Angiogenesis as a Prognostic Marker in Early Head and Neck Cancer

Dray, Todd G.; Hardin, Nicholas J.; Sofferman, Robert A.

doi:10.1177/000348949510400911

Cited by 79 publications

(61 citation statements)

References 12 publications

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“…In this study, tumor vascularity was not predictive of the response of a tumor to chemoradiotherapy [40]. Tumor angiogenesis has shown to positively correlate with nodal metastasis in carcinoma of the tongue floor of mouth and nasopharynx [41][42][43][44][45][46]. However, tumor microvessel density has been reported to not serve as a predictor of lymph node metastasis by several authors examining tumors from various sites in the head and neck.…”

Section: Angiogenesismentioning

confidence: 55%

The Biology of Distant Metastases in Head and Neck Cancer

Petruzzelli

2001

ORL

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The detection and treatment of metastatic cancer continues to be a challenge for the head and neck oncologist. Unfortunately, head and neck cancer patients who develop distant metastases commonly present late in their course and rapidly succumb to their disease, despite advances in imaging technologies and increased sophistication of biochemical analyses. The development of a rational approach to detection and treatment of metastatic head and neck cancers should begin with an understanding of how these tumors occur and which patients are at greatest risk for developing them. This article presents an overview of the biological processes resulting in the speed of a malignancy from one site to another, with particular attention to head and neck carcinomas. The basic histopathologic, immunology and biochemical abnormalities associated with the development of these secondary tumors are also discussed.

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Section: Angiogenesismentioning

confidence: 55%

The Biology of Distant Metastases in Head and Neck Cancer

Petruzzelli

2001

ORL

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“…For squamous cells carcinomas of the head and neck, as for other tumour types such as carcinoma of the breast, conflicting results have been reported. Some investigators found a correlation between vascular density and metastatic potential (Gasparini et al, 1993;Albo et al, 1994;Shpitzer et al, 1996;Murray et al, 1997), whereas others did not (Leedy et al, 1994;Dray et al, 1995;Zätterström et al, 1995;Janot et al, 1996;Moriyama et al, 1997;Salven et al, 1997;Burian et al, 1999). In this study no correlation was found between vascular density and N-stage, even when the 75th percentile value or the highest value of the subareas were used.…”

Section: Vascular Parametersmentioning

confidence: 99%

“…Single parameters such as polarographic pO 2 measurements and microvascular density have been demonstrated to be prognostic indicators in a variety of tumour types, including carcinomas of the head and neck (Gatenby et al, 1987;Dray et al, 1995;Zätterström et al, 1995;Jenssen et al, 1996;Nordsmark et al, 1996;Brizel et al, 1997). However, considering the complexity of the micro-environmental system, it is unlikely that a single parameter can reliably predict treatment outcome on an individual basis.…”

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confidence: 99%

Vascular architecture and hypoxic profiles in human head and neck squamous cell carcinomas

et al. 2000

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The relevance of blood flow for the outcome of radiation treatments was already described by Schwartz in 1909. He noticed that skin reactions were less severe when the radium applicator was firmly pressed to the skin. It was Cramer in 1935 who gave the first suggestion of an 'oxygen effect'. He found that mouse mammary tumours with a well developed stroma and vascular network were more radiosensitive than tumours with a more delicate stromal component. He suggested that the radiosensitive tumours had a better blood supply and, consequently, were better oxygenated. Later, Gray et al (1953) established the importance of tumour oxygenation for radiotherapy.The tumour micro-environment is a key factor in tumour biology and has great impact on clinical radiotherapy as well as other cancer treatments. Single parameters such as polarographic pO 2 measurements and microvascular density have been demonstrated to be prognostic indicators in a variety of tumour types, including carcinomas of the head and neck (Gatenby et al, 1987;Dray et al, 1995;Zätterström et al, 1995;Jenssen et al, 1996;Nordsmark et al, 1996;Brizel et al, 1997). However, considering the complexity of the micro-environmental system, it is unlikely that a single parameter can reliably predict treatment outcome on an individual basis. Multiple parameter analysis will be necessary to acquire a better understanding of the tumour micro-environment and to obtain a 'predictive profile' which can guide the clinician in the selection of patients for new treatment strategies.A computerized image analysis system for multi-parameter analysis has been developed in our institute (Rijken et al, 1995). The method involves computer controlled microscopic scanning of immunohistochemically stained tissue sections. It allows quantitative and simultaneous analysis of vascular parameters, oxygenation status and proliferation parameters. We have recently published our experience with this method in xenografted human tumours (Bussink et al, 1998(Bussink et al, , 1999.We now apply this method also to tumour biopsies from patients with squamous cell carcinomas of the head and neck. Before a biopsy was taken, the patients were injected with Hypoxyprobe-1 (pimonidazole hydrochloride) as a hypoxia marker. Pimonidazole can easily be dissolved in saline, has a low toxicity, and an efficient tumour uptake. So far pimonidazole has proven to be an effective hypoxia marker for human tumours of the cervix and head and neck (Kennedy et al, 1997;Raleigh et al, 1998;. In the present study we report the results of the analysis of biopsy material from 21 patients with squamous cell carcinoma of the head and neck. MATERIALS AND METHODS PatientsPatients with primary laryngeal, oropharyngeal (stage III-IV) or hypopharyngeal (stage II-IV) squamous cell carcinomas were Summary Tumour oxygenation and vasculature are determinants for radiation treatment outcome and prognosis in patients with squamous cell carcinomas of the head and neck. In this study we visualized and quantified these factors which m...

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“…3,4 In head and neck squamous cell carcinoma, the quantification of tumor angiogenesis by intratumoral microvessel counting correlates with poor clinical outcome, 5,6 but results of various studies are conflicting and inconclusive in regard of the size of the estimated risk. 7,8 A number of putative angiogenic factors such as basic fibroblast growth factor, platelet-derived growth factor, interleukins, and vascular endothelial growth factor (VEGF), are expressed in head and neck squamous cell carcinoma. 4 VEGF is considered a leading candidate for tumor angiogenesis in head and neck squamous cell carcinoma, exhibiting its effect in the vasculature in a paracrine pattern.…”

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Potential autocrine function of vascular endothelial growth factor in head and neck cancer via vascular endothelial growth factor receptor-2

et al. 2005

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Vascular endothelial growth factor is a peptide with well-defined actions on the vasculature and fundamental role in tumor angiogenesis. Its action in vascular endothelium is exerted in a paracrine manner. The immunohistochemical expression of this protein by cancer cells in head and neck squamous cell carcinoma was correlated with increased tumor aggressiveness and poor survival in previous studies. In the past years, an increasing amount of studies demonstrated potential autocrine action of vascular endothelial growth factor in various neoplasms. However, the existence and the impact of such autocrine action in head and neck cancer have not been demonstrated yet. In this retrospective study, we evaluated the expression of vascular endothelial growth factor and its receptors in neoplastic cells, in a cohort of patients with head and neck squamous cell carcinoma, and compared this expression with tumor aggressiveness, clinicopathologic parameters and outcome. High expression of vascular endothelial growth factor was strongly correlated with high expression of vascular endothelial growth factor receptor-2 (but not vascular endothelial growth factor receptor-1) on the cancer cells (Po0.001). The co-overexpression of both the protein and vascular endothelial growth factor receptor-2 was associated with higher tumor proliferation rate (Po0.001). The above cooverexpression also correlated with worse survival (log rank Po0.05) in patients with oral-larynx squamous cell carcinoma. Our results suggest that an autocrine vascular endothelial growth factor loop, mediated via vascular endothelial growth factor receptor-2, probably exists in head and neck squamous cell carcinoma. These observations support the hypothesis that the use of vascular endothelial growth factor receptor-2 inhibitors as adjuvant antiangiogenic therapy might have beneficial effects for these patients, by disrupting both paracrine (endothelial-dependent) and autocrine actions of vascular endothelial growth factor.

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Angiogenesis as a Prognostic Marker in Early Head and Neck Cancer

Cited by 79 publications

References 12 publications

The Biology of Distant Metastases in Head and Neck Cancer

The Biology of Distant Metastases in Head and Neck Cancer

Vascular architecture and hypoxic profiles in human head and neck squamous cell carcinomas

Potential autocrine function of vascular endothelial growth factor in head and neck cancer via vascular endothelial growth factor receptor-2

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