Abstract
Prostaglandin induced signalling is involved in different cancers. As previously described, the EP3 receptor expression decreases with increasing stage of cervical intraepithelial lesions (CIN). In addition, in cervical cancer EP3 is an independent prognosticator for overall survival and correlates with FIGO stages. Currently the role of Prostaglandin 2 receptor 2 (EP2) in CIN is unknown. The aim of this study was to analyse the expression of EP2 for potential prognostic value for patients with cervical dysplasia. EP2 expression was analysed by immunohistochemistry in 33 patient samples (CIN1–3) using the immune-reactivity scoring system (IRS). Expression levels were correlated with clinical outcome to analyse prognostic relevance in patients with CIN2. Data analysis was performed using non parametric Kruskal–Wallis and Spearman rank sum test. Cytoplasmic expression levels of EP2 correlated significantly (p < 0.001) with different grades of cervical dysplasia. Median EP2-IRS in CIN1 was 2 (n = 8), 3 in CIN2 (n = 9) and 6 in CIN3 (n = 16). Comparing regressive (n = 3, median IRS = 2) to progressive (n = 6, median IRS = 4) CIN2 cases the median IRS differed significantly (p = 0.017). Staining intensity (p = 0.009) and IRS (p = 0.005) of EP2 and EP3 correlate inversely. EP2 expression level significantly increases with higher grade of CIN and could qualify as a potential prognostic marker for the regressive or progressive course in CIN2 lesions. These findings emphasize the significant role of PGE2 signalling in CIN and could help to identify targets for future therapies.
Highlights
After breast, colorectal- and lung cancer, cervical cancer represents the fourth most common malignant tumour in women worldwide (Wallis 2014; Watson et al 2014).Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Approximately 500,000 women worldwide are newly diagnosed with cervical cancer per year. 260,000 women die from the disease each year (Gottlieb 2016; Jiang et al 2015; Landy et al 2016)
We compared the EP-2-IR-scores between the groups of CIN1-3 to analyse differences in EP2 expression levels
EP2 staining in CIN1 (b immune-reactivity scoring system (IRS) 2), CIN2 (c IRS 6) and CIN3 (d IRS 9). 200× magnification was used for picture b, c and d
Summary
500,000 women worldwide are newly diagnosed with cervical cancer per year. Incidence and mortality of cervical cancer correlates negatively with the Human Development Index and varies extremely in geographic contexts (Wentzensen 2016). Regarding Germany, 4500 women were diagnosed with cervical cancer in 2014 and 1500 of these patients died tumour associated (Zentrum fur Krebregisterdaten 2019). After the implementation of Pap smear screening, which detects precursor lesions of cervical epithelium, incidence dropped considerably (Hester et al 2019). The persistent infection with specific types of high-risk papillomaviruses is considered the main risk of intraepithelial neoplasia and especially in the development of cervical cancer (Schiffman et al 2011). The precursor lesions were formerly called cervical intraepithelial neoplasia (CIN) and ranged from CIN1 to CIN3 (Santesso et al 2016). In 2014 the histological WHO classification has been altered, and cervical intraepithelial neoplasia is referred to as squamous
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