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Pattern of Epithelial Cell Proliferation in Colorectal Mucosa of Normal Subjects and of Patients with Adenomatous Polyps or Cancer of the Large Bowel¹

The Colorectal Cancer Study Group of the University of Modena and the Health Care District 16. Istituto di Patologia Medica [M. P., L. R., P. D. D., L. T., O. S., M. G. A.], Istituto di Radiologia [G. M., D. D. M.], Cattedra di Gastroenterologia ed Endoscopia Digestiva [A. A., N. J. C., M. P., G. R.], Istituto di Clinica Chirurgica e divisione di Chirurgia d'Urgenza [G. B., A. M.], Università di Modena; Istituto di Clinica medica I [G. B., L. B.], Università di Bologna, Italy

Microautoradiography has been largely used to characterize the proliferative activity of colorectal mucosa. We used this technique in a large series of patients with polyps or cancer of the large bowel and in normal controls with the following objectives: (a) to define the normal pattern of cell replication in different tracts of the large bowel; (b) to compare the proliferative activity of colonic crypts in patients with colorectal cancer or polyps with that of controls; (c) to evluate replicative activity of colorectal mucosa in the close vicinity and at distance from a neoplastic mass. Specimens of colorectal mucosa were taken during endoscopy (controls and polyps) or at surgery (cancer). During histological examination each intestinal hemicrypt was divided into five equal longitudinal compartments from the base to the surface and the labeled cells in each compartment were counted. In controls, total labeling index (ratio of labeled to total cells) and labeling index per crypt compartment showed only minor differences between the various large bowel tracts. Total labeling index tended to be higher in patients with polyps or cancer than in controls (13.5 ± 0.4 and 12.5 ± 0.4, respectively, versus 11.3 ± 0.5). Labeling index per crypt compartment in the most superficial portions of the crypt (compartments 3 to 5) was significantly higher in the two groups of patients with tumors than in controls. This was particularly evident in the fifth compartment (the most superficial), in which labeled cells were observed in 15.8% (three subjects out of 19) of controls but in 71% (15 out of 21) and 87.5% (14 out of 16) of polyp and cancer patients, respectively. In patients with colorectal cancer there were not significant differences of cell proliferation between mucosal samples taken at various distances from the tumor margin; however, increased cell replication, especially in the most superficial portions of the crypt, has been observed. In conclusion, a significant upwards expansion of the proliferative zone of intestinal glands has been observed in patients with either polyps or cancer of the large bowel. In particular, labeling of the fifth compartment seems to possess the highest discriminatory power between subjects with or without intestinal neoplasms. Hyperproliferation of the entire colonic mucosa seems to be a common feature in patients with colorectal cancer.

¹ Parts of this work have been presented at the Fourth Italian Digestive Disease Week (Verona, June 6–8, 1986) and at the Autumn Meeting of the British Society of Gastroenterology (Cardiff, September 24–26, 1986). This work has been supported by Grant (60%) 1984–85 of the Ministero della Pubblica Istruzione, by Grant 85.0212.844 of the Consiglio Nazionale delle Ricerche (Progetto Finalizzato Oncologia), by a grant of the Regione Emilia-Romagna, delibera n. 1970, 13/5/1986, and by a grant of the Associazione Italiana Ricerca sul Cancro.

² To whom requests for reprints should be addressed, at Istituto di Patologia Medica Policlinico, Via del Pozzo, 71 41100-Modena, Italy

³ Supported by the Lega Italiana per la lotta contro i Tumori.

Received 11/ 3/87. Revised 2/24/88. Accepted 3/30/88.

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