Immunocytochemical detection of the homeobox B3, B4, and C6 gene products in breast carcinomas

Breast cancer (BC) represents the most frequent neoplasm in women with a ri sk of incidence between 10% and 22%. The detection of tumor associated and oncofetal antigen re-expression in a variety of neoplastically transformed cell types has aided in the more precise diagnosis and prognostication of h uman cancers. The homeobox (HOX) genes encode proteins which contain a 61 a mino acid DNA-binding homeodomain and are involved in the transcriptional r egulation of other genes during normal onto- and histogenesis. The class I HOX genes are organized in foul clusters on different chromosomes in humans , with a high conservation in the order of the genes within each of these c lusters. Re-expression of HOX gene products has been reported in a wide var iety of neoplastically transformed cells and it seems quite likely that the HOX genes represent yet another class of oncofetal antigens involved in bo th normal development and carcinogenesis, as well as tumor progression. The expression pattern of three HOX gene products (HOX-B3, -B4, and -C6) was e xamined immunocytochemically in II human breast carcinoma (BC) tissues, In all observed BC cases, HOX-C6 was present in over 90% of the neoplastically transformed cells (++++) demonstrating a high grade (A and B) staining int ensity. The same expression pattern was defined for the other two observed proteins (HOX-B3 and -B4; over 90% ol ++++ and a high grade staining intens ity ol A and B). Current treatment of BC encompasses the three "classic" mo dalities of therapy: surgical resection, radiotherapy, and chemotherapy. Al though advances have been made, we still face great difficulties in the tre atment of this deadly human neoplasm. Therefore, we are always seeking nove l tumor associated antigens (TAAs), including oncofetal antigens, to use as molecular targets in cancer cell directed fourth modality immunotherapy.