Abstract

In solid tumors the biology and clinical course are strongly influenced by the interaction of tumor cells and infiltrating stromal host cells. The aim of this study was to assess the relative importance of stromal vs. tumoral inflammation for metastasis and survival in patients with laryngeal squamous cell carcinoma (LSCC).In 110 patients with tissues from histologically proven LSCC the expression of CD45, CD11b, CD3, MMP-9 and COX-2 was semiquantitatively analyzed in stromal regions and tumor nests.CD45, CD11b, CD3 and MMP-9 positive cells were more abundant in stroma whereas COX-2 was predominantly expressed in epithelial tumor nests. High expression of stromal CD45 and CD11b on immune cells in tumor regions correlated with COX-2 expression on tumor cells. High levels of CD45 in stroma as well as CD11b and COX-2 in tumor nests were associated with increased metastasis. In contrast, high frequencies of CD3 cells in the tumor core area were associated with reduced metastasis. Overall survival was reduced in patients with high stromal CD45, high tumoral CD11b and high tumoral COX-2 expression.This is the first study which separately analyzes peritumoral stroma and tumor core area in laryngeal squamous cell carcinoma in terms of CD45, CD11b, CD3, MMP-9 and COX-2 expression. Our results indicate that stroma and tumor islands need to be considered as two separate compartments in the inflammatory tumor microenvironment. Inflammatory stromal leukocytes, abundant myeloid cells in tumor regions and high expression of COX-2 on tumor cells are linked to metastatic disease and poor overall survival.

Highlights

  • Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide with well-defined risk factors such as alcohol or tobacco abuse

  • CD45, CD11b, CD3, matrix metalloproteases (MMP)-9 and COX-2 are differentially expressed between stroma and tumor

  • The aim was to test whether these markers of cancer-related inflammation are associated with survival and metastatic state and whether a potential association differs between inflammation localized in stromal regions versus tumor islands

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Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide with well-defined risk factors such as alcohol or tobacco abuse. Necrotic cell death and upregulated protumoral cellular pathways promote the production of proinflammatory mediators and growth factors; this includes matrix metalloproteases (MMP), VEGF or cyclooxygenase, which are produced by different types of immune and tumor cells [3, 4]. This enables the tumor to invade and proliferate by degrading extracellular matrix or by forming new blood vessels [5]. In this study, we employed five simple and well established biomarkers and determined the correlation of stromal versus tumoral inflammation with metastatic disease in laryngeal squamous cell carcinoma (LSCC)

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