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Inducible Nitric Oxide Synthase (iNOS) Is Expressed Similarly in Multiple Aberrant Crypt Foci and Colorectal Tumors from the Same Patients¹

Department of Pathology [X. P. H., T. G. P., T. P. P.] and Department of Epidemiology and Biostatistics [J. S. R.], Case Western Reserve University School of Medicine and Cancer Center, Cleveland, Ohio 44106

Aberrant crypt foci (ACF) are the earliest identified neoplastic lesions in the colon. Aberrant expression of inducible nitric oxide synthase (iNOS or NOS2) has been documented in colorectal tumors, but expression of iNOS has not been reported in human ACF or multiple neoplastic lesions from the same patient. Immunohistochemical expression of iNOS was evaluated in 42 ACF, 14 adenomas, and 25 carcinomas and their adjacent normal mucosa. iNOS was strongly expressed in the normal colonic epithelial cells of all patients; it was markedly reduced in 21 of 42 (50%) ACF and in 14 of 25 (56%) carcinomas. The expression of iNOS was remarkably similar in multiple lesions from the same patient (P < 0.0001). These results suggest that the reduced expression of iNOS is a very early event in the development of some human colorectal tumors, and that host factors control the expression of iNOS similarly in premalignant and malignant colonic epithelial cells.

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