Cell kinetics in colorectal carcinoma progression: proliferation or apoptosis?

Abstract

INTRODUTION: The growth and development of tumours depend on the balance between cell proliferation and cell death apoptosis. Since the adenoma - carcinoma sequence is well established in colorectal carcinogenesis it provides an ideal model for the study of this concept. OBJECTIVE: To evaluate the proliferation, apoptosis and the expression of the apoptotic gene P53 in normal (N), adenoma (A). early carcinoma (C) and late carcinoma (LC) and to determine any differences in the above groups.METHODS: 49 ECC arising in adenomas, belonging to Dukes A (pT1) were retrieved from the histopathology files of the Queens Medical Centre. Nottingham. Blocks containing discrete areas of N, A and EC were identified for immunohistochemical staining with MIB I, M30 and P53 to assess proliferation, apoptosis and P53 gene expression. The Proliferation index (Pl), apoptotic index (AI) and P53 labelling index (P53 LI) were derived by counting 500 cells from each of the above tissue regions and giving the number of cells expressing each antigen as a percentage. J 9 LC belonging to Dukes C (pT3 and pT4) were also assessed similarly. The one way analysis of variance (ANOVA) was used to compare the means of Pl, Al and P53Ll among N, A and EC groups and an unpaired T test to compare the EC and LC group . RESULTS: The PIs were (mean+ SD) 17.0 (6.6), 51.6 (12.7), 57.8 (13.2) and 63.5 (8.8) for the groups SN, A, EC and LC respectively (Annova, fvalue=l 87.72 sig P= 0.00 unpaid t test f value 6.078, P=O 16), The Als (mean and range) were 0. 7 (0.09), 1.9( 1.5), 3.1 (2.1) and 3.5 ( 1.9) were for the groups N, A, EC and LC respectively (Annova, fvalue 11.01 sig P 0.00, t test 0.004, P= 0.952). For the four groups ofN, A, EC and LC the P 53 Lis were (mean and SD) 0,6 ( 6.8), 48.9 (21.7), 47.6 (30.7 ), 59.8 (25,3) respectively (Annova. f value=52.55, sig= P0.00 and t test, fvalue 1.002, p== 0,321 ). CONCLUSIONS: The increase in Pl in the N, A, EC and LC group reached a level of statistical significance. The Al and P53LI though different among most groups was not of statistical significance in the A, EC and LC groups signifying that even following malignant transformation cell proliferation keeps increasing whilst a marked change in apoptosis per se is not seen in colorectal carcinoma progression.