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Down-Regulation of the KAI1 Metastasis Suppressor Gene during the Progression of Human Prostatic Cancer Infrequently Involves Gene Mutation or Allelic Loss¹

The Oncology Center [J-T. D., H. S., G. S. B., W. B. I., J. T. I.], Department of Urology and the James Buchanan Brady Urological Institute [S. S. P., G. S. B., W. B. I., J. T. I.], and Department of Pathology [G. S. B.], Johns Hopkins University School of Medicine, Baltimore, Maryland 21231; Urology Research Lab, Nijmegen University, Nijmegen, the Netherlands [J. A. S.]; and National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 [J. C. B.]

The KAI1 gene, located on human chromosome 11p11.2, suppresses tumor metastasis when expressed in certain cancer cells. To evaluate whether dysregulation of KAI1 occurs during the progression of human prostatic cancer, protein expression, mutation, and allelic loss of KAI1 were analyzed using a tissue bank of 98 primary cancers and 32 metastases. By immunohistochemical staining, high levels of KAI1 protein are detected in the epithelial but not stromal compartment of normal prostatic and benign prostatic hyperplasia tissue. In epithelial cells, KAI1 protein is expressed on the plasma membrane. KAI1 protein expression is down-regulated in more than 70% of the 49 primary prostatic cancers from untreated patients. In 10 such untreated patients, down-regulation of KAI1 protein occurred in all of the lymph node metastases examined. In 15 patients with metastatic disease who had failed androgen ablation therapy, more than 90% of the primary prostatic cancers had down-regulation, with 60% having no KAI1 protein expression. Primers derived from the sequences flanking each exon of KAI1 were used to analyze KAI1 mutation and allelic loss by the method of PCR-single-strand conformational polymorphism. Using this method, no point mutation or allelic loss was detected in metastases from 10 patients. No allelic loss was detected in an additional 34 primary and 12 lymph node metastases via microsatellite analysis using the marker D11S1344, which is located in the region of KAI1. These results demonstrate that KAI1 protein expression is consistently down-regulated during the progression of human prostatic cancer and that this down-regulation does not commonly involve either mutation or allelic loss of the KAI1 gene.

¹ Supported by Specialized Programs of Research Excellence Grant CA 58236 (National Cancer Institute).

² To whom requests for reprints should be addressed, at Johns Hopkins Oncology Center, 422 North Bond Street, Baltimore, MD 21231.

Received 7/25/96. Accepted 8/16/96.

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