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
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《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》
Clinicopathologic and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma.
The presence of histologic necrosis in the primary tumor of patients with renal cell carcinoma (RCC) has been suggested to be an important predictor of survival. The authors investigated the relation of tumor necrosis to other clinicopathologic factors known to be important prognostic indicators for patients with RCC.
The records of 311 patients undergoing treatment for RCC were evaluated for basic clinicopathologic information including TNM classification, nuclear grade, Eastern Cooperative Oncology Group (ECOG) performance status (PS), disease recurrence, and survival. The presence and extent of histologic necrosis of the primary tumors was recorded and correlated with clinicopathologic factors, carbonic anhydrase IX and Ki-67 expression, disease recurrence, and survival.
The presence of necrosis in the primary tumor of patients with RCC compared with patients with RCC without necrosis was associated with higher T classification (P < 0.0001), the presence of lymph node disease (P = 0.009), the presence of metastases (P < 0.0001), higher grade (P < 0.0001), greater mean tumor size (P < 0.0001), an ECOG PS score > or = 1 (P = 0.007), higher University of California-Los Angeles Integrated Staging System (UISS) category (P < 0.0001), and higher Ki-67 expression (P < 0.0001). The extent of necrosis in the primary tumor was associated with the presence of lymph node disease (P = 0.009) and the presence of metastases (P < 0.0001), and correlated with higher T classification (sigma = 0.31, P < 0.0001), poorer ECOG PS (sigma = 0.18, P = 0.002), higher grade (sigma = 0.33, P < 0.0001), greater tumor size (sigma = 0.40, P < 0.0001), higher UISS category (sigma = 0.37, P < 0.0001), and higher Ki-67 staining (sigma = 0.32, P < 0.0001). Patients with the presence of necrosis in the primary tumor demonstrated a lower 5-year disease-specific survival compared with patients without necrosis in the primary tumor (36% vs. 75%; P < 0.0001). Multivariate analysis demonstrated that T classification (P < 0.0001), distant metastases (P < 0.0001), and ECOG PS (P < 0.0001) were independent predictors of DSS, whereas the presence of necrosis was not (P = 0.1100). Substratification into localized and metastatic disease demonstrated that the presence of necrosis was an independent predictor of survival in patients with localized (P = 0.025), but not metastatic (P = 0.44), disease. The extent of necrosis was not an independent predictor of survival (P > 0.05). Patients with the presence of necrosis in the primary tumor had a lower 5-year disease recurrence-free rate compared with patients without the presence of necrosis (62% vs. 92%, P < 0.0001).
The presence of necrosis in the primary tumor was associated with adverse prognostic factors such as high T classification, presence of lymph node disease and metastases, high grade, large tumor size, and poor ECOG PS. The extent of necrosis was found to be associated with the presence of lymph node disease and metastases and correlated with higher T classification, higher grade, greater tumor size, poorer ECOG PS, and higher UISS category. The presence of this histologic variant was an independent predictor of poor survival in patients with localized, but not metastatic, disease. In addition, Ki-67 expression served as a valuable surrogate marker for the presence of histologic tumor necrosis.
Lam JS
，Shvarts O
，Said JW
，Pantuck AJ
，Seligson DB
，Aldridge ME
，Bui MH
，Liu X
，Horvath S
，Figlin RA
，Belldegrun AS
... -
《CANCER》
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