Androgen receptor mRNA under-expression
in poorly differentiated human hepatocellular carcinoma
D. Tavian1, G. De Petro1, A. Pitozzi1, N. Portolani2, S.M.
Giulini2 and S. Barlati1
1Division of Biology and Genetics, Department of Biomedical
Sciences and Biotechnology, and 2First General Surgery, University
of Brescia, Brescia, Italy
Offprint requests to: Prof.
Sergio Barlati, Division of Biology and Genetics, Department of
Biomedical Sciences and Biotechnology, University of Brescia,
19 Valsabbina Street, 25123 Brescia, Italy. Fax: (39-030) (3701157.
e-mail: barlati@med.unibs.it
Summary. Many studies suggest that hepatocellular carcinoma
(HCC) is an androgen-dependent tumor with an incidence five times
higher in males, but few data are available on the androgen receptor
(AR) mRNA levels in different physiological classes of human liver
specimens.
In this study 108 human hepatic samples have been analyzed for
AR mRNA expression by a comparative RT-PCR assay. These consisted
of 35 non-tumoral hepatic samples (3 normal parenchymas, 4 steatosis,
10 hepatitis, 18 cirrhosis), 38 tumoral specimens derived from
uninodular and multinodular HCCs and 35 peritumoral hepatic tissues.
Normalized AR mRNA levels in tumoral and peritumoral liver tissues
spanned from 0 to 146% and from 7 to 125% respectively. Only in
a relatively small percentage of HCCs, the levels of expression
of AR mRNA were higher than in the corresponding peritumoral tissues
(16% of total HCCs). Although extremely variable, the AR mRNA
levels were related to histological tumoral differentiation and
proved to be lower in the highly dedifferentiated HCCs as compared
to the well differentiated ones.
Therefore, the evaluation of AR expression in HCC patients might
be relevant for the planning of clinical studies on anti-androgen
therapies, which might be useful only in the cases in which a
high level of AR mRNA is detected, considering the high heterogeneity
of AR mRNA levels which characterizes HCC samples. It is likely
that the HCCs, expressing low or undetectable levels of AR mRNA,
would not benefit by the anti-androgen therapy. Histol. Histopathol.
17, 1113-1119 (2002)
Key words: Hepatocellular carcinoma, Androgen receptor,
mRNA expression, Tumoral differentiation, Anti-androgen therapies
DOI: 10.14670/HH-17.1113