CD147 And VEGF Expression In Advanced Renal Cell Carcinoma And Their Prognostic Value

Aim:To investigate the clinicopathologic characteristics of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN/CD147) and Vascular Endothelial Growth Factor (VEGF) expression in advanced renal cell carcinoma (RCC), and to evaluate the clinical significance of these two markers in the prognosis of advanced RCC.Background: Renal cell carcinoma (RCC) generally arises in the epithelium of the proximal tubule. Approximately 80% are of clear cell histology and 15% are papillary. It occurs predominantly in patients over the age of 50 and is more common in men than women . Early detection and treatment of RCC is associated with an improved outcome. In its early stages, the disease can be successfully treated by radical nephrectomy or even nephron-sparing surgery. However, many patients present with advanced or unresectable disease, and up to 30% of patients treated by nephrectomy for localized disease will relapse. The 5-year survival rate for stage III patients (with involvement of the renal vein or inferior vena cava and/or regional nodes) is little over 40%, and survival falls to lower than 11% for patients with locally advanced disease and/or distant metastases . Therefore, it is of great significance to search for sensitive and specific markers that can provide valuable information for the early diagnosis of RCC.Recently, it has been demonstrated by a number of clinical reports that the biological behavior and prognosis of RCC could be greatly different among the patients at the same stages and with histological types or differentiation grades. A number of biomarkers have been found to be involved in its development and progression.Among these markers, extracellular Matrix Metalloproteinase Inducer (EMMPRIN, also known as CD147) has no basal expression in normal tissues but is abundant in malignant tumor tissues, facilitating tumor metastasis . CD147 may thus induce tumor invasion/metastasis by activating MMPs production, modulating cell-substrate, and adhesion processes. The roles of CD147 in tumor invasiveness have been confirmed immunohistochemically in several types of cancer cells, including astrocytomas and melanomas . Moreover, their expression is reported to correlate with the clinical prognosis of patients with breast carcinoma and other types of cancers. Angiogenic factors, such as vascular endothelial growth factor (VEGF), are key mediators in the angiogenesis and invasion of RCC. However, it is not known yet whether these tumor biomarkers that are detectable in tissues are valuable in predicting the RCC prognosis. In this study, we have investigated the prognostic role of CD147 and VEGF by immunohistochemical staining in a series of advanced RCC patients.Materials and methods: CD147 and VEGF expression in paraffin-embedded specimens gathered from 53 patients with advanced RCC and 12 healthy controls were detected by the method of immunohistochemistry. The Spearman correlation was calculated between the expression levels of CD147 and VEGF in advanced RCC tissues. The association of CD147 and VEGF expression with the clinicopathologic features and with the prognosis of advanced RCC was subsequently assessed.Statistical analysis: The software of SPSS version13.0 for Windows (SPSS Inc, IL, USA) and SAS 9.1 (SAS Institute, Cary, NC) was used for statistical analysis. Continuous variables were expressed as X±s. Statistical analysis were performed with Fisher's exact test for any 2×2 tables,Pearsonχ2 test for non- 2×2 tables, chi-square trend test for ordinal datum, Kaplan-Meier and Cox Regression methods for the question of survival analysis. Differences were considered statistically significant when p was less than 0.05.Result: CD147 and VEGF were positively expressed in 47/53 (88.7%) and 45/53 (84.9%) of patients with advanced RCC, respectively. Positive expression of CD147 and VEGF was significantly correlated with TNM stage and symptom of advanced RCC. A significant correlation was found between the expression of CD147 and VEGF in advanced RCC (r=0.629, p=0.04). Additionally, tumor CD147 expression and tumor VEGF expression were significantly associated with the prognosis of advanced RCC patients. The survival rate of the patients with CD147-/VEGF- expression was the lowest (p<0.01), and conjoined expressions of CD147-/VEGF- and CD147+/VEGF+ were independent prognostic indicators of advanced RCC (both p<0.01).Conclusion: 1,The expression of CD147 and VEGF in advanced RCC upgrade to highest level, they may be an important feature of advanced RCC. 2,CD147 and VEGF is closely related with invasion and metastasis ability of the Renal cell carcinoma,is significant to assessing the Renal cell carcinoma malignant degree and judgment of prognosis. 3,A combined detection of CD147/VEGF co-expression is related with the clinical pathology feature of advanced RCC, is beneficial to deep understanding of the development process of the tumor, may benefit us in prediction of the prognosis of advanced RCC. 4,CD147 and VEGF expression have relativity on the function mechanism in RCC. Following the advanced research of molecular biology mechanism , it is hoped that new drug would be invented in the future, and raise the survival rate of the patients.