The Expression And Significance Of Pinl And CyclinD1in Clear Cell Renal Cell Carcinoma

ObjectiveRenal cell carcinoma (RCC) is the most common tumor arising from the cells in the lining of tubules in the kidney, accounts for about3%of all human cancers, second only bladder carcinoma. It is characterized by a lack of early-warning signs, which results in a high proportion of patients with metastases. Median survival for patients with metastatic disease is about13months. So there is a great need to find a new target in the inhibition of RCC proliferation. In renal cell carcinoma, clear cell renal cell carcinoma(CCRCC) accounts for about65%～80%.Oncogenesis is a multistep and multifactorial process in the geneticand epigenetic levels, which results in uncontrolled cell proliferation, transfor-mation and cell death. Phosphorylation of proteins on serine or threonine residues preceding pro-line(Ser/Thr-Pro) is an important signal mechanism controlling many cellular processes, such as cell cycle regulation, cell differentiation and proliferation. The conformation and function of phosphorylated Ser/Thr-Pro motifs are further regulated by the prolyl isomerase Pin1. The overexpression of Pin1is involved in the tumor development and progression. CyclinD1is a checkpoint of G1/S transition. Inhibition of CyclinD1causes cells arrest in G1phase, which suppresses tumor cells growth. Studies have demonstrated that CyclinD1was overexpressed in many tumors.In our study, the expressions of Pin1and CyclinD1in CCRCC and corresponding adjacent kidney tissues were detected by immunohistochemistry to explore the expression of Pin1and its relationships with CyclinD1in CCRCC, Their function in the CCRCC was further discussed.Material and MethodA total of102consecutive patients from department of urology, second hospital of Tianjin medical university, Tianjin institute of urology(64males and38females) with RCC undergoing nephrectomy and information complete, with accession from June2007through January2008, were included in this study. The median age was56years with arrange of30～81years. WHO grade:Ⅰ grade was in21cases, Ⅱ grade was in34cases, Ⅲ grade was in15cases. Robson clinical stage:Ⅰ stage was in20cases, II stage was in29cases, III stage was in14cases, IV stage was in7cases. Fifty normal tissue of>2cm domain beside tumor were recruited as eontrols. Tissue from70cases of RCC by immunohistochemical staining was assessed without knowledge of the Patient’s clinicopathological characteristics by two senior pathology doetor through double blind method.Pinl, CyclinDl were detected by immunohistochemistry S-P。Result determination:Pinl：The normal staining was in the nucleus; the overexpressed staining was in the nucleus and/or cytoplasm. A:The staining intensity was scorded as negative(0), weak(1), moderate(2)and strong(3); B:The number of cells stained was graded as follows:<25%(0),25%-49%(1),50%-74%(2),^75%(3) AxB, Grades≥3showed its overexpression.CyclinD1was a nucleus and(or) cytoplasm staining protein. Less than10%of tumor cells showed negative, and over10%of tumor cells showed positive.All the data were analyzed by SPSS3.1medical statistics software.X2-test was used to compare the clinicopathological characteristics with the expression of Pinl and CyclinD1. The statiscal significance was defined as P<0.05.The result1. Expression of Pinl and CyclinDl in CCRCC tissuesThe overexpression ratios of Pinl in adjacent kidney tissues of carcinoma and in renal cell carcinoma were11.43%and68.43%respectively. There was significant difference after X2-test(P<0.01). CyclinDl was rarely expressed in adjacent kidney tissues, and was mainly expressed in nucleus of the renal carcinoma cells. The positively expression ratios of CyclinDl in adjacent kidney tissues of carcinoma and in renal cell carcinoma were8.57%and62.75%respectively, showing significant difference (P<0.01)2. The relationship of Pinl and CyclinDl between expression and characteristics of clinical pathology in CCRCC.There was no significant correlation between the over expression of Pinl and age, gender, tumor size, pathology grade of patients. There was positive correlation between the expression of Pinl and clinical TNM classification(P<0.05). The kind of situation to Pin is the same to CyclinDl. All of102patients were followed up except2patients loss to follow-up and2patients died of other diseases. The rest of the98patients were analyzed that there was no significant correlation between the expression of Pin1and recurrence rate, five-year survival rate of patients.3. The correlation between expression of Pin1and cyclinD1in CCRCC50cases were positive expression of cyclinD1in70cases of CCRCC of over expression of Pin1,18cases were negative expression of cyclinD1in30cases of ovarian cancers of lower expression of Pin1. There was positive significant correlation between Pin1and cyclinD1in ovarian cancers.(P<0.01)Conclusion1. The level of Pin1in the tumor tissues is noticeably higher than that in the adjacent kidney tissues. The level of cyclinD1in the tumor tissues is noticeably higher than that in the adjacent kidney tissues.2. The over expression of Pin1protein and the express of CyclinD1protein was related to clinical TNM classification, but not related to age, gender, tumor size, pathology grade of patients.3. There was no significant correlation between the over expression of Pin1and recurrence rate, five-year survival rate of patients. There was no significant correlation between the over expression of CyclinD1and recurrence rate, five-year survival rate of patients, too.4. This study showed that Pin1level correlated with CyclinD1positively, which suggests that up-regulation of Pin1enhances the expression of CyclinD1, acting as an upsteam factor of CyclinD1. The abnormal expression of both may be public to participate in the development of CCRCC.