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(American Journal of Pathology. 1999;154:1665-1671.)
© 1999 American Society for Investigative Pathology

Technical Advance

Frequent Loss of KAI1 Expression in Squamous and Lymphoid Neoplasms

An Immunohistochemical Study of Archival Tissues

Joseph Geradts*, Robert Maynard{dagger}, Michael J. Birrer{ddagger}, Denver Hendricks{ddagger}, Susan L. Abbondanzo§, Kwun M. Fong, J. Carl Barrett|| and Donald P. Lombardi**

From the Nuffield Department of Pathology and Bacteriology,*
University of Oxford, Oxford, England; Department of Hospital Laboratories,{dagger}
University of North Carolina Hospitals, Chapel Hill, North Carolina; the Biomarkers and Prevention Research Branch,{ddagger}
National Cancer Institute, Rockville, Maryland; the Department of Hematologic and Lymphatic Pathology,§
Armed Forces Institute of Pathology, Washington, DC; the Department of Thoracic Medicine,
The Prince Charles Hospital, Queensland, Australia; the National Institute of Environmental Health Sciences,||
Research Triangle Park, North Carolina, and the Department of Medicine,**
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

The metastasis suppressor gene KAI1 was identified by its ability to inhibit the formation of pulmonary metastases in experimental models for prostatic carcinoma. Down-regulation of this gene may be correlated with the invasive phenotype in melanomas and colon and bladder carcinomas and with the metastatic phenotype in carcinomas of the lung, breast, prostate, and pancreas. The goal of our study was to establish an immunohistochemical method to detect KAI1 expression in archival tissues. Using cell lines with known KAI1 levels and paraffin-embedded KAI1 positive tissues as controls, we observed strong membrane staining in lymphoid follicular centers and squamous epithelia. We then demonstrated the utility of our assay by studying KAI1 expression in 34 lymphoid and 57 squamous lesions. All eight reactive lymph nodes were KAI1 positive. In contrast, three of 13 follicular small cleaved and five of 13 diffuse large cell lymphomas were KAI1 negative. Seventy-nine percent (37 of 47) of invasive squamous cell carcinomas from the lung (n = 15), head and neck (n = 18), and cervix (n = 14) showed extensive KAI1 down-regulation. Loss of KAI1 expression was also found in a subset of 10 high-grade cervical dysplasias. Our data show that (i) immunohistochemistry is a suitable technique for evaluating KAI1 expression in archival tissues; (ii) KAI1 was not expressed in a subset of both low-grade and high-grade lymphomas; and (iii) there was extensive down-regulation of KAI1 in squamous cell carcinomas, suggestive of an important role of the gene in the suppression of invasion in these malignancies.




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