The high-mobility-group (HMG) protein gene HMGI-C is apparently involved in the genesis of a variety of benign human solid tumors with rearrangements of chromosomal region 12q14-15 affecting the HMGI-C gene. So far, no expression of HMGI-C has been found in adult tissues, and no data are available on the expression of HMGI-C in primary human malignant tumors of epithelial origin. Therefore, we analysed the HMGI-C expression patterns in 44 breast cancer samples and 13 samples of nonmalignant adjacent tissue by hemi-nested reverse transcriptase-polymerase chain reaction for HMGI-C expression. There was no detectable expression of HMGI-C in any nonmalignant adjacent breast tissues analyzed. In contrast, we found expression in 20 of 44 breast cancer samples investigated. In invasive ductal tumors, expression was noted predominantly in tumors with high histologic grade: 17 of 21 breast cancer samples with histologic grade 3 but only three of 16 samples with histologic grades 1 or 2 showed expression of HMGI-C. In addition, all seven lobular breast cancer samples tested did not express HMGI-C. From these results, we concluded that HMGI-C expression may be of pathogenetic or prognostic importance in breast cancer.
The high mobility group gene, HMGA2, is frequently expressed in uterine leiomyomata (UL) with chromosomal rearrangements of 12q15. In contrast, HMGA2 expression has not been detected in karyotypically normal UL or in myometrium, but has been detected in these tissues after culture. To characterize further the expression pattern of HMGA2, we assessed HMGA2 expression by RT-PCR followed by Southern blot hybridization, and by real-time PCR in three tissue panels: (1) primary myometrial cultures, (2) uncultured tissue from 15 karyotypically normal samples consisting of eleven 46,XX UL and four matched myometrial specimens, and (3) uncultured tissue from ten UL with 12q15 rearrangements and three matched myometrial specimens. HMGA2 expression was detected in all samples from the three panels. The level of HMGA2 expression in karyotypically normal UL was similar to the level of expression in myometrium; however, it was significantly less than the level measured in UL with 12q15 rearrangements. This expression analysis by use of detection methods of different sensitivities underscores the importance of studies of HMGA2 expression in uncultured tissues and of careful interpretation of results from experiments on cultured cells. Moreover, detection of HMGA2 expression in myometrium and in UL without 12q15 rearrangements, tissues previously thought not to express HMGA2, suggests that HMGA2 expression is required in normal adult myometrial physiology.
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