Abstract

BackgroundPatients suffering from squamous cell carcinoma of the larynx (LSCC) with lymphatic metastasis have a relatively poor prognosis and often require radical therapeutic management. The mechanisms which drive metastasis to the lymph nodes are largely unknown but may be promoted by a pro-angiogenic tumor microenvironment. In this study, we examined whether the number of microvessels and the expression level of vascular endothelial growth factor (VEGF) in the primary tumor are correlated with the degree of lymph node metastasis (N-stage), tumor staging (T) and survival time in LSCC patients.MethodsTissue-Microarrays of 97 LSCC patients were analyzed using immunohistochemistry. The expression of VEGF was scored as intensity of staining (low vs high) and the number of CD31-positive vessels (median </≥7 vessels per visual field) was counted manually. Scores were correlated with N-stage, T-stage and 5-year overall survival rate.ResultsA high expression of angiogenic biomarkers was not associated with poor overall survival in the overall cohort of patients. Instead high CD31 count was associated with early stage cancer (p = 0.004) and in this subgroup high VEGF expression correlated with poor survival (p = 0.032). Additionally, in early stage cancer a high vessel count was associated with an increased recurrence rate (p = 0.004).ConclusionOnly in the early stage subgroup a high expression of angiogenic biomarkers was associated with reduced survival and an increased rate of recurrence. Thus, biomarkers of angiogenesis may be useful to identify high risk patients specifically in early stage LSCC.

Highlights

  • Patients suffering from squamous cell carcinoma of the larynx (LSCC) with lymphatic metastasis have a relatively poor prognosis and often require radical therapeutic management

  • vascular endothelial growth factor (VEGF) staining was evaluable in 87/97 patients and CD31 data in 89/97 patients

  • Angiogenic biomarkers are associated with early tumor stages In non-laryngeal HNSCC, studies by Gleich et al reported an association of angiogenesis with increasing T and N stage in oropharyngeal cancer (OPC) [30], but there was no statistical correlation between tumor aggressiveness and tumor angiogenesis in low T stages [33]

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Summary

Introduction

Patients suffering from squamous cell carcinoma of the larynx (LSCC) with lymphatic metastasis have a relatively poor prognosis and often require radical therapeutic management. The mechanisms which drive metastasis to the lymph nodes are largely unknown but may be promoted by a pro-angiogenic tumor microenvironment. Head and neck carcinomas with lymphatic metastasis usually require radical therapeutic management and are associated with poor prognosis. This is true for squamous cell carcinoma of the larynx (LSCC). Clinically of high importance, the mechanisms which drive metastasis to the lymph nodes in LSCC are still largely unknown. Some studies suggested angiogenesis as a precursor for regional lymph node metastasis [6] and implicated microvessel density in local tumor progression [7]. Other studies did not show any prognostic relation between angiogenesis and prognosis, especially in patients with LSCC [8,9,10,11]

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