The Expression And Significance Of PTEN And P38 MAPK In Benign And Malignant Prostatic Lesions

Background and Objective:In china, prostate cancer (PC) is the most common malignant neoplasm in rinary system. The proportion of prostate cancer is 9.7% in male malignant carcinoma and this proportion in developed countries is 15.3%, however, in developing countries the date is 4.3%. In America, the incidence of prostate cancer is about China's 90 times, but the mortality was China's 26 times. In general, domestic fatality rate is higher. The key of reducing the mortality lies in the early diagnosis and early treatment. Unfortunately, the natural course of prostate cancer is long. In addition, the clinical symptom is concealing and the domestic medical condition restricts the opportunity of screening for everyone. Many patients were discovered in late already. For the past few years, in some cities cancer incidence report shows that prostate cancer incidence becomes higher. So how to achieve inchoate discovery, early diagnosis and early treatment is significantly crucial. PTEN (Phosphatase and tensin homologydeleted On Chromosome ten) and p38MAPK (p38 mitogen-activated proteinkinases) have association with the development of many kinds of malignant tumors, which are tumor markers discovered in recent years. With reference to normal prostate tissue, researching the different expression of PTEN protein and p38 p38MAPK kinase in benign and malignant prostatic lesions, we want to disscuss the clinical significance of PTEN protein and p38MAPK kinase in the malignant transformation of prostatic epithelium, in order to offer a index for clinically early diagnosis and monitoring prostatic intraepithelial neoplasia (PIN) and preventing the malignant transformation from PIN to PC.Materials and Method:A total of 86 patients from department of urology, second hospital of Tianjin medical university, containing 20 cases of benign prostatic hyperplasia (BPH),20 cases of prostatic intraepithelial neoplasia (PIN) and 46 cases of prostatic carcinoma (PC), with accession from June 2005 through February 2010, were included in this study. The average age of three groups is (62.85±15.85), (64.35±8.92) and (66.26±9.55). No demonstrable difference was found in average age. SABC immunohistochemical analysis was used to determine the expression levels of PTEN and p38 in 20 cases of BPH,20 cases of PIN and 46 cases of PC. According to the whitmore-Jewett stage classification and the grade classification of Gleason scales, these samples could be classified into A+B 28 cases, C+D 18 cases; G1 (2-4 scores) 11 cases, G2 (5-6 scores) 20 cases, G3 (7-10 scores) 15 cases. In addition, we collected 2 normal prostate tissues as negative control from the corpses of the Department of anatomy, Tianjin medical university. Staining steps were carried out according to kit instructions, and we choose positive breast cancer histological section as positive control, with PBS replaced the antibody as negative control. The results were observed by light microscope, and buffy particles in cells were considered as positive cases. SPSS 16.0 software application was used for all analysis and statistical significance was defined as P values less than 0.05.Results:(1) PTEN is mainly distributed in the secretary cell of the normal prostate tissue. The expression of PTEN was the highest in BPH and significantly higher in PIN compared to PC (P<0.01), and the three groups showing significant difference (P<0.001). The expression of PTEN in PC was significant difference in clinical classification and pathological grade (P<0.01). In addition, PTEN protein expression in prostatic carcinoma was negatively correlated with tumor stage and histological grade (r=-0.352,-0.653, P<0.05); (2) p38 is less distributed in the normal prostatic glandular epithelium basal cell and scattered in the secretary cell of prostate cancer tissue, while, it is mainly distributed in the glandular epithelium basal cell of BPH and glandular epithelium cell in PIN. The expression of p38 was the highest in PC and significantly higher in PIN compared to BPH (P<0.001), and the three groups showing significant difference also (P<0.001). The expression of p38 in PC was significant difference in clinical classification and pathological grade (P<0.05). In addition, p38 expression in prostatic carcinoma was positively correlated with above features (r=0.298,0.596, P<0.05); (3) There was a negative correlation between PTEN and p38 expression in benign ang malignant prostatic lesions (r=-0.602, P<0.01).Conclusion:(1) This study suggests that PTEN protein is positive expression in normal prostate tissue, while expression intensity level becomes lower and lower among three groups (BPH,PIN,PC), showing significant difference between any two groups (P<0.01); (2) p38 is less distributed in the normal prostatic glandular epithelium basal cell, while expression intensity level becomes higher and higher among three groups, showing significant difference between any two groups (P<0.001); (3) PTEN protein expression in prostatic carcinoma was negatively correlated with tumor stage, and histological grade(r=-0.352,-0.653, P<0.05), while p38 expression was positively correlated with the above features(r=0.298,0.596, P<0.05); (4) There was a negative correlation between PTEN and p38 expression(r=-0.602,P<0.01) in benign and maligment prostatic lesions. PTEN may have cooperation with p38 in the process of molecular regulation of PC via synergistic actions, preventing the occurrence and development of prostate cancer. Low PTEN protein expression and elevated activation of p38 are involved in the malignant transformation of prostatic epithelium and may play a great role in the genesis and development of prostatic tumor.