Atkins Michael, Regan Meredith, McDermott David, Mier James, Stanbridge Eric, Youmans Amanda, Febbo Philip, Upton Melissa, Lechpammer Mirna, Signoretti Sabina
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Clin Cancer Res. 2005 May 15;11(10):3714-21. doi: 10.1158/1078-0432.CCR-04-2019.
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.
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.
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).
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.
肾癌对白细胞介素2(IL-2)治疗的反应及患者生存率与肿瘤组织学和碳酸酐酶IX(CAIX)表达相关。为了证实并拓展这些观察结果,我们检测了曾接受IL-2治疗的肾癌患者病理标本中的CAIX表达。
用针对CAIX的MN-75单克隆抗体对肾癌石蜡包埋组织切片进行免疫染色,并将表达水平与组织学发现及临床结果相关联。
从66例患者获取了组织标本;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型,分别有56个、33个和4个具有肺泡状、颗粒状和乳头状特征。根据厄普顿病理模型,24例(36%)、31例(47%)和11例(17%)被分为预后良好、中等和较差组。41个标本(62%)有高CAIX表达。27例有反应患者中的21例(78%)肿瘤CAIX表达高,而39例无反应者中有20例(51%)如此(优势比,3.3;P = 0.04)。中位生存期延长(P = 0.04),且仅在高CAIX表达者中观察到生存期>5年。在病理预后中等的患者中,所有9例有反应者CAIX表达高,而22例无反应者中有11例如此。单独病理预后良好或病理预后中等且CAIX高表达的组合组中,27例有反应者中有26例(96%),而39例无反应者中有18例(46%)(优势比,30;P < 0.01),且中位生存期更长(P < 0.01)。
CAIX表达似乎是接受基于IL-2治疗的肾细胞癌患者预后的重要预测指标,且可能增强从病理标本获得的预后信息。