Detection of human androgen receptor mRNA in hepatocellular carcinoma by in situ hybridisation

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Abstract
Recent evidence suggests that anti‐androgen therapy may be useful in patients with androgen receptor (AR)‐positive hepatocellular carcinomas (HCC), as determined by a steroid binding assay. To evaluate the AR expression of HCC, in both histological and cytological material, we developed a non‐radioisotopic in situ hybridisation (NISH) assay specific for the human AR mRNA. A synthetic oligonucleotide complementary to positions 661–695 of the human AR coding sequence was end‐labelled with digoxigenin‐dUTP and revealed by an alkaline phosphatase‐conjugated anti‐digoxigenin antibody. We analysed 22 formalin‐fixed, paraffin‐embedded HCC, obtained at surgery, together with the corresponding non‐neoplastic liver tissues (19 cases). In six cases, cell blocks obtained by fine‐needle aspiration (FNA) prior to surgery were also available. Positive controls included seminal vesicles and prostate tissues. Sixteen HCCs (73%) expressed a variable amount of AR mRNA, with the proportion of positive cells ranging from very few to more than 90%. Normal hepatocytes were stained weakly and focally in eight cases (42%). Appropriate controls, inclusive of immunohistochemical detection of the AR protein in selected cases, established the specificity of the assay. Data obtained on FNA specimens were predictive of the results on histologic material. However, in two cases the NISH assay was negative on the cytological specimen but stained rare hepatocytes within the surgically resected tumor. In conclusion, NISH is a novel procedure for rapid and specific assessment of the expression of AR in HCC tissue. Its clinical significance, in terms of predictivity of response to anti‐androgen treatment, needs to be assessed in large correlative studies.