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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 |
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G. Tallini, R. Vanni, G. Manfioletti, B. Kazmierczak, G. Faa, P. Pauwels,
J. Bullerdiek, V. Giancotti, H. Van Den Berghe, P. Dal Cin
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Department
of Pathology (GT), Yale University School of Medicine, New Haven, Connecticut;
Dipartimento di Scienze Applicate ai Biosistemi (RV) and Dipartimento di
Citomorfologia (GF), University of Cagliari, Cagliari, Italy; Dipartimento
di Biochimica (GM, VG), Biofisica e Chimica delle Macromolecole, University
of Trieste, Trieste, Italy; Center for Human Genetics & Genetic
Counseling (BK, JB), University of Bremen, Bremen, Germany; Department of
Pathology (PP), Stichting PAMM, Eindhoven, The Netherlands; The Center for
Human Genetics (HVDB), University of Leuven, Leuven, Belgium; Department
of Pathology (PDC), Brigham and Women's Hospital, Boston, Massachusetts |
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SUMMARY: 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. (Lab Invest 2000, 80: 359-369)
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