title: Immunohistochemical analysis of intratumoral heterogeneity of [131I]cG250 antibody uptake in primary renal cell carcinomas.
abstract: In previous studies, highly heterogeneous uptake of 131I-labelled chimeric monoclonal antibody G250 ([131I]cG250) in primary renal cell carcinomas has been observed (intratumoral differences > factor 100). In this study, we investigated a possible correlation between intratumoral antibody uptake and four immunohistochemically determined parameters: G250 antigen expression, blood vessel density, neovascularization and percentage of viable tumour cells. Whole tumour slices of four different tumours were cut into 1-cm3 cubes, and in each cube the [131I]cG250 uptake was determined. The correlation between [131I]cG250 uptake and each individual parameter was determined in a multiple regression analysis. Additionally, the data were reanalysed after introducing arbitrary cut-off values for each parameter. If a sample showed expression of a parameter above the introduced threshold value, this sample fulfilled one condition. Subsequently, the Pearson correlation coefficients were calculated from [131I]cG250 uptake and the number of fulfilled conditions (0-3). All tumour samples with high [131I]cG250 uptake [> 0.1% of the injected dose per gram (ID g(-1))] showed high antigen expression (> 50%). However, not all samples with high antigen expression displayed high uptake. A statistically significant correlation between [131I]cG250 uptake and antigen expression was found (beta = 0.44, 0.69 and 0.74) in three out of four tumours analysed. Of the other determined parameters, no consistent correlation with [131I]cG250 uptake was found; only the percentage of viable tumour cells correlated significantly in two out of four tumours (beta = 0.80 and 0.26). Calculation of the Pearson correlation coefficients showed a statistically significant correlation between [131I]cG250 uptake and an increased number of fulfilled conditions in all tumours, indicating that each of the individual parameters contribute to the uptake of [131I]cG250. These observations indicate that high antigen expression is a prerequisite for high antibody uptake. However, regional differences in antibody uptake within a tumour cannot be explained by antigen expression alone.
authors.affiliation: Department of Urology, University Hospital Nijmegen, The Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: Steffens
authors.forename: E
authors.initials: E
authors.lastname: Oosterwijk
authors.forename: N E
authors.initials: NE
authors.lastname: Zegwaart-Hagemeier
authors.forename: M A
authors.initials: MA
authors.lastname: van't Hof
authors.forename: F M
authors.initials: FM
authors.lastname: Debruyne
authors.forename: F H
authors.initials: FH
authors.lastname: Corstens
authors.forename: O C
authors.initials: OC
authors.lastname: Boerman
mesh_terms: D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D001345:Autoradiography; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D007680:Kidney Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins