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 risk of incidence between 10% and 12%. 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 human cancers. The homeobox (HOX) genes encode proteins which contain a 61 amino acid DNA-binding homeodomain and are involved in the transcriptional regulation of other genes during normal onto- and histogenesis. The class I HOX genes are organized in four clusters on different chromosomes in humans, with a high conservation in the order of the genes within each of these clusters. Re-expression of HOX gene products has been reported in a wide variety of neoplastically transformed cells and it seems quite likely that the HOX genes represent yet another class of oncofetal antigens involved in both normal development and carcinogenesis, as well as tumor progression. The expression pattern of three HOX gene products (HOX-B3, -B4, and -C6) was examined immunocytochemically in 11 human breast carcinoma (BC) tissues. In all observed BC cases, HOX-C6 was present in over 90% of the neoplastically transformed cells (+4) demonstrating a high grade (A and B) staining intensity. The same expression pattern was defined for the other two observed proteins (HOX-B3 and -B4; over 90% or +4 and a high grade staining intensity or A and B). Current treatment of BC encompasses the three "classic" modalities of therapy: surgical resection, radiotherapy, and chemotherapy. Although advances have been made, we still face great difficulties in the treatment of this deadly human neoplasm. Therefore, we are always seeking novel tumor associated antigens (TAAs), including oncofetal antigens, to use as molecular targets in cancer cell directed fourth modality immunotherapy.