Clinicopathologic and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma
Clinicopathologic and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma
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DOI：
10.1002/cncr.21127
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发表时间：
2005-06-15
期刊：
影响因子：
6.2
通讯作者：
Belldegrun, AS
中科院分区：
文献类型：
--
作者：
Lam, JS;Shvarts, O;Belldegrun, AS
背景肾细胞癌（RCC）患者原发肿瘤组织学坏死的存在已被认为是生存的重要预测因素。作者研究了肿瘤坏死与其他临床病理因素的关系，这些因素是RCC患者重要的预后指标。对311例接受RCC治疗的患者的记录进行了基本临床病理信息的评价，包括TNM分类、核分级、东部肿瘤协作组（ECOG）体能状态（PS）、疾病复发和生存。记录原发肿瘤组织学坏死的存在和程度，并与临床病理因素、碳酸酐酶IX和Ki-67表达、疾病复发和生存率相关。与无坏死的肾细胞癌患者相比，肾细胞癌患者原发肿瘤中存在坏死与较高的T分类相关（P < 0.0001），淋巴结疾病的存在（P = 0.009），转移的存在（P < 0.0001），高级别（P < 0.0001），平均肿瘤大小较大（P < 0.0001），ECOG PS评分1（P = 0.007），加州大学洛杉矶分校综合分期系统（UISS）类别较高Ki-67阳性表达明显高于正常对照组（P < 0.0001）。原发肿瘤的坏死程度与淋巴结疾病的存在有关（P = 0.009）和转移的存在T分级越高，其阳性率越高（P < 0.0001）（（sigma = 0.31，P < 0.0001），ECOG PS较差（sigma = 0.18，P = 0.002），更高级别（σ = 0.33，P < 0.0001），肿瘤尺寸较大（σ = 0.40，P < 0.0001）、较高的UISS分类（T = 0.37，P < 0.0001）和较高的Ki-67染色（σ = 0.32，P < 0.0001）。与原发肿瘤无坏死的患者相比，原发肿瘤有坏死的患者的5年疾病特异性生存率较低（36% vs. 75%; P < 0.0001）。多因素分析显示T分级（P < 0.0001）、远处转移（P < 0.0001）和ECOG PS（P < 0.0001）是DSS的独立预测因子，而坏死的存在不是DSS的独立预测因子（P = 0.1100）。局部和转移性疾病的亚分层表明，坏死的存在是局部（P = 0.025），但不是转移性（P = 0.44），疾病患者生存的独立预测因子。坏死程度不是生存率的独立预测因子（P > 0.05）。原发肿瘤有坏死的患者与无坏死的患者相比，5年无复发率较低（62%对92%，P < 0.0001）。原发性肿瘤坏死的存在与不良预后因素相关，如高T分类、存在淋巴结疾病和转移、高级别、肿瘤大小大和ECOG PS差。发现坏死程度与淋巴结疾病和转移的存在相关，并与较高的T分类、较高的分级、较大的肿瘤大小、较差的ECOG PS和较高的UISS分类相关。这种组织学变异的存在是局部但非转移性疾病患者生存率较差的独立预测因素。此外，Ki-67表达作为一个有价值的替代标记物的存在下，组织学肿瘤坏死。(c)2005年美国癌症协会。
BACKGROUND. 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.METHODS. 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.RESULTS. 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 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 ((T = 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).CONCLUSIONS. 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. (c) 2005 American Cancer Society.