Abstract
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.
Highlights
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]
Apoptosis, and oncogenesis are associated with prostanoids, including prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), prostaglandin I2 (PGI2), prostaglandin F2 (PGF2) and thromboxane A27
Our study previously demonstrated that galectin-3 expression is correlated with a poor prognosis in the overall survival analysis of cervical cancer patients with no or low p16 expression[25]
Summary
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]. We previously reported that the EP3 receptor is an independent negative prognosticator for cervical cancer patients[11]. Altered galectin-3 expression is correlated to the stage of tumor progression in many types of carcinoma, such as colon, thyroid, breast and prostate cancer[20,21,22,23]. Our study previously demonstrated that galectin-3 expression is correlated with a poor prognosis in the overall survival analysis of cervical cancer patients with no or low p16 expression[25]. The aim of this study was to analyze EP2 expression in human squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the cervix in relation to overall survival and to investigate whether EP2 is associated with EP3 and galectin-3 regarding the survival of cervical cancer patients
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