In vivo assessment of the antiproliferative properties of interferon-alpha during immunotherapy: Ki-67 (MIB-1) in patients with metastatic renal cell carcinoma

Abstract

The aim of the present study was to investigate the in vivo antiproliferative effect of interferon alpha (IFN-α) 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-α-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 ≤ 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-α in vivo has only modest effect on tumour proliferation in patients with mRCC. Tumour Ki-67 (MIB-1) reactivity after I month of immunotherapy appears to be a significant predictor of patient survival. © 2004 Cancer Research UK.