Identification of Podocalyxin As a Predictor of Metastasis of Renal Cell Carcinoma

• Main Authors: Yung-Ho Hsu, 許永和
• Other Authors: Tzuu-Shuh Jou
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/98879800143713155173

碩士 === 臺灣大學 === 臨床醫學研究所 === 95 === Background Renal cell carcinoma (RCC) arises from renal tubular epithelium and accounts for approximately 3% of adult malignancy. Distant metastasis is the main cause of mortality for this disease; however, no reliable biomarker available today is capable of predicting the chance of metastasis in afflicted RCC patients. Podocalyxin (PC), an anti-adhesion molecule that maintains an open filtration slit in podocytes of the renal glomerulae, has been recently implicated in the tumorigenesis and progression of a number of human cancers. We therefore set up to investigate whether PC can be a useful biomarker to predict metastasis and prognosis of RCC. Methods We obtained 398 paraffin-embedded tumor samples from RCC patients who had received nephrectomy between January 1995 and December 2004 in National Taiwan University Hospital. Totally 303 RCC patients with adequate clinical and pathological information were recruited into this study. We assessed PC expression status by immunohistochemistry (IHC) and computerized image analyzer for objective and quantitative analysis of IHC staining. Patient’s clinicopathological data, which were collected as baseline variables, were categorized into PC-negative and PC-positive subgroups. These clinical, pathological, and laboratory data were analyzed for their possible correlation to the outcome and survival of this cohort. Results Among 303 RCC tumor samples, 29 (9.6%) were PC-positive. Increasing PC expression was significantly associated with advanced grade tumors (p<0.001). Similar relationship was also observed in histological type of non-clear cell and clear cell type tumors (p=0.003), and metastasis found at surgery or during later follow-up to no metastasis patients (p<0.001). Kaplan-Meier analysis reveals that patients with PC-positive tumors have decreased metastasis-free survival (p<0.0001), disease-specific survival (p<0.0001) and overall survival (p<0.0001). Cox expression multivariable analysis of PC status (positive vs negative) in primary tumors showed hazard ratios of 3.59 (95% CI 1.51-8.53, p=0.004) for metastasis-free survival and 7.46 (95% CI 2.51-22.22, p<0.001) for disease-specific survival. Conclusions Podocalyxin over-expression is a poor prognostic predictor of renal cell carcinoma. It can serve as a useful biomarker to identify patients with increasing possibility of early metastasis and poor prognosis.