We know that one of the main risk factors for cervical cancer is an infection with high-risk human papillomavirus (HR-HPV). Prostaglandins and their receptors are very important for the tumour growth and tumour-associated angiogenesis. Little is known about the expression of the Prostaglandin E receptor type 3 (EP3) or the Prostaglandin (PG)E2-EP3 signalling in cervical cancer, so the aim of the study was to analyse the expression of the EP3 receptor in cervical cancer and find prognostic factors in relation to survival; EP3 immunohistological staining of 250 cervical cancer slides was performed and analysed with a semi-quantitative score. The statistical evaluation was performed with Statistical Package for the Social Sciences (SPSS) to evaluate the staining results and the survival analyses of the cervical cancer cases. A significant difference was observed in EP3 expression in Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stadium I versus FIGO stadium II–IV cases. High expression of EP3 (IRS ≥ 1.5) in cervical cancer patients was correlated with poor prognosis in overall survival rates. Survival in adenocarcinoma (AC) of the cervix was lower than in squamous cell carcinoma (SCC). Cox regression analysis shows that EP3 is an independent prognosticator. In this study we could show that the membrane-bound prostaglandin receptor EP3 is an independent prognosticator for cervical cancer patient survival. Targeting the EP3 receptor seems to be an interesting candidate for endocrine therapy. Therefore, more research is needed on the influence of the receptor system and its influence on cervical cancer growth.
Recently our study identified EP3 receptor and galectin-3 as prognosticators of cervical cancer. The aim of the present study was the analysis of EP2 as a novel marker and its association to EP3, galectin-3, clinical pathological parameters and the overall survival rate of cervical cancer patients. Cervical cancer tissues (n = 250), as also used in our previous study, were stained with anti-EP2 antibodies employing a standardized immunohistochemistry protocol. Staining results were analyzed by the iRS scores and evaluated for its association with clinical-pathological parameters. H-test of EP2 percent-score showed significantly different expression in FIGO I-IV stages and tumor stages. Kaplan-Meier survival analyses indicated that EP3-negative/EP2-high staining patients (EP2 IRS score ≥2) had a significantly higher survival rate than the EP3-negative/EP2-low staining cases (p = 0.049). In the subgroup of high galectin-3 expressing patients, the group with high EP2 levels (IRS ≥2) had significantly better survival rates compared to EP2-low expressing group (IRS <2, p = 0.044). We demonstrated that the EP2 receptor is a prognostic factor for the overall survival in the subgroup of negative EP3 and high galectin-3 expressed cervical cancer patients. EP2 in combination with EP3 or galectin-3 might act as prognostic indicators of cervical cancer. EP2, EP3, and galectin-3 could be targeted for clinical diagnosis or endocrine treatment in cervical cancer patients, which demands future investigations.Cervical cancer is the fourth most common female cancer type worldwide with nearly half a million new cases annually. 83% of all cases occur in developing countries, whereas in developed countries only 3.6% of new cancer cases are cervical cancer 1 . One of the main risk factors for cervical cancer is a persistent infection with specific Human Papillomavirus (HPV), the high-risk papillomavirus (HR-HPV) 2 . HPV is manifested in nearly 99.7% of all cervical cancer patients 3 . Belonging to the papillomavirus family, HPV is a non-enveloped, small, double-stranded DNA virus 3-5 . More than 200 HPV genotypes have been characterized worldwide 6 . The sub-classification in high-risk and low-risk is important for the HPV infections of the genital tract 5 . Low-risk subtypes, such as HPV-6, HPV-11, HPV-26, HPV-40, HPV-42, are the cause of genital warts and non-malignant lesions 2,5 , whereas high-risk HPV types like HPV-16 and HPV-18 were identified in cervical and other anogenital cancers 2,5 .Tumor cell differentiation, apoptosis, and oncogenesis are associated with prostanoids, including prostaglandin E 2 (PGE 2 ), prostaglandin D 2 (PGD 2 ), prostaglandin I 2 (PGI 2 ), prostaglandin F 2 (PGF 2 ) and thromboxane A 2 7 . Prostaglandins are important for tumor progression and tumor-associated angiogenesis as Amano et al. described 8 . PGE 2 signaling is well-known for apoptosis inhibition, angiogenesis, metastatic formation, and tumor progression. The membrane-bound EP receptors specific for PGE 2 are G-protein coupled receptors and...
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