Expression Of EZH2 And PTEN In Prostate Cancer And Its Clinicopathologic Significance

Background and Objective:Human PcG (Polycomb Group) gene is a large gene family, it was first discovered in the process of embryo formation, and played a crucial role in embryonic development, cell cycle, blood cell formation and x chromosome inactivated regulation. EZH2 (enhancer of zeste homolog 2), also named ENX-1,is a key member of the PcG gene family, which was discovered as a new human gene that is the human homologue of the Drosophila protein Enhancer of Zeste in 1996. It expressed in early embryogenesis, and only restricted expressed in the latter stage of embryogenesis in central and peripheral nervous system and fetal hematopoietic system. EZH2 gene over-expressed in many tumors, such as prostate cancer and breast cancer, which was closely correlated with the occurrence and development of the tumor. Prostate cancer is the most frequent cause of death among all men cancer patients, and there are currently no effective therapeutic approaches for the metastatic prostate cancer in spite of advances in surgery and radiotherapy. This study aims to investigate the expression of EZH2 and PTEN protein in prostate cancer and benign prostatic hyperplasia. To explore the roles of EZH2 in the development and progression of prostate cancer, which might provide a new biological marker in the prostate cancer diagnosis, treatment and prognosis.Methods:Using tissue microarray, immunohistochemical staining to detect the expression of EZH2 and PTEN (phosphatase and tensin homology deleted on chromosome ten, PTEN) in 77 cases of prostate cancer and 30 cases of benign prostatic hyperplasia and to explore their various pathological features and clinical relationship.Results:EZH2 in prostate cancer-positive rate was 89.6%, in benign prostatic hyperplasia-positive rate was 66.7%, the difference between the two groups was statistically significant (P< 0.05). The expression of EZH2 in the cytoplasm of prostate cancers was significantly higher than that in the prostate hyperplasias (P< 0.01). There was little correlation of carcinomas for EZH2 expression with preoperative serum PSA level, preoperative serum cPSA level, patient age, Gleason grading, and clinical stage (P> 0.05). There was notable negative correlation of staining of prostate carcinomas between EZH2 and PTEN (rs=-0.373, P< 0.01).Conclusions:(1) The expression of EZH2 in prostate cancer was significantly higher than in benign prostatic hyperplasia, which might be involved in the formation of prostate cancers.(2) EZH2 was expressed in the nucleus of prostate cancer cells, but also accompanied the cytoplasm expression of majority prostate cancers. EZH2 staining in benign prostatic hyperplasia showed weak in the nucleus, which cytoplasm was almost no expression. We speculated that high expression of EZH2 in the cytoplasm of prostate cancer was closely related with the occurrence of prostate cancers.(3) We observed in the experiment that some of well-differentiated glands in prostate cancer were not stained by EZH2, while the surrounding irregular glands and diffuse tumor cells were stained better; Expression of the cytoplasm in prostate cancer cells correlated with Gleason grading. These suggested that EZH2 was related to tumor differentiation. To presume, expression of EZH2 related to the prognosis of prostatic carcinoma.(4) EZH2 was a transcriptional inhibitory factor. There was notable negative of correlation staining of prostate carcinomas between EZH2 and PTEN. We suggested that PTEN might been one of be suppressed anti-oncogenes by EZH2. PTEN was decreased in prostate cancer and might promote together cancer occurrence with EZH2.(5) The preoperative serum PSA and cPSA in prostate cancers were significantly higher than in patients with benign prostatic hyperplasia. They were all no significantly correlation with EZH2 in prostate cancers.They were as the commonly used indicator of prostate cancer for prostate cancer screening, differential diagnosis and postoperative review.(6) There was no significantly correlation of carcinomas for EZH2 expression with preoperative serum PSA level, preoperative serum cPSA level, patient age and clinical stage.