Abstract
BackgroundProstaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer.MethodsWe analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3.ResultsEP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells.ConclusionsEP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy.
Highlights
With about 320,000 new cancer cases in 2012, endometrial cancer (EC) becomes the fifth most common tumor, following breast, colorectum, cervix uteri, and lung cancer
E2 (PGE2) receptor 3 (EP3) seems to play a crucial role in endometrial cancer progression
The highest expression was in G3, while the lowest expression was in G1
Summary
With about 320,000 new cancer cases in 2012, endometrial cancer (EC) becomes the fifth most common tumor, following breast, colorectum, cervix uteri, and lung cancer. It represents 4.8% of cancer in women worldwide and is the most frequent gynecological carcinoma in developed regions [1]. Estrogen receptors (ER), mediating the effect of estrogen, play a key role in differentiation and invasion of EC [6]. Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer
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