Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness.

Prognostic markers for renal cell carcinoma (RCC), such as patient symptoms, tumor stage, tumor size, and tumor grade, are useful for determining appropriate follow-up and selecting patients for adjuvant therapy. Histologic coagulative tumor necrosis, also reported to be a prognostic marker for RCC, has not previously been extensively described or investigated. Hence, the objective of the current study was to characterize tumor necrosis as a prognostic feature of RCC. The authors of the current study identified 3009 patients treated surgically for RCC between 1970 and 2002 from the Mayo Clinic Nephrectomy Registry (Rochester, MN). Associations of tumor necrosis with clinical, laboratory, and pathologic features were examined with chi-square, Fisher exact test, and Wilcoxon rank-sum tests. Cancer-specific survival was estimated with the Kaplan-Meier method, and associations with outcome were assessed with Cox proportional hazard models. Tumor necrosis was present in 690 of 2445 (28%) clear cell, 196 of 421 (47%) papillary, and 28 of 143 (20%) chromophobe RCCs. The risk ratio for death from RCC in patients with necrotic compared with non-necrotic tumors was 5.27 (95% confidence interval [CI]: 4.56-6.09; P < 0.001) for clear cell, 4.20 (CI: 1.65-10.68; P < 0.001) for chromophobe, and 1.49 (CI: 0.81-2.74; P = 0.199) for papillary RCC. The survival difference for clear cell RCC persisted even after multivariate adjustment for tumor stage, size, and grade (risk ratio 1.90; P < 0.001). Histologic coagulative tumor necrosis is an independent predictor of outcome for clear cell and chromophobe RCC, and it should be routinely reported and used in clinical assessment.

Sengupta S ，Lohse CM ，Leibovich BC ，Frank I ，Thompson RH ，Webster WS ，Zincke H ，Blute ML ，Cheville JC ，Kwon ED ... -  《CANCER》

pT1 clear cell renal cell carcinoma: a study of the association between MIB-1 proliferative activity and pathologic features and cancer specific survival.

The majority of patients with pT1 clear cell renal cell carcinoma (RCC) are cured with nephrectomy. However, a few patients will die of RCC. In several studies, MIB-1 proliferative activity was identified as an independent predictor of survival in patients with RCC. The objective of the current study was to examine MIB-1 proliferative activity in a large series of patients with pT1 clear cell RCC who were treated uniformly with radical nephrectomy, and to examine the association between proliferative activity and cancer specific survival in a multivariate model incorporating tumor size, nuclear grade, and tumor necrosis. Patients with solitary pT1 clear cell RCC who underwent radical nephrectomy between 1970-1997 were eligible for the current study. For each of the 40 patients who died of RCC, a stratified random sample of at least 3 year-matched patients who still were alive or had died of other causes at the time of last follow-up was selected. Patient age at nephrectomy, patient gender, tumor size, nuclear grade, and tumor necrosis were evaluated, and the MIB-1 proliferative activity was assessed using digital image analysis. Univariate and multivariate Cox proportional hazards models were fit to assess the features associated with cancer specific survival. The associations between MIB-1 proliferative activity and pathologic features were assessed using the Wilcoxon rank sum test. The mean MIB-1 value for those patients who died of clear cell RCC was 6.5% compared with 3.6% for those patients who died of other causes or were still alive at the time of last follow-up. Patients whose tumor had an MIB-1 proliferative activity > o r = 5.0% were more than twice as likely to die of RCC than patients whose tumors had a MIB-1 activity < 5% (P = 0.02). However, after adjusting for tumor size, nuclear grade, and necrosis, MIB-1 proliferative activity was not found to be associated significantly with cancer specific survival. There was a significant association between MIB-1 proliferative activity and tumor size, nuclear grade, and necrosis. After adjusting for tumor size, nuclear grade, and necrosis, MIB-1 proliferative activity was not found to be an independent predictor of outcome in patients with pT1 clear cell RCC who were treated with radical nephrectomy. There was a significant association between MIB-1 and other well established pathologic prognostic features of pT1 clear cell RCC.

Cheville JC ，Zincke H ，Lohse CM ，Sebo TJ ，Riehle D ，Weaver AL ，Blute ML ... -  《CANCER》

Long-term survival of patients with unilateral sporadic multifocal renal cell carcinoma according to histologic subtype compared with patients with solitary tumors after radical nephrectomy.

Dimarco DS ，Lohse CM ，Zincke H ，Cheville JC ，Blute ML ... -  《-》

Ki-67 and coagulative tumor necrosis are independent predictors of poor outcome for patients with clear cell renal cell carcinoma and not surrogates for each other.

Tollefson MK ，Thompson RH ，Sheinin Y ，Lohse CM ，Cheville JC ，Leibovich BC ，Kwon ED ... -  《CANCER》

Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials.

The objective of the current study was to develop an algorithm to predict progression to metastases after radical nephrectomy for patients with clinically localized renal cell carcinoma (RCC) to allow stratification of patients for potential adjuvant therapy trials. The authors identified 1671 sporadic patients with clinically localized, unilateral clear cell RCC who underwent radical nephrectomy between 1970 and 2000. The clinical features examined included age, gender, smoking history, recent onset hypertension, performance status, and presenting symptoms. The pathologic features examined included surgical margins, tumor stage, regional lymph node status, tumor size, nuclear grade, histologic tumor necrosis, sarcomatoid component, cystic architecture, and multifocality. Metastases free survival was estimated using the Kaplan-Meier method. A multivariate Cox proportional hazards regression model was fit to determine associations between the clinical and pathologic features and distant metastases. The median follow-up was 5.4 years (range, 0-31 years). Metastases occurred in 479 patients at a median of 1.3 years (range, 0-25 years) after nephrectomy. The estimated metastases free survival rates were 86.9% at 1 year, 77.8% at 3 years, 74.1% at 5 years, 70.8% at 7 years, and 67.1% at 10 years. Multivariate analysis showed that the following features were associated with progression to metastases: tumor stage, regional lymph node status, tumor size, nuclear grade, and histologic tumor necrosis (P < 0.001 for all). In patients with clear cell RCC, tumor stage, regional lymph node status, tumor size, nuclear grade, and histologic tumor necrosis showed statistically significant associations with progression to metastatic RCC. The authors present a scoring algorithm based on these features that can be used to predict disease progression after patients undergo radical nephrectomy for clinically localized clear cell RCC. Cancer 2003;97:1663-71.

Leibovich BC ，Blute ML ，Cheville JC ，Lohse CM ，Frank I ，Kwon ED ，Weaver AL ，Parker AS ，Zincke H ... -  《-》