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(American Journal of Pathology. 2000;156:577-584.)
© 2000 American Society for Investigative Pathology

Regular Articles

Expression of a Novel Transmembrane Carbonic Anhydrase Isozyme XII in Normal Human Gut and Colorectal Tumors

Antti Kivelä^*, Seppo Parkkila^*, Juha Saarnio, Tuomo J. Karttunen^§, Jyrki Kivelä^*¶, Anna-Kaisa Parkkila^*, Abdul Waheed^||, William S. Sly^||, Jeffrey H. Grubb^||, Gul Shah^||, Özlem Türeci^** and Hannu Rajaniemi^*

From the Departments of Anatomy and Cell Biology,^*
Clinical Chemistry,
Surgery,
and Pathology,^§
University of Oulu, Oulu, Finland; the Parolannummi Garrison Hospital,^¶
Hattula, Finland; the Department of Biochemistry,^||
St. Louis University School of Medicine, St. Louis, Missouri; and the Department of Internal Medicine,^**
University of Saarland, Homburg, Germany

Carbonic anhydrase isozyme XII is a recently discovered member of the -carbonic anhydrase gene family with a suggested role in von Hippel-Lindau gene-mediated carcinogenesis. Increased expression of its mRNA has been observed in renal and lung carcinomas. This paper presents the localization of CA XII in the normal human gut and in colorectal tumors. Immunohistochemistry performed using a polyclonal antibody raised against truncated CA XII revealed prominent polarized staining for CA XII in the basolateral plasma membrane of the enterocytes of the normal large intestine, the reaction being most intense in the surface epithelial cuff region. Most colorectal tumors displayed abnormal expression of CA XII; the most dramatic change was observed in the deep parts of the adenomatous mucosa, where the positive immunoreaction clearly increased along with the grade of dysplasia. Adenomas with severe dysplasia and carcinomas showed an equal, diffuse staining pattern. The results indicate region-specific regulation of CA XII expression along the cranial-caudal axis of the human gut, whereas its diffuse expression in the most malignant tumors seems to correlate with their biological behavior.

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