The Expression And Significance Of PTEN, PAX-2 And PAX-8 In Endometrioid Carcinoma And Endometrial Intraepithelial Neoplasia

BackgrounThe study in endometrioid carcinoma and precancerous lesions of the uterus has important significance for the early diagnosis and treatment of endometrial cancer. We first know the concept of precancerous lesions when we need study precancerous lesions. It is classified to endometrial hyperplasia (simple or complex) without atypical hyperplasia and endometrial hyperplasia (simple or complex) with atypical hyperplasia according to the criterion of World Heathy Organization (WHO) classification. Atypical hyperplasia had a higher risk of progression to endometrial carcinoma and therefore has been considered to be precancerous lesions of uterine endometrial carcinoma. But unfortunately it is difficult to repeat it in pathological diagnosis. In recent years, some researchers have put forward the use of endometrial intraepithelial neoplasia (EIN) to represent the precancerous lesions of endometrial carcinoma, which have better repeatability and important clinical significance. But the molecular mechanism in the occurrence of EIN and endometrial cancer is not fully clear. So it is necessary to find some diagnostic biomarkers to assist the diagnosis of EIN and endometrial carcinoma and discuss its pathogenesis.Studies have shown that loss of function of the PTEN gene is closely related to the occurrence and development of endometrial cancer, but the loss of function of the PTEN gene can only explain a small part of the case. It is necessary to further explore the molecular mechanisms in endometrioid carcinoma and their precancerous lesions. Embryonic Pax-2 expression is required for development of the kidneys and thyroid, the uterus and oviducts in females, and the vas deferens and epididymis in males. In recent years, foreign studies suggested the loss of PAX-2 protein in endometrial cancer and precancerous lesions plays an important role. PAX-8 is also a transcription factor, which mainly expressed in the thyroid, kidney and female reproductive systems. But its role remains unclear in endometrial cancer and precancerous lesions.ObjectiveTo investigate expression and the role of PTEN, PAX-2 and PAX-8 protein in the differential diagnosis among normal endometrium, endometrial intraepithelial neoplasia (EIN) and endometrial carcinoma.MethodsThe PTEN, PAX-2 and PAX-8 expression were detected with immunohistochemistry in normal endometrium (n=15), EIN (n=15) and endometrial carcinoma (n=15). Each case was evaluated by two pathologists separately. EIN was defined according to the criteria proposed by Baak.ResultsImmunohistochemical results showed the PTEN expression was localized in the nuclei and cytoplasm of gland and stromal cells of endometrium. The PTEN expression was partly lost in EIN and endometrial carcinoma. The PTEN expression in EIN was significantly decreased compared that in normal endometrium (P<0.05). The PTEN expression in endometrial carcinoma was significantly decreased compared with that in EIN (P<0.05). The PAX-2 expression confined to the nuclei of gland in normal endometrium. The PAX-2 expression was partly lost in EIN and further reduced in endometrial carcinoma. The PAX-2 expression in EIN was significantly decreased compared that in normal endometrium (P<0.05). The PAX-2 expression in endometrial carcinoma was significantly reduced compared with that in EIN (P<0.05). The PAX-8 expressed in the nuclei of gland in normal endometrium and EIN. The endometrial carcinoma showed diffuse strong positive for PAX-8. However, there was no difference for PAX-8 expression among the normal endometrium, EIN and endometrial carcinoma (P>0.05).Conclusions1.The expression of PTEN gradually decreased from the normal endometrium, EIN to endometrial carcinoma.2.The expression of PAX-2 gradually decreased from the normal endometrium, EIN to endometrial carcinoma.3. Our findings suggest that the application of PTEN and PAX-2 might be useful to diagnose the EIN and endometrial carcinoma.4. PAX-8 protein can be used as an sensitive marker for endometrial epithelium.