Genotypic and phenotypic characterization of the histoblood group ABO(H) in primary bladder tumors.

The ABO(H) histoblood group genes have been mapped by linkage analysis to 9q34.1-34.2, an area of common deletions in bladder cancer. Lack of ABO(H) antigen expression in bladder tumors is a frequent and well-documented event. In bladder neoplasms the loss of A and B transferase activity is due to down-regulation of the ABO gene transcripts. Our study was undertaken in order to determine the presence of structural alterations of the ABO(H) gene-encoding locus in primary bladder tumors, to estimate the extent of allelic deletions and to characterize further the pattern of histoblood group antigen expression. Fifty-three primary bladder tumors were analyzed by immuno-histochemistry (IHC) using a panel of well-characterized antibodies and fresh frozen tissue sections. Normal and tumor DNA also were analyzed by PCR coupled with restriction enzyme analysis in order to establish the ABO genotype. Results obtained from these analyses were then compared to allelotyping data at the 9q34.1-4 region by Southern blotting. IHC data showed undetectable levels of antigen expression on neoplastic cells in 59% of informative cases. PCR-based genotypic results revealed allelic losses in 27% of heterozygous cases. Four of the 16 pheno- and/or genotypically altered cases (25%) presented loss of heterozygosity at D9S10 or D9S7 loci. Our data indicate that the lack of ABO antigen expression in certain bladder tumors is due to the allelic loss of the ABO glycosyltransferase-encoding genes and that in some of these tumors the loss involves the surrounding chromosomal region at 9q34.1-4.