title: Prognostic markers for survival in patients with metastatic renal cell carcinoma treated with interleukin-2.
abstract: Interleukin-2 (IL-2)-based immunotherapy can induce antitumor responses in about 25% of patients with metastatic renal cell carcinoma (RCC). The limited effect and the severe side-effects of IL-2 have led us to perform a prognostic factor analysis. Twenty-four patients with metastatic RCC were treated with IL-2. Flow cytometry and immunohistology were used to determine DNA ploidy, HLA-II expression on tumor cells, and the presence of macrophages in the primary tumor. These variables were examined in relation to survival. The 4-year overall survival rate was 38%. Forty-six percent of the primary tumors were aneuploid. All tumors, except one, showed HLA-II expression and macrophage presence. A statistically significant correlation (r = 0.66, P = 0.002) was found between HLA-II expression and macrophage presence. Patients with high HLA-II expression had a lower 4-year survival (22% compared to 50%), as had patients with high macrophage presence (20% compared to 42%). Of note, patients characterized by both high HLA-II and high macrophage expression had the worst survival (13% compared to 50%). We concluded that DNA ploidy was not predictive for survival, whereas HLA-II expression and macrophage presence may represent valuable prognostic factors related to survival. The present data suggest that more of the patients with no or moderate HLA-II expression and/or no or moderate macrophage presence in the primary tumor could survive with persistence of their malignant disease after having received IL-2 immunotherapy, as compared to patients with both high HLA-II and high macrophage expression.
authors.affiliation: Department of Pathology, Leiden University Hospital, The Netherlands.
authors.forename: R L
authors.initials: RL
authors.lastname: van Bezooijen
authors.forename: H
authors.initials: H
authors.lastname: Goey
authors.forename: G
authors.initials: G
authors.lastname: Stoter
authors.forename: J
authors.initials: J
authors.lastname: Hermans
authors.forename: G J
authors.initials: GJ
authors.lastname: Fleuren
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006681:HLA-D Antigens / Q000032:analysis / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D006681:HLA-D Antigens; D007376:Interleukin-2