BACKGROUND: Homeobox (HOX) genes of the ANT-C/BX-C type control rostra
l-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 analy
sis of HOX genes may be useful for the diagnosis and evaluation of pri
mary and metastatic tumors. EXPERIMENTAL DESIGN: We analyzed normal an
d 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 metastati
c tumors continue to express HOX genes found in the primary tumor, and
(c) that the level of HOX expression is related to tumor grade. RESUL
TS: Malignant tumors gave consistent patterns of HOX gene expression t
hat paralleled their tissues of origin. Normal kidney and Wilm's tumor
s expressed all three genes. Other renal tumors expressed distinct per
mutations of the three genes. One epithelial Wilm's tumor expressed on
ly an aberrant 0.3 kb HOXD10 transcript. Outside of the kidney, HOXD 1
0 was most characteristic of uterine tumors, HOXA9 of colonic adenocar
cinomas, and HOXC9 of two groups of tumors: neoplasms derived from neu
ral crest and mesenchymal tumors derived from intermediate mesoderm. M
etastatic tumors retained their HOX gene expression profiles and did n
ot express HOX genes transcribed at the site of metastasis. While modu
lation of HOX gene expression was observed in some poorly differentiat
ed tumors this was not a consistent measure of tumor grade. CONCLUSION
S: HOX gene profile was a reliable indicator of histologic subtype in
a variety of tumors and in selected cases provided useful diagnostic i
nformation. Persistent expression in metastatic tumors confirmed that
HOX expression profiles are potentially useful for diagnosing tumors o
f unknown origin. Continued analysis of the relationship between level
of expression and tumor grade/behavior is indicated.