Abstract 5355: Immunohistochemical variations in the expression of cancer stem cell and macrophage markers in primary and recurrent oral squamous cell carcinomas
Authors: Vira Darshni , Basak Saroj K. , Lai Chi , Fishbein Michael C. , Batra Raj K. , Wang Marilene B. , Srivatsan Eri S. 
Published: August 2012

Abstract
Head and Neck Squamous Cell carcinoma (HNSCC) is the fifth most common malignancy worldwide. Oropharyngeal squamous cell carcinoma (OSCC) is the most common subtype and the sixth most common cancer in the US, with 8,000-10,000 deaths/year. Despite the best available treatment options of surgery, radiation and chemotherapy, the five year survival rate is approximately 50%, indicating recurrence is a common phenomenon. Preliminary studies with HNSCC cell lines have indicated higher expression of cancer stem cell markers such as CD44 in the aggressive tumor cell lines. It has been shown that cancer stem cells play an important role in the development and maintenance of tumor cells and in distant metastases. Thus, the current study was undertaken to determine whether cancer stem cell markers can be detected in primary and recurrent OSCC samples. In addition, since immune response cells such as macrophages may also play an important role in disease progression, we analyzed the distribution of macrophages in primary and recurrent tumors. Immunohistochemical analysis was performed on tumor samples of patients with OSCC. Five samples from patients with primary tumors and five samples from patients with recurrent tumors were analyzed for CD 44, ALDH, and Bmi-1, cancer stem cell markers of HNSCC. In addition, all samples were stained with a monoclonal antibody, CD68, a marker for the detection of tumor-associated macrophages. In the primary tumor group, CD 44 and Bmi-1 stained diffusely throughout the specimens (&gt;90% staining), especially at the periphery of the lesions. ALDH stained strongly (&gt;90%) and diffusely in two of the primary samples, and scattered staining (3-5% of tumor cells) was seen in the other three primary samples. CD 68 stained mainly around tumor clusters but not between individual tumor cells. The recurrent tumors also showed a strong staining of CD 44 within the tumor, especially at the periphery. In contrast, staining of ALDH and Bmi-1 was relatively weak. Additionally, in contrast to the primary tumors, CD 68 staining was more diffuse, and especially strong between tumor cells, suggesting a migration of tumor-associated macrophages into the tumor. These features reflect the transitory and tumor-microenvironment dependent expression of biomarkers that mediate the aggressive tumor cell properties. In this context, the data suggest that infiltrating macrophages may be playing an important role in mediating both tumor recurrence, and the transition towards aggressive tumor cell phenotypes. Further studies will be required to determine the role of macrophage mediated modulation of aggressive properties (secreted cytokines versus cell-cell interactions) of oral squamous cell tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5355. doi:1538-7445.AM2012-5355