| [Object] To demonstrate the regulation of proliferation, aoptosis and the significance of related regulatory factors in all stages of colon carcinogenesis and progression through detecting proliferation index, aoptosis index, proliferation and apoptosis ratio, the positive expression of P53, bcl-2 and COX-2.[Methods] 81 specimens resected surgically in 2000-2010 were collected from Department of Pathology, The First Affiliated Hospital of Kunming Medical College, which were reserved as paraffin blocks with completed clinical documents. All Specimens used for this study were composed of 15 normal colonic mucosa and18 colonic adenomas,15 colonic adenocarcinomas of Duke's A stage,18 colonic adenocarcinomas of Duke's B stage,15 colonic adenocarcinomas of Duke's C stage. Te positive expression of Ki-67, bcl-2, P53, COX-2 in all Specimens were detected by Immunohistochemistry and Ki-67 proliferation index (LI) were calculated. Apoptosis index (AI) were assesed by TUNEL [terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling] technique labeled apoptotic cells, and then the apoptotic/proliferation ratio (AI/PI) were calculated. All of the results were statisticed by using software SPSS 11.5.[Results] The expression of Ki-67 was localized in the nucleus. In normal colorectal mucosa, the expression of Ki-67 was mainly in the crypt bottom, and mostly were light yellow and yellow. In colonic adenoma and adenocarcinoma, the expression of Ki-67 was irregularly dispersed, mostly were yellow brown. The expression of bcl-2 was localized in the cytoplasm. In normal colorectal mucosa, the most expression of bcl-2 were negative and light yellow, mainly located in the mucosal surface. In colon adenoma and adeno carcinoma, the expression of bcl-2 were more irregularly distributed with yellow and light yellow. The expression of P53 was localized in the nucleus. There was almost no expression of P53 in normal colorectal mucosa. There were few specimens of colorectal adenomas with positive expression of P53. There were much more specimens of colorectal adenocarcinoma with positive expression of P53 and most of their nucleus were yellow and brown. The expression of COX-2 was localized in the cytoplasm. COX-2 was widely expressed in the cytoplasm in normal colon, colonic adenoma and adenocarcinoma. Most of specimens were yellow and brown. Apoptotic cells were round and stained brown, seperated from adjacent cells. Apoptotic cell cytoplasm and nuclear chromatin were condensed in the nuclear membrane, the nucleolus were cracking. In normal colonic mucosa, apoptotic cells were few and located in the mucosal surface, occasