Oncotarget

Research Papers:

Stromal versus tumoral inflammation differentially contribute to metastasis and poor survival in laryngeal squamous cell carcinoma

Benedikt Höing _, Oliver Kanaan, Petra Altenhoff, Robert Petri, Kruthika Thangavelu, Anke Schlüter, Stephan Lang, Agnes Bankfalvi, Sven Brandau

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Oncotarget. 2018; 9:8415-8426. https://doi.org/10.18632/oncotarget.23865

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Abstract

Benedikt Höing1, Oliver Kanaan1, Petra Altenhoff1, Robert Petri1, Kruthika Thangavelu1, Anke Schlüter1, Stephan Lang1, Agnes Bankfalvi2 and Sven Brandau1

1Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, Essen, Germany

2Institute of Pathology, University Hospital Essen, Essen, Germany

Correspondence to:

Sven Brandau, email: Sven.Brandau@uk-essen.de

Keywords: cancer-related inflammation; leukocytes; tumor stroma; head and neck cancer; nodal metastasis

Received: May 30, 2017     Accepted: November 16, 2017     Published: January 03, 2018

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.


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