Y. Tamimi et al., INCREASED EXPRESSION OF HIGH-MOBILITY GROUP PROTEIN I(Y) IN HIGH-GRADE PROSTATIC-CANCER DETERMINED BY IN-SITU HYBRIDIZATION, Cancer research, 53(22), 1993, pp. 5512-5516
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.