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Variant Estrogen Receptor Messenger RNA Species Detected in Human Primary Hepatocellular Carcinoma¹

Chair of Gastroenterology [E. V., L. C., A. D., F. Z., A. G., A. M., P. B., F. M.] and Institute of Morbid Anatomy [L. L.], University of Modena, Via del Pozzo 71, 41100 Modena, Italy

The development of hepatocellular carcinoma (HCC) in addition to cirrhosis affects males in a significantly higher proportion than females. Liver estrogen receptors increase when HCC develops in males; however, these tumors usually respond poorly to antiestrogens. We have, therefore, hypothesized that, similar to breast cancer, estrogen receptors in males with HCC may be mutated.

Variant estrogen receptor transcripts (lacking exon 5 of the hormone binding domain) were investigated by reverse transcription-PCR in 14 patients (7 males and 7 females) with HCC. While females mostly displayed the wild-type transcript (both in peritumoral and in tumor liver tissue), males showed both transcripts in the cirrhotic tissue and almost only the variant in the tumor. As the variant ER transcripts when translated could give rise to truncated receptors still able to constitutively activate transcription, they may be key factors in favoring deregulated proliferation in the male liver.

¹ This work was supported by Grant 60% from the University of Modena and was presented, in part, at the American Association for the Study of the Liver meeting held in Chicago, 1994.

² To whom requests for reprints should be addressed, at Chair of Gastroenterology, University of Modena, Via del Pozzo 71, 41100 Modena, Italy.

Received 11/14/94. Accepted 12/16/94.

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