HMGI-C and HMGI(Y) immunoreactivity correlates with cytogenetic abnormalities in lipomas, pulmonary chondroid hamartomas, endometrial polyps, and uterine leiomyomas and is compatible with rearrangement of the HMGI-C and HMGI(Y) genes

High-mobility group (HMG) proteins are nonhistone nuclear proteins that pla y 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 thei r expression in adult tissues generally correlates with malignant tumor phe notypes. However, HMGI-C and HMGI(Y) dysregulation as a result of specific rearrangements involving 12q15 and 6p21, the respective chromosomal sites i n which the HMGI-C and HMGI(Y) genes are located, is also identified in a v ariety of common benign mesenchymal tumors, such as lipomas and uterine lei omyomata. The general prevalence of HMGI-C and HMGI(Y) protein expression a nd its correlation with chromosomal alterations in these benign tumors are unknown. We analyzed 95 human tumors (20 lipomas, 21 pulmonary chondroid ha martomas, 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 w ere successfully karyotyped and some of them analyzed by fluorescent in sit u hybridization with probes spanning the HMGI-C and HMGI(Y) genes. The resu lts of this study demonstrate that expression of HMGI-C or HMGI(Y) is a com mon occurrence in lipomas, pulmonary chondroid hamartomas, leiomyomata, and endometrial polyps; that it correlates with 12q15 and 6p21 chromosomal alt erations (p < 0.001); and that it is compatible with rearrangement of the H MGI-C and HMGI(Y) genes. The expression pattern and cellular localization o f the immunoreactivity support the view that in biphasic lesions composed o f a mixture of both stromal and epithelial cells, such as pulmonary chondro id hamartoma and endometrial polyps, the mesenchymal component is the site of the HMGI genetic alterations.