High-mobility group (
HMG) proteins are nonhistone
nuclear proteins that play an important role in the regulation of
chromatin structure and function. HMGI-C and HMGI(Y) are members of the HMGI family of
HMG proteins, and their expression in adult tissues generally correlates with malignant
tumor phenotypes. However, HMGI-C and HMGI(Y) dysregulation as a result of specific rearrangements involving 12q15 and 6p21, the respective chromosomal sites in which the HMGI-C and HMGI(Y) genes are located, is also identified in a variety of common benign mesenchymal
tumors, such as
lipomas and uterine leiomyomata. The general prevalence of HMGI-C and HMGI(Y)
protein expression and its correlation with chromosomal alterations in these benign
tumors are unknown. We analyzed 95 human
tumors (20
lipomas, 21 pulmonary chondroid
hamartomas, 26 uterine leiomyomata, and 28 endometrial
polyps) representing a selection of the benign lesions in which karyotypic alterations involving the chromosomal regions 12q15 and 6p21 are frequently detected. All cases were successfully karyotyped and some of them analyzed by fluorescent in situ hybridization with probes spanning the HMGI-C and HMGI(Y) genes. The results of this study demonstrate that expression of HMGI-C or HMGI(Y) is a common occurrence in
lipomas, pulmonary chondroid
hamartomas, leiomyomata, and endometrial
polyps; that it correlates with 12q15 and 6p21 chromosomal alterations (p < 0.001); and that it is compatible with rearrangement of the HMGI-C and HMGI(Y) genes. The expression pattern and cellular localization of the immunoreactivity support the view that in biphasic lesions composed of a mixture of both stromal and epithelial cells, such as pulmonary chondroid
hamartoma and endometrial
polyps, the mesenchymal component is the site of the HMGI genetic alterations.