Platelet-derived Growth Factor Receptor-α as a Biomarker for Tongue Spindle Cell Carcinoma

Spindle cell carcinoma (SpCC) is a subtype of poorly differentiated squamous cell carcinoma, and comprises a biphasic mixture of epithelial and mesenchymal cells. SpCC is a rare aggressive cancer, with a dismal prognosis. Furthermore, its characteristics remain unclear, complicating treatment for this malignancy. Developing specialized treatment strategies for SpCC that are different from traditional approaches for conventional squamous cell carcinoma is essential for obtaining good clinical outcomes.

Our previous report documented the presence of platelet-derived growth factor receptor alpha (PDGFRα)-expressing mesenchymal stem/stromal cells (MSCs) in the cancer mass of recurrent SpCC of the tongue. PDGFRα-positive cells identified as cancer-associated fibroblasts are involved in the fate of epithelial-mesenchymal transition in SpCC. In this study, we analyzed the distribution patterns of immunopositive signals for MSC markers including PDGFRα in tissue sections via immunostaining.

Immunohistological analysis showed an expansion of PDGFRα and other MSC marker-positive cells within the cancer fields. MSCs were adjacent to cancer epithelial marker EpCAM-positive cells. Some EpCAM-positive cell populations surrounded by cancer-associated fibroblasts were immunopositive for MSC markers including PDGFRα.

MSC expansion was observed in cancer areas containing EpCAM-positive cells, implying that MSCs, especially PDGFRα-positive MSCs, may serve as cancer niche elements involved in epithelial-mesenchymal transition. Additional studies focusing on PDGFRα pharmacological targeting in SpCC will contribute to understanding of this tumor biology and developing new strategies for treating SpCC.