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Distribution of Cells Expressing myc Proteins in Human Colorectal Epithelium, Polyps, and Malignant Tumors¹

Departments of Pathology [M. F. M.] and Medicine [A. I. M., G. G. F.], University of Pittsburgh School of Medicine, and Department of Biological Sciences, University of Pittsburgh [J. M. P.], Pittsburgh, Pennsylvania 15260; VA Medical Center, Pittsburgh, Pennsylvania 15240 [M. F. M., A. I. M., G. G. F.]; Cell Biology Department, Abbott Laboratories, North Chicago, Illinois 60064 [W. H. B., I. I. T.]; and Molecular and Cellular Biology Department, Amgen, Inc., Thousand Oaks, California 91320 [M. O. J., R. A. K.]

The myc gene family encodes nuclear phosphoproteins that are thought to play a role in the control of cellular proliferation and differentiation.

We have undertaken an immunohistochemical study assessing the expression of myc gene family proteins in individual cells of normal colonic mucosa, colorectal polyps, and colorectal adenocarcinomas. We screened a panel of mouse monoclonal antibodies that we raised against recombinant human c-myc and N-myc proteins for recognition of myc proteins in paraffin tissue sections. Two of these antibodies, H120C69 and H8C150, were selected for indirect immunoperoxidase staining of tissue sections from 16 normal mucosas, 24 polyps, and 30 adenocarcinomas. In normal colon, about 25% of the cells in the lower one-third of the crypts of Lieberkühn stain for myc-related protein. This distribution resembles that of proliferating cells in the crypt. Benign hyperplastic polyps resemble normal mucosa in their myc staining pattern, with about 25% of the cells positive. In adenomatous polyps, the putative precursors of adenocarcinomas, from 50 to 100% of the cells stain positively for myc protein. In these cases, stained cells extend to the luminal surface, consistent with the previously reported expansion of the proliferation zone in these lesions. All adenocarcinomas examined had increased levels of myc protein relative to normal mucosa. The tumor cells exhibited markedly heterogeneous myc staining patterns, both among different tumors and, in some cases, within a single tumor. Comparison with Ki-67 monoclonal antibody staining indicates that myc protein expression in many tumors is uncoupled from cellular proliferation. Surprisingly, we observed increased numbers of myc-expressing cells and increased levels of myc protein in histologically normal colon directly adjacent to tumor, suggesting that many colorectal carcinomas secrete growth factors that activate gene expression in neighboring normal mucosa.

¹ This work was supported by NIH Grant CA46547 (J. M. P.), by VA Merit Review Award S21 (A. I. M.), and by funds from the Pittsburgh Cancer Institute, Abbott Laboratories, and Amgen, Inc.

² To whom requests for reprints should be addressed, at Department of Pathology, University of Pittsburgh School of Medicine, VA Medical Center, University Dr. C, Pittsburgh, PA 15240.

Received 4/20/92. Accepted 8/18/92.

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