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Laboratory of Tumor Immunology and Biology, Division of Cancer Biology and Diagnosis and Centers, National Cancer Institute, NIH, Bethesda, Maryland 20892 [T. S., C-F. Q., N. N., N. K., D. S. S.]; Division of Cytokine Biology, Food and Drug Administration, Bethesda, Maryland 20892 [K. S., G. R. J.]; Molecular Oncology Laboratory, Imperial Cancer Research Fund, Hammersmith Hospital, London, England W12 0H8 [W. J. G.]; Department of Pathology, Hiroshima University Hospital, School of Medicine, 1.2.3. Kasumi, Minaiku, Hiroshima, Japan [E. T.]; and Cattedra di Oncologia Media, II Facolta' di Medicina e Chirurgia Universita' degli Studi di Napoli, 80131 Napoli, Italy [F. C.]
Thirty-six primary human colorectal tumors, 43 noninvolved colon samples that were adjacent to either carcinomas or adenomas, 22 adenomas, and nine normal colon specimens were immunohistochemically examined for the presence and localization of two epidermal growth factor-related peptides, amphiregulin (AR) and cripto. Within the primary tumors, 18 (50%) showed moderate levels of AR expression. Approximately 60% of the tubular and tubulovillous adenomas were positive for AR expression, whereas only 15% of the adjacent, noninvolved colon mucosa expressed AR. A greater proportion of well-differentiated tumors (71%) were positive for AR expression than were poorly differentiated tumors (18%). All of the nine normal colon specimens were positive. Consequently, AR expression appeared to be associated with both normal and malignant epithelial cells that were more differentiated. The distribution of cripto expression was different. Seventy-nine % of the colon tumors expressed cripto with a frequency of expression that was approximately equivalent between well-differentiated and poorly differentiated tumors. Approximately 86% of the tubulovillous adenomas, but only 43% of the tubular adenomas, were positive for cripto expression. In contrast, whereas AR was expressed in normal colon specimens, none of these tissues expressed cripto, and only 12% of the noninvolved normal colon samples adjacent to tumors or adenomas were positive for cripto. Cripto expression therefore appeared related to neoplasia. These data suggest that AR and cripto may be functioning as potential autocrine and/or paracrine growth factors in the colon and that the differential expression of cripto may serve as a potential tumor marker for colonic carcinogenesis.
1 To whom requests for reprints should be addressed.
Received 2/ 3/92. Accepted 4/ 1/92.
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