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Cell Kinetic Evaluation of Human Colonic Aberrant Crypts¹

Istituti di Patologia Medica [L. R., M. P., M. P. d. L.] e Anatomia Patologica [R. F., C. D. G.], Università di Modena, Modena, Italy

Foci of aberrant crypts (ACF) have been observed on the unsectioned, methylene blue-stained mucosal surface of the human colon. Experimental evidence and the histological features of the lesions suggest that they might be early events in colon cancer development. The main objective of the present study was to evaluate cell kinetic properties of ACF in the human colon. Five samples of colon mucosa were collected immediately after operation following the administration of 500 mg of 5'-bromo-2'-deoxyuridine prior to surgery. ACF were then identified on the fixed, unsectioned, methylene blue-stained mucosal surface under a light microscope. Some specimens containing ACF were serially sectioned perpendicular to the luminal surface of the intestine, along with specimens of normal-appearing mucosa. Several sections were prepared for the immunohistochemical identification of 5'-bromo-2'-deoxyuridine-incorporating cells (in the S phase of the cell cycle). The results of this study demonstrated that aberrant crypts have more cells per crypt than normal glands. Total labeling index and labeling index values in each of the five longitudinal compartments in which each crypt was divided showed an increased total proliferative activity in all ACF examined, although limited to the lower crypt compartments in almost all aberrant crypts evaluated. These findings are in keeping with previous cell kinetic studies and observations in experimental animals and provide evidence of the involvement of human aberrant crypts in the stepwise process leading from normal mucosa to colon cancer.

¹ Parts of this work were presented at the 18th Meeting of the European Study Group for Cell Proliferation, Budapest, May 6–9, 1992; at the Annual Meeting of the American Gastroenterological Association, San Francisco, May 10–13, 1992; and at the 83rd Annual Meeting of the American Association for Cancer Research, San Diego, May 20–23, 1992. This work was supported by grants of the Region Emilia-Romagna (1970, 13/05/1986) and of the Italian Association for Cancer Research.

² To whom requests for reprints should be addressed, at Istituto di Patologia Medica, Policlinico, via Del Pozzo 71, 41100 Modena, Italy.

³ M. P. was supported by the Lega Italiana per la Lotta contro i Tumori.

(Colorectal Cancer Study Group of the University of Modena and the Health Care District 16, Modena, Italy)

Received 2/17/93. Accepted 5/10/93.

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