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KAI1 Expression Is Up-Regulated in Early Pancreatic Cancer and Decreased in the Presence of Metastases¹

Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Bern, Switzerland [X. G., H. F., H. U. G., M. Ka., M. W. B.]; Institute of Pathology, University of Bern, Switzerland [A. Z.]; and Division of Endocrinology, Diabetes, and Metabolism, Departments of Medicine, Biological Chemistry, and Pharmacology, University of California, Irvine, California 92717 [M. Ko.]

KAI1 is a metastasis suppressor gene for prostate cancer that is located on chromosome 11p11.2-13. Using Northern blot analysis and in situ hybridization, we studied expression of KAI1 mRNA in specimens from 14 normal pancreases and 27 primary pancreatic cancers, and then correlated the findings with the clinical and histopathological parameters of the patients. Northern blot analysis showed increased steady-state levels of KAI1 mRNA expression in 24 of 27 (89%) pancreatic cancer samples. In situ hybridization showed enhanced KAI1 mRNA levels in the pancreatic cancer cells in 82% cancer tissues. The stroma surrounding the cancer mass and normal pancreatic tissue adjacent to the cancer cells exhibited very low levels of KAI1 mRNA expression. Correlation of the mRNA levels obtained by Northern blot analysis with clinical parameters of the patients revealed that KAI1 mRNA levels were significantly higher (P < 0.01) in earlier tumor stages (I, II), compared with advanced tumor stages (III, IV) in which lymph node or distant metastases were present. Furthermore, poorly differentiated tumors had significantly higher KAI1 mRNA levels than those that were moderately or well differentiated (P < 0.05). No association between KAI1 expression and survival was found. Our results indicate that KAI1 mRNA expression is reduced in patients with advanced tumor stages. This suggests that reduction of KAI1 expression might enable pancreatic cancer cells to spread in lymph nodes and to distant organs.

¹ This work was supported by the Swiss National Fund's Grant SNF 32-39529 (to H. F.) and by Public Health Service Grant CA-40162 awarded by the National Cancer Institute (to M. Ko.).

² To whom requests for reprints should be addressed, at Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, CH-3010 Bern, Switzerland. Phone: 41 31 632 2404; Fax: 41 31 632 9732.

Received 7/31/96. Accepted 9/17/96.

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