Donskov F, Marcussen N, Hokland M, Fisker R, Madsen H H T, von der Maase H
Department of Oncology, Aarhus University Hospital, Denmark.
Br J Cancer. 2004 Feb 9;90(3):626-31. doi: 10.1038/sj.bjc.6601587.
The aim of the present study was to investigate the in vivo antiproliferative effect of interferon alpha (IFN-alpha) in patients with metastatic renal cell carcinoma (mRCC). Core needle biopsies of metastatic and/or the primary kidney cancer were obtained before interleukin-2 (IL-2)- and IFN-alpha-based immunotherapy in 34 patients and repeated after 5 weeks in 25 patients. Tumour proliferation was assessed by use of the anti-Ki-67 antibody MIB-1 and evaluated in multiple, random systematic sampled fields of vision. Ki-67 labelling index (LI) at baseline was median 13.6% (range 1.2-85.0) and median 10.6% (range 1.3-48.6%) at week 5 with a median overall decline of 15.2% (range -95 to +258%) from baseline to week 5. There was no difference between responding and nonresponding patients. Ki-67 LI at week 5 was significantly correlated to survival. Thus, median survival of patients with Ki-67 LI <or=10.6% at week 5 was 25.1 months compared to 11.5 months for patients with Ki-67 LI >10.6% (P=0.016). Baseline or change in Ki-67 LI did not correlate to survival. These data suggest that IFN-alpha in vivo has only modest effect on tumour proliferation in patients with mRCC. Tumour Ki-67 (MIB-1) reactivity after 1 month of immunotherapy appears to be a significant predictor of patient survival.
本研究的目的是调查α干扰素（IFN-α）对转移性肾细胞癌（mRCC）患者的体内抗增殖作用。在34例患者接受基于白细胞介素-2（IL-2）和IFN-α的免疫治疗之前，获取转移性和/或原发性肾癌的粗针活检样本，25例患者在5周后重复取样。通过使用抗Ki-67抗体MIB-1评估肿瘤增殖，并在多个随机系统取样视野中进行评估。基线时Ki-67标记指数（LI）中位数为13.6%（范围1.2 - 85.0），第5周时中位数为10.6%（范围1.3 - 48.6%），从基线到第5周总体中位数下降15.2%（范围 - 95至+258%）。应答患者和无应答患者之间无差异。第5周时的Ki-67 LI与生存率显著相关。因此，第5周时Ki-67 LI≤10.6%的患者中位生存期为25.1个月，而Ki-67 LI>10.6%的患者为11.5个月（P = 0.016）。Ki-67 LI的基线值或变化与生存率无关。这些数据表明，IFN-α在体内对mRCC患者的肿瘤增殖只有适度影响。免疫治疗1个月后的肿瘤Ki-67（MIB-1）反应性似乎是患者生存的重要预测指标。
