Immunocytochemical detection of homeobox B3, B4, and C6 gene product expression in lung carcinomas.

The so-called homebox (HOX) was described as a highly conserved DNA motif of 183 base pairs, encoding the 61 amino acid DNA-binding homeodomain. Numerous HOX genes have subsequently been shown to bind to DNA and regulate the transcription of other genes. In humans the class I HOX genes are placed in four clusters on different chromosomes. The order of the genes within each of these clusters is evolutionarily conserved to a high degree and suggests that such an organization may be essential in the function of these genes during normal embryo- and histogenesis. Re-expression of HOX gene products has been reported in a wide variety of neoplastically transformed cells and it seems very likely that the HOX genes represent yet another class of oncofetal antigens involved in both normal development and cellular carcinogenesis, as well as tumor progression. The expression pattern of three homeobox gene products (HOX-B3, HOX-B4, and HOX-C6), all shown to be involved in lung tissue development, was examined immunocytochemically, in human lung carcinoma (LC) tissues. In all observed LC cases, HOX-C6 was present in over 60% of neoplastic cells (+3) demonstrating a medium grade (B and C) staining intensity. A smaller number of neoplastically transformed epithelial cells also expressed the proteins HOX-B3 and -B4 (10% to 60% or +2 to +3 and a medium grade staining intensity or B and C). The significance of these novel oncofetal antigens in tumor cell biology and as target molecules in the immunotherapy of lung carcinomas should be established by future studies.