HIGH-FREQUENCY OF ALTERED HLA CLASS-I PHENOTYPES IN INVASIVE COLORECTAL CARCINOMAS

We analyzed the expression of HLA class I antigens in 78 tumor tissue samples obtained from patients diagnosed as having colorectal carcinom as. A broad panel of mAbs defining HLA monomorphic, locus-specific and allele-specific determinants was used. In addition, an antibody defin ing HLA-C locus-specific determinant (L31) was also tested. Previous r eports on these tumors indicated HLA class I losses of 30 to 40%,. At least 73% of the patients in the present study had a detectable HLA Cl ass I alteration, These altered HLA phenotypes were classified as tota l HLA loss (18%) (phenotype I); HLA-A locus-specific loss (9%) (phenot ype IIIa); HLA-B locus-specific loss (8%) (phenotype mb); HLA-A and B locus losses (2%) and HLA allelic losses (36%) (phenotype IV). We foun d no HLA-C locus losses. Autologous peripheral blood lymphocyte HLA cl ass I typing was always necessary to define phenotype IV, We also stud ied the CD3 zeta chain in tumor tissues to correlate possible changes in the CD3 signal transduction pathway with HLA alterations. The CD3 r atio was frequently altered, but this alteration could not be correlat ed with tumor HLA phenotypes, The high frequency of HLA class I losses in colorectal carcinomas suggests that this finding is a widespread p henomenon and may be required to escape T-cell recognition. It remains to be determined whether HLA expression is ''normal'' in the rest of the 27% of our patients.