

Overexpression of the natural antisense hypoxia-inducible factor-1 transcript is associated with malignant pheochromocytoma/paraganglioma

Prognostic Value of Osteopontin in Patients Treated with Primary Radiotherapy for Head and Neck Cancer

Epstein-Barr Virus Latent Membrane Protein 1 is not Associated with Vessel Density nor with Hypoxia Inducible Factor 1 Alpha Expression in Nasopharyngeal Carcinoma Tissue

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