title: 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-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.
authors.affiliation: Department of Oncology, Aarhus University Hospital, Denmark. fd@microbiology.au.dk
authors.forename: F
authors.initials: F
authors.lastname: Donskov
authors.forename: N
authors.initials: N
authors.lastname: Marcussen
authors.forename: M
authors.initials: M
authors.lastname: Hokland
authors.forename: R
authors.initials: R
authors.lastname: Fisker
authors.forename: H H T
authors.initials: HH
authors.lastname: Madsen
authors.forename: H
authors.initials: H
authors.lastname: von der Maase
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use*; D001707:Biopsy, Needle; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D002455:Cell Division; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology* / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000276:immunology / Q000627:therapeutic use; D019394:Ki-67 Antigen / Q000032:analysis* / Q000276:immunology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D007376:Interleukin-2; D019394:Ki-67 Antigen