Expression of erythropoietin and its receptor in oral squamous cell carcinomas

Erythropoietin (Epo) is a multi-functional growth factor that promotes cell proliferation, migration and survival, tumor angiogenesis, and tumor cell invasion and metastasis. Its diverse biological effects are mediated through its interaction with its erythropoietin receptor (EpoR). In this study, we examined the expression of Epo and EpoR in 60 specimens of oral squamous cell carcinoma (OSCC), 40 specimens of oral epithelial dysplasia (OED), 20 specimens of oral epithelial hyperkeratosis (OEH), and 10 specimens of normal oral mucosa (NOM) by immunohistochemistry. The Epo and EpoR labeling indices (LIs) in OSCC, OED, OEH, and NOM groups were calculated and compared between groups. The correlation between the expression of Epo or EpoR in OSCCs and clinicopathological parameters or survival of OSCC:patients was analyzed statistically to investigate the possible influence of Epo or EpoR on the progression and prognosis of OSCCs in Taiwan. Positive Epo or EpoR staining was mainly cytoplasmic. The mean Epo LI increased significantly from NOM (0%) through OEH (14 +/- 10%) and OED (45 +/- 24%) to OSCC samples (68 +/- 21%, p = 0.000). The mean EpoR LI also increased significantly from NOM (8 +/- 3%) and OEH (30 +/- 13%) through OED (53 +/- 27%) to OSCC samples (74 +/- 23%, p = 0.000). Statistical analysis showed a significant association of higher Epo or EpoR expression in OSCCs with the younger age of patients, the larger tumor size, the presence of lymph node metastases, and the more advanced clinical stages of OSCC. Our results suggest that the expression of Epo and EpoR is an early event in oral carcinogenesis in Taiwan. The Epo or EpoR LI in OSCC samples can predict the progression of OSCCs in Taiwan.