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Absence or Reduction of Fhit Expression in Most Clear Cell Renal Carcinomas¹

Department of Genetics and Pathology, Pomeranian Medical Academy, 70-111 Szczecin, Poland [P. H., J. L.]; Department of Pathology, Medical Academy, 71-252 Szczecin, Poland [M. M., W. D.]; Department of Microbiology and Immunology, Kimmel Cancer Institute [Z. S., T. D., Y. P., M. O., K. H.], and Department of Pathology, Anatomy and Cell Biology [P. A. M.], Jefferson Medical College, Philadelphia, Pennsylvania 19107

The FHIT gene at human chromosome region 3p14.2 straddles the common fragile site, FRA3B, and numerous homozygous deletions in cancer cell lines and primary tumors. Also, the 3p14.2 chromosome breakpoint of the familial clear cell kidney carcinoma-associated translocation, t(3;8)(p14.2;q24), disrupts one FHIT allele between exons 3 and 4, fulfilling one criterion for a familial tumor suppressor gene: that one allele is constitutionally inactivated. Because the FHIT gene sustains biallelic intragenic deletions rather than mutations, there has not been evidence that the FHIT gene frequently plays a role in kidney cancer, although replacement of Fhit expression in a Fhit-negative renal carcinoma cell line suppressed tumor growth in nude mice. We have now assessed 41 clear cell renal carcinomas for expression of Fhit by immunohistochemistry. Normal renal tubule epithelial cells express Fhit uniformly and strongly, whereas 51% of the tumors are completely negative, 34% of tumors show a mixture of positive and negative cells, and 14% are uniformly positive, although usually less strongly positive than the normal epithelial cells. Most interestingly, there was a correlation between complete absence of Fhit and the G1 morphological grade and early clinical stage. Morphological grades G2 and G3 exhibited a mixture of positive and negative cells with a tendency for a higher fraction of negative cells in G3. Fhit inactivation is likely to be an early event in G1 tumors and may be associated with progression in G2 and G3 tumors.

¹ This work was supported by the United States-Poland Maria Sklodowska-Curie Joint Fund II Grant MZ/NIH-96-287, by United States Public Health Service Grants CA21124 and CA56336 from the National Cancer Institute and a grant to P. H. from the Foundation for Polish Science.

² To whom requests for reprints should be addressed, at Department of Genetics and Pathology, Pomeranian Medical Academy, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland. Phone: 48 91 482-4741; Fax: 48 91 482-8450; E-mail: phadacze@pam.szczecin.pl.

³ Present address: Banyu Tsukuba Research Institute, Okubo 3, Tsukuba, 300-33 Japan.

Received 2/27/98. Accepted 5/29/98.

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