RON, ROR1 and SUSD2 expression in tissues of endometrial carcinoma patients. Clinicopathological and prognostic implications

Introduction: Endometrial carcinoma is now considered a common female gynecologic cancer with increasing incidence, with 13-25% of patients being still liable to recurrence and metastasis, which needs further studies to detect novel targets and new therapies. The aim of the study was evaluate tissue expression of RON, ROR1 and SUSD2 in endometrial carcinoma and atypical endometrial hyperplasia using immunohistochemistry and correlate their expression with clinical, patho-logical and prognostic parameters of patients. Material and methods: We included samples from 100 patients with en-dometrial carcinoma. Sections from paraffin blocks were stained with RON, ROR1 and SUSD2 using immuno-histochemistry. Correlations between marker expression, clinicopathological features and prognostic samples were evaluated. Results: Upregulation of RON and ROR1 and downregulation of SUSD2 expression were found in endome-trial carcinoma more than atypical endometrial hyperplasia (p < 0.001). High RON and ROR1 expression levels were significantly associated with high grade (p < 0.001), presence of lymph node metastases (p = 0.003), distant metastases (p = 0.009), advanced International Federation of Gynecology and Obstetrics stage (p = 0.002), poor response to therapy (p = 0.046), and lower recurrence-free survival (RFS) rate (p = 0.002), progression-free survival (PFS) rate (p = 0.008), distant metastasis-free survival (DMFS) rate (p = 0.019) and overall survival rate (p < 0.001). Low SUSD2 expression was significantly associated with older patient age (p = 0.002), large tumor size (p = 0.003), high grade (p = 0.005), presence of adnexal invasion (p = 0.023), presence of lympho-vascular invasion (p = 0.021), extent of myometrial in-vasion (p = 0.002), lower RFS rate (p = 0.008), lower PFS rate (p = 0.023), and lower DMFS rate (p < 0.001). Conclusions: Upregulation of RON and ROR1 and downregulation of SUSD2 lead to promotion of endometrial can-cer cell proliferation, migration, epithelial-mesenchymal transition, and invasion.