A case of squamous cell carcinoma of the head and neck producing granulocyte-colony stimulating factor with marked leukocytosis

Abstract

In squamous cell carcinoma of the head and neck (SCCHN), tumor cells have been shown to secrete detectable amounts of various cytokines, such as interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-β. These tumor-derived factors might be responsible for promoting malignancy. Here, we describe a SCCHN patient with tumor produced G-CSF and characterized by marked leukocytosis. In this 45-year-old man, severe leukocytosis developed in parallel with aggressive tumor growth. G-CSF production by the tumor was confirmed by immunohistochemistry (IHC). Serum G-CSF levels were elevated. The leukocyte counts and the blood G-CSF level decreased following a course of radiotherapy. Tumor cells were also positive for G-CSF receptor, suggesting autocrine growth regulation by G-CSF. Moreover, the tumor cells were also investigated by IHC with anti-p53, anti-P-glycoprotein (P-gp), anti-thymidylate synthase (TS), and anti-dihydropyrimidine dehydrogenase (DPD), which molecules are thought to contribute the acquisition of therapeutic resistance. The tumor cells were positively stained for TS and DPD, but neither p53 nor P-gp. These results suggest that a variety of molecules may be responsible for acquisition of high malignancy.

Introduction

Granulocyte-colony stimulating factor (G-CSF) is a cytokine mainly produced by activated T cells, macrophages, and endothelial cells. It is usually generated at sites of infection, acting as an endocrine hormone to mobilize neutrophils from the bone marrow to replace those consumed in inflammatory reactions. Recombinant G-CSF (rG-CSF) is used clinically to stimulate bone marrow recovery after routine cancer chemotherapy and bone marrow transplantation. The use of rG-CSF in cancer patients relies on the data showing that this cytokine does not enhance tumor growth [1]. However, several reports have shown that exogenous G-CSF may increase invasiveness of tumor cells [2], [3], suggesting a potential role of G-CSF in tumor growth and metastasis. Recently, an increasing number of reports have described G-CSF production by non-hematopoietic malignancies, including carcinomas of the lung [4], [5], bladder [6], stomach [7], and uterine cervix [8], [9]. However, the biologic significance of G-CSF production by tumor cells is not understood.

Here, we report a case of squamous cell carcinoma of the head and neck (SCCHN) producing G-CSF and characterized by marked leukocytosis. G-CSF production by the tumor was determined by immunohistochemistry (IHC), and furthermore, we also investigated the expression of molecules concerning the acquisition of more malignant tumor phenotypes.