Lymphatic Vessel Density, Nodal Metastases, and Prognosis in Patients With Head and Neck Cancer

Audet, Nathalie; Beasley, Nigel; MacMillan, Christina; Jackson, David G.; Gullane, Patrick; Kamel‐Reid, Suzanne

doi:10.1001/archotol.131.12.1065

Cited by 64 publications

(55 citation statements)

References 20 publications

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“…In a multivariate analysis, the Chalkley score was found to be significantly associated with the presence of nodal metastases at presentation. A similar association has also been shown in head and neck cancer (Audet et al, 2005).…”

Section: Chalkley Countingsupporting

confidence: 82%

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

et al. 2006

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The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra-and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment. Metastasis is the leading cause of cancer mortality. Metastatic cancer cells can escape from their site of origin and spread to distant organs through invasion of the vascular system and/or the lymphatic system. Tumour vascularisation is widely accepted as a bona fide indicator of tumour growth, metastases and patient survival. In 1996, Peter Vermeulen et al (1996) published a first international consensus on the methodology and criteria of the evaluation of angiogenesis quantification in solid tumours and 5 years later, a second consensus report, in which new concepts and mechanisms of tumour vascularisation were integrated, appeared (Vermeulen et al, 2002). Both reports were aimed at improving the standardisation of angiogenesis quantification in order to allow intratumourous microvessel density to be applied as a prognostic indicator and, moreover, as a reliable predictor of the risk of malignant transformation of premalignant lesions and of response to cancer treatment. Contrary to angiogenesis, the de novo formation of lymphatic vessels or lymphangiogenesis and its role in promoting the metastatic spread of tumour cells has only recently become a focal point of cancer research with an increasing number of studies showing a relationship between patient survival and lymphatic density in different tumour types. In order to confirm the potential prognostic value of lymphangiogenesis in patients with cancer, a quantification method that is characterised by a low intra-and interobserver variability needs to be developed. In this first consensus report, we would like to provide an overview of current concepts of the lymphatic vasculature and its regulating factors and propose guidelines for the estimation of the ongoing lymphangiogenesis in solid human tumour sections.

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Section: Chalkley Countingsupporting

confidence: 82%

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

et al. 2006

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“…In HNSCC, LVD measurements have been suggested as potential indicators of the risk of lymph node metastasis [6][7][8][9]. We believe that these discrepancies between SCC and salivary carcinomas regarding LVD and risk for nodal metastasis may reflect genuine differences between the malignant behaviors of these two types of carcinomas of the head and neck region.…”

Section: Discussionmentioning

confidence: 99%

“…However, a high lymph vessel density (LVD) seems to be an indicator of the risk of lymph node metastasis in HNSCC [6][7][8][9]. Regarding salivary gland tumors, the lymphatic vessels have rarely been studied [10][11][12] and in a particular type of salivary carcinoma, i.e.…”

mentioning

confidence: 99%

Lymphatic vessel density and expressions of lymphangiogenic growth factors in salivary carcinomas

