Proliferation rate of colonic mucosa in normal subjects and patients with colonic neoplasms: a refined immunohistochemical method.

Abstract

An increased colonic epithelial proliferation rate and an increase of the cryptal proliferative zone are probable markers of increased susceptibility to colonic cancer. In this study an immunohistochemical method using 5-bromodeoxyuridine (BrdUrd) In this study we describe our methodology to measure the proliferation rate of colonic mucosa in vitro using immunohistochemistry in normal controls and patients with colonic neoplasms. This study was performed using normal looking colonic mucosa, which is especially important in view of the potential use of this method for identification of high risk patients and in dietary intervention studies. MethodsBiopsy specimens of endoscopically normal looking colonic mucosa were taken at 30 cm from 10 healthy subjects (six men, four women, mean age 44-5 years, range 17 to 75 years) who underwent diagnostic sigmoidoscopy and who were found not to have organic colonic disorders. In all these patients a barium enema and histological examination of the biopsy specimens yielded normal results. Biopsy specimens of endoscopically normal looking colonic mucosa were taken at 30 cm from 14 patients (nine men, five women, mean age 68-7 years, range 47 to 85 years) who had one or more adenomatous colonic polyps or a colon carcinoma, or who had undergone surgery for colon carcinoma in the recent past. The polyps were located in the sigmoid colon and the tumours were localised throughout the whole colon and in the sigmoid. The size of the polyps ranged from 3 to 45 mm.

Influence of a Highly Purified Senna Extract on Colonic Epithelium

“…Biopsies were incubated with 5-bromo-2′-deoxyuridine (BrdU, Serva, Heidelberg, Germany) and proliferative activity was determined using immunohistochemical detection of BrdU-incorporation in S-phase cells as described previously [21]. Epithelial cell proliferation was expressed as labelling index (LI), which was defined as the percentage of labelled nuclei of the total number of nuclei in whole length cut colonic crypts.…”

“…The length of colonic crypts was determined by counting the number of cells per crypt column. A mean number of 15 crypts per patient were counted, which is well above the 12 crypts that are necessary to obtain a constant average value for proliferative activity [21]. The technician scoring the LI was blinded for the mode of bowel preparation.…”

Effect of tumor removal on mucosal protein synthesis in patients with colorectal cancer

“…Thus some authors reported an increased percentage of cells in the S-or M-phase in seemingly normal mucosa of patients with sporadic colorectal cancer when 5-bromodeoxyuridine or [ 3 H]thymidine incorporation was determined (2,16,18,23,26) or when mitoses were counted (20). On the other hand, using the same or similar (PCNA staining) histochemical methods, other investigators were unable to demonstrate such significant differences between mucosa from patients with colorectal cancer and that from healthy subjects (4,15,27).…”

“…At stage II, the maximum of the proliferative compartment shifts to the upper portion of the crypt, and, at stage III, the total number of replicating cells in the crypt rises, leading to mucosal hyperproliferation and subsequently, because of the influence of cofactors, to neoplastic transformations (adenoma). However, in patients with sporadic colorectal cancer, findings are controversial, and the scientific literature is divided into reports supporting (2,18,20,23,26) or contesting (1,4,15,21,22,27) the importance of the stage III defect for adenoma and carcinoma formation.…”

Calcium Supplementation as Prophylaxis against Colon Cancer?

“…In addition to stimulating outgrowth of (pre)malignant cells into tumors, hyperproliferation can also make cells more susceptible to adverse mutations. Colonic epithelial cell proliferation has been found by many investigators to be increased in subjects with an increased risk of colon can cer [7][8][9][10] and is thought to be an important factor in the development of colorectal neo plasms. This hyperproliferative state may be due to a genetic defect, as it is thought to be the case in familial adenomatous polyposis, or it may be induced by exogenous factors, i.e.…”