Expression of AbdB-type homeobox genes in human tumors.

BACKGROUND

Homeobox (HOX) genes of the ANT-C/BX-C type control rostral-caudal patterning during embryogenesis. Previous work has shown that tissues express unique HOX gene expression profiles that persist upon transplantation to distant sites. These properties suggest that analysis of HOX genes may be useful for the diagnosis and evaluation of primary and metastatic tumors.

EXPERIMENTAL DESIGN

We analyzed normal and neoplastic tissues for the expression of three AbdB-type HOX genes; HOXD10, HOXA9, and HOXC9 to evaluate three hypotheses: (a) that tumors express HOX genes found in their tissue of origin, (b) that metastatic tumors continue to express HOX genes found in the primary tumor, and (c) that the level of HOX expression is related to tumor grade.

RESULTS

Malignant tumors gave consistent patterns of HOX gene expression that paralleled their tissues of origin. Normal kidney and Wilm's tumors expressed all three genes. Other renal tumors expressed distinct permutations of the three genes. One epithelial Wilm's tumor expressed only an aberrant 0.3 kb HOXD10 transcript. Outside of the kidney, HOXD10 was most characteristic of uterine tumors, HOXA9 of colonic adenocarcinomas, and HOXC9 of two groups of tumors: neoplasms derived from neural crest and mesenchymal tumors derived from intermediate mesoderm. Metastatic tumors retained their HOX gene expression profiles and did not express HOX genes transcribed at the site of metastasis. While modulation of HOX gene expression was observed in some poorly differentiated tumors this was not a consistent measure of tumor grade.

CONCLUSIONS

HOX gene profile was a reliable indicator of histologic subtype in a variety of tumors and in selected cases provided useful diagnostic information. Persistent expression in metastatic tumors confirmed that HOX expression profiles are potentially useful for diagnosing tumors of unknown origin. Continued analysis of the relationship between level of expression and tumor grade/behavior is indicated.