INCREASED EXPRESSION OF HIGH-MOBILITY GROUP PROTEIN I(Y) IN HIGH-GRADE PROSTATIC-CANCER DETERMINED BY IN-SITU HYBRIDIZATION

In a previous study using the Dunning rat prostate cancer model, we fo und high mobility group protein I-(Y) [HMG-I(Y)] to be overexpressed i n metastatic tumor lines when compared to nonmetastatic lines. Hence, overexpression of this 12-kDa non-histone chromosomal protein may be a ssociated with tumor progression. Firstly, by Northern analysis we sho wed that HMG-I(Y) expression increases in high grade prostate tumors. These studies, however, required fresh material, and clinical follow-u p was limited. To overcome this problem paraffin-embedded material mus t be made amenable for determination of HMG-I(Y) expression in retrosp ective studies. RNA in situ hybridization enables the evaluation of mR NA levels in such material. We studied tumors from 71 patients with pr ostate cancer. The microscopic analysis of each sample included: (a) h ybridization on sections with sense HMG-I(Y) and (b) 28S rRNA probes ( nonspecific signal); (c) hybridization with antisense 28S rRNA (RNA pr eservation); (d) hybridization with an antisense HMG-I(Y) probe [quant ification of HMG-I(Y) mRNA in the expressing areas]. Data were quantif ied using an image analysis system. High expression of HMG-I(Y) was ob served in regions with high Gleason grade (4 and 5); whereas in lesion s of Gleason grade 3, both weak and no expression was observed. In are as of grade 1 and 2, as well as in normal glands, low or no expression was found. We conclude that HMG-I(Y) expression assessed by RNA in si tu hybridization is related to tumor differentiation in prostate cance r. These findings indicate that HMG-I(Y) expression may be a marker in prostate cancer diagnosis, and the possible clinical implication of e xpression of this gene in malignancy is discussed in this report.