Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer
Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer
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DOI：
10.1158/1078-0432.ccr-04-2019
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发表时间：
2005-05-15
影响因子：
11.5
通讯作者：
Signoretti, S
中科院分区：
文献类型：
--
作者：
Atkins, M;Regan, M;Signoretti, S
目的：肾癌对白细胞介素2 （IL-2）治疗的反应和患者生存与肿瘤组织学和碳酸酐酶IX （CAIX）表达相关。为了证实和扩展这些观察结果，我们检测了先前接受过IL-2治疗的肾癌患者病理标本中CAIX的表达。实验设计：用MN-75单克隆抗体对肾癌石蜡包埋组织切片进行免疫染色，观察其表达水平与组织学表现和临床结果的相关性。结果：66例患者获得组织标本；其中27例（41%）对基于il -2的治疗有反应。58个标本被评估为透明细胞，其中56个、33个和4个分别具有肺泡、颗粒和乳头状特征。根据Upton病理模型分为好、中、差预后组24例（36%）、31例（47%）、11例（17%）。41例（62%）标本CAIX高表达。27例应答患者中有21例（78%）有高表达CAIX的肿瘤，而39例无应答患者中有20例（51%）有高表达CAIX的肿瘤（优势比为3.3;P = 0.04）。中位生存期延长（P = 0.04）；仅在CAIX高表达者中可见5年。在病理预后中等的患者中，9名应答者均有高CAIX表达，而22名无应答者中有11名。单独病理预后良好或病理预后中等且CAIX较高的组中，27名应答者中有26名（96%）应答，39名无应答者中有18名（46%）应答（优势比为30；P < 0.01），中位生存期更长（P < 0.01）。结论：在接受il -2治疗的肾癌患者中，CAIX表达似乎是预后的重要预测因子，并可能增强病理标本中获得的预后信息。
Purpose: Renal cancer response to interleukin 2 (IL-2) therapy and patient survival has been correlated with tumor histology and carbonic anhydrase IX (CAIX) expression. In an effort to confirm and expand these observations, we examined CAIX expression in pathology specimens from renal cancer patients who had previously received IL-2 therapy.Experimental Design: Paraffin-embedded tissue sections of renal cancer were immunostained with the MN-75 monoclonal antibody to CAIX and expression levels were correlated with histologic findings and clinical outcome.Results:Tissue specimens were obtained from 66 patients; 27 of whom (41%) had responded to IL-2-based therapy. Fifty-eight specimens were assessed as clear cell, with 56, 33, and 4 having alveolar, granular, and papillary features, respectively. Twenty-four (36%), 31 (47%), and 11 (17%) were classified into good, intermediate, and poor prognosis groups according to the Upton pathology model. Forty-one specimens (62%) had high CAIX expression. Twenty-one of 27 (78%) responding patients had high CAIX expressing tumors compared with 20 of 39 (51%) nonresponders (odds ratio, 3.3; P = 0.04). Median survival was prolonged (P = 0.04) and survival > 5 years was only seen in high CAIX expressers. In patients with intermediate pathologic prognosis, all nine responders had high CAIX expression versus 11 of 22 nonresponders. A resultant group with good pathologic prognosis alone or with intermediate pathologic prognosis and high CAIX contained 26 of 27 (96%) responders compared with 18 of 39 (46%) nonresponders (odds ratio, 30; P < 0.01) and exhibited longer median survival (P < 0.01).Conclusions: CAIX expression seems to be an important predictor of outcome in renal cell carcinoma patients receiving IL-2-based therapy and may enhance prognostic information obtained from pathology specimens.