Purpose: We recently found that adipose differentiation-related protein (ADFP) is a potential diagnostic and prognostic biomarker for clear cell subtype renal cell carcinoma (RCC). To further evaluate the correlation between ADFP expression levels and clinicopathologic characteristics and patient outcome, we retrospectively examined patients with clear cell RCC. Experimental Design: A series of 432 consecutive patients with sporadic clear cell RCC who underwent nephrectomy between March 1986 and June 2004 were enrolled in the study. ADFP expression levels in the primary tumors and in 18 metastases were measured by real-time quantitative PCR. The clinicopathologic and prognostic data were collected, as well as the von HippelLindau disease (VHL) gene alteration status in selected cases. Results: ADFP expression was apparently high in cases without a symptomatic presentation, as well as in cases of low-stage, low-grade, or VHL alteration^positive clear cell RCC, whereas it was down-regulated in undifferentiated tumors with a spindle/pleomorphic component or metastatic lesions. Univariate analyses showed that high ADFP expression was associated with better cancer-specific survival and cancer-free survival. Further Cox multivariate analyses combined with the split-sample validation method showed that ADFP expression still remains an independent predictor for cancer-specific survival in all tumor stages and in advanced metastatic cases, whereas the predictive value of ADFP expression for cancer recurrence is rather weak. Conclusions: The ADFP expression may represent the tumor differentiation status, and the detection of the expression levels provides useful prognostic information for cancer-specific survival in patients with clear cell RCC.

Purpose: Vascular cell adhesion molecule 1 (VCAM1) is a cell surface glycoprotein implicated in various pathophysiologic conditions.We measured VCAM1 expression levels in tumor tissues and evaluated its significance and prognostic use in renal cell carcinoma (RCC). Experimental Design: We used real-time quantitative PCR to examine the VCAM1 expression levels of a total of 485 sporadic renal tumors, including 429 clear cell, 21 papillary, 17 chromophobe, 11 oncocytomas, and 7 collecting duct carcinomas. We retrospectively examined the relationship of this expression to various clinicopathologic variables and the von Hippel-Lindau alteration status. We evaluated its significance with respect to patient survival rates using the Cox regression model combined with the split-sample method. Results: Compared with normal kidney samples (n = 43),VCAM1 was significantly up-regulated in clear cell RCC and papillary RCC, whereas it was down-regulated in chromophobe RCC and oncocytoma. In clear cell RCC, VCAM1 expression levels were apparently high in patients asymptomatic at presentation and in patients with small tumor size, low-stage, low-grade, microvascular invasion^negative, and von Hippel-Lindau alteration-positive tumors. Univariate analyses showed that VCAM1 high expression is strongly associated with better outcomes in clear cell and papillary RCCs. Further, Cox multivariate analysis models combined with the split-sample method revealed that this association is significant only in cancer-free survival for patients with clear cell RCC after curative surgical resection. Conclusions: VCAM1 expression levels were found to be histologically subtype specific in renal tumors. Determination of theVCAM1 expression level as a biomarker can provide useful prognostic information for patients with clear cell RCC.

Renal cell carcinomas (RCCs) are morphologically and genetically heterogeneous tumors and present diverse clinical courses. We developed a scoring system using levels of gene expression to predict the outcome for clear cell RCC patients. We selected differentially expressed genes from the DNA microarray data of 27 clear cell RCCs; 16 were metastasis phenotypes and 11 were not. We compared the selected gene set with previously published data and identified 33 overlapping genes closely associated with patient outcome. We selected the 12 top-ranked genes and confirmed the level of expression using quantitative reverse transcriptase PCR. Multivariate Cox analysis revealed that 3 genes-vascular cell adhesion molecule 1 (VCAM1), endothelin receptor type B (EDNRB), and regulator of G-protein signaling 5 (RGS5)-were the most tightly associated with cancer-specific survival and that higher expression of the 3 genes correlated with better outcome. A formula for an outcome predictor was generated from integration of the measurements of the expression levels of the 3 genes. Multivariate Cox models combined with a split-sample cross-validation method in a cohort of 386 clear cell RCC patients demonstrated that the derived score for outcome prediction was an independent predictor in cancer-specific survival tests. The accuracy of the prediction of cancer death after nephrectomy was improved by the inclusion of this score in receiver operating characteristic analysis from multivariate logistic regression models, suggesting that a scoring system based on the expression levels of these 3 genes is useful in the prediction of survival for patients with clear cell RCC. ' 2008 Wiley-Liss, Inc.Key words: renal cell carcinoma; clear cell; microarray; real-time PCR; prognosis Renal cell carcinoma (RCC) is the most common malignant tumor of the adult kidney, accounting for 2-3% of human malignancies, and complete surgical resection is considered to be the only effective treatment for patients with localized RCC.1,2 Despite recent improvements in diagnostic imaging, 20-30% of patients are diagnosed to be in advanced stage, i.e., with local invasion or distant metastasis, at initial presentation. Moreover, tumors recur postoperatively in up to 50% of patients who undergo potentially curative surgery.

Maximal androgen blockade therapy is the standard endocrine treatment for advanced prostate cancer. We report here an unusual case of interstitial pneumonitis induced by bicalutamide and/or leuprorelin acetate treatment for metastatic prostate cancer.

ObjectiveC-reactive protein (CRP) is considered a useful serum marker for patients with RCC. However, its clinical utility in advanced metastatic renal cell carcinoma (AM-RCC), particularly in deciding whether to perform nephrectomy at the onset, is not well studied.Patients and methodsWe retrospectively evaluated 181 patients with AM-RCC, including 18 patients underwent potentially curative surgery, 111 underwent cytoreductive nephrectomy, and 52 received medical treatment only. CRP cutoff points were determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier and Cox regression analyses were used for survival tests.ResultsROC analysis suggested that grouping patients according to 3 CRP ranges was a rational model. Patients with highly elevated CRP (≥67.0 mg/L) presented remarkably poor prognosis despite treatment (nephrectomy or medical treatment only). Cox regression models demonstrated that risk factors of overall survival for patients who underwent nephrectomy were the CRP ranges defined in this study (≤18.0 mg/L, >18.0 and <67.0 mg/L, and ≥67.0 mg/L), ECOG PS (0, 1, and ≥2), and number of metastatic organ sites (0–1 and ≥2). The retrospective design is a limitation of this study.ConclusionOur study demonstrated that the serum CRP level is a statistically significant prognostic parameter for patients with AM-RCC. The data also indicated that pretreatment serum CRP level provides useful prognostic information that helps in deciding whether to perform initial nephrectomy for patients with AM-RCC.