Mf¹,

Af²,

Ll³

et al. 2011

neo

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Nodal metastasis is an important prognostic indicator in head and neck cancers, including salivary carcinomas. In these, the risk for lymph node metastasis is variable and strongly associated with the tumor histologic type. The aim of the current study was to evaluate the lymphatic vessel density (LVD) and expressions of lymphangiogenic growth factors by tumor cells in different histologic types of salivary carcinomas subdivided according to the risk for nodal metastasis. In 15 high-risk (undifferentiated, high-grade mucoepidermoid and salivary duct carcinomas) and 60 low/moderate-risk tumors (adenoid cystic, low/intermediate-grade mucoepidermoid, acinic cell, myoepithelial, epithelial-myoepithelial and polymorphic lowgrade carcinomas) the expressions of vascular endothelial growth factor-C (VEGF-C), hepatocyte growth factor (HGF) and D2-40 (for assessing LVD) were examined. No significant differences were encountered between high-and low/moderate/-risk carcinomas regarding LVD and VEGF-C or HGF expressions. Furthermore, the expression of these proteins did not correlate with LVD. Lymphatic vascular invasion was found mainly in high-risk carcinomas. Intratumoral LVD was significantly lower than peritumoral, regardless of the risk for metastasis and primary site of the lesion. The histologic types of salivary carcinomas which are associated with high-risk for nodal metastasis do not present increased LVD or VEGF-C and HGF expressions. The greater tendency for metastasis in these carcinomas seems to be related to their capacity to invade lymph vessels. Further studies on tumor cell interactions with lymphatic endothelial cells are needed to improve our understanding of the metastatic potential of salivary carcinomas. Key words: lymph vessels, salivary carcinoma, VEGF-C, HGF.Nodal metastasis is an important prognostic predictor in head and neck cancers, including salivary carcinomas. The risk for lymph node metastasis in these carcinomas is highly variable (9% -85%) [1] and strongly associated with the tumor histologic type [1][2][3][4][5]. It is a general consensus that high-grade mucoepidermoid carcinomas, salivary duct carcinomas, undifferentiated carcinomas and squamous cell carcinomas are high-risk tumors for nodal metastasis [1,[3][4][5]. In these the risk for neck metastasis has been described to be >50% [1] and, thus, elective neck dissection is considered in their management [1][2][3].Lymph vessels provide the main avenue for nodal metastasis and in head and neck squamous cell carcinoma (HNSCC) it has been shown that tumors of different anatomic regions do not vary significantly in their lymphangiogenic properties [6,7]. However, a high lymph vessel density (LVD) seems to be an indicator of the risk of lymph node metastasis in HNSCC [6][7][8][9]. Regarding salivary gland tumors, the lymphatic vessels have rarely been studied [10][11][12] and in a particular type of salivary carcinoma, i.e. in those arising in pleomorphic adenomas (CXPA) the lymphatic network was found to be composed mainly of pre-existing ...

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“…Important controversial data have been reported showing that peritumoral LVD is more importantly associated with the presence of metastases than intratumoral LVD (18) . Conversely, there are data demonstrating that intratumoral vessels are critical for lymphatic metastasis (3) . Interestingly, it was reported that, in melanomas, the size of peritumoral lymphatic vessels is the most significant independent factor that correlates with metastasis (5) .…”

Section: Discussionmentioning

confidence: 99%

Lymphangiogenesis: from the pig embryos to cancer

Longatto‐Filho¹,

Duarte²,

Schmitt³

2008

J. Bras. Patol. Med. Lab.

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The discovery and the comprehension of lymphatic vessels suffered several historical delays and setbacks. The inherent anatomical problems slowed down the precise identification of the lymphatic system during the development of medical science. Gasparo Aselli, an Italian surgeon and anatomist, was the first to describe the lymphatic vessels in 1627 (De Lacteibus sive Lacteis Venis). However, most original descriptions that report the morphology of the lymphatic system in different organisms were done during the 19th and the 20th centuries. The recent identification of specific lymphatic vasculature molecular markers allows a more accurate identification and characterization of the lymphatic system evolution in different organs, as well as its role in different pathological conditions, including cancer. This study summarizes the current understanding of lymphangiogenesis in tumour progression, as well as it presents a review of the promising data regarding the prognostic value of lymphatic density and the use of therapeutic lymphangiogenic molecules. resumo abstract A descoberta dos vasos linfáticos e sua compreensão enfrentaram uma série de atrasos e dificuldades históricos. As inerentes dificuldades anatômicas retardaram a identificação precisa da rede vascular linfática durante o desenvolvimento da ciência médica. Gasparo Aselli, um anatomista e cirurgião italiano, foi o primeiro a descrever os vasos linfáticos, em 1627 (De Lacteibus sive Lacteis Venis). Entretanto, a maioria das descrições originais que relatam a morfologia do sistema linfático nos diferentes organismos foi realizada depois, entre os séculos XIX e XX. A recente identificação de marcadores moleculares específicos à vasculatura linfática permite agora identificação e caracterização mais acuradas da evolução da rede linfática nos vários órgãos e em diferentes situações, inclusive no câncer. Esta revisão resume o conhecimento sobre a linfangiogênese na progressão tumoral, bem como apresenta uma síntese dos dados mais promissores em relação ao valor prognóstico da densidade linfática e da utilização das moléculas linfangiogênicas como alvo terapêutico.

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Lymphatic Vessel Density, Nodal Metastases, and Prognosis in Patients With Head and Neck Cancer

Cited by 64 publications

References 20 publications

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

Lymphatic vessel density and expressions of lymphangiogenic growth factors in salivary carcinomas

Lymphangiogenesis: from the pig embryos to cancer

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