The role of EP3-receptor expression in cervical dysplasia.

PURPOSE:Prostaglandin-mediated inflammatory reactions play a major role in different cancers. Prostaglandin E2-receptor 3 (EP3) expression correlates with FIGO stages in cervical cancer and has been shown to be an independent prognostic factor for overall survival. EP3 expression levels in cervical intraepithelial neoplasia (CIN) as the precursor lesion of cervical cancer are currently unknown. METHODS:EP3 expression was analyzed by immunohistochemistry in 124 patient samples (CIN 1-3 and healthy controls) using the IR-scoring system. Expression levels were correlated with clinical outcome to assess for prognostic relevance in patients with CIN 2. Data analysis was performed using Kruskal-Wallis and Mann-Whitney U test. RESULTS:EP3 expression levels significantly correlated with different grades of cervical dysplasia. Median EP3-IRS in healthy cervical tissue was 12 (n = 13) compared to 9 in CIN 1 (n = 38; p = 0.031 vs. healthy control), 6 in CIN 2 (n = 45; p < 0.001 vs. CIN 1) and 4 in CIN 3 (n = 28, p = 0.008 vs. CIN 2). The percentage of EP3 expressing cells in CIN 2 lesions was significantly lower in progressive than in regressive cases (mean percentage of EP3 positive cells in progress: 3.8%, n = 18; in regress: 9.3%, n = 20; p = 0.040). CONCLUSION:EP3 expression significantly decreases with higher grades of cervical intraepithelial neoplasia-which is in line with published IR scores in cervical cancer patients-and seems to be a prognostic marker for regression or progression of CIN 2 lesions. Our findings support the importance of the prostanoid pathway in cervical cancer and could help to identify targets for future therapies.

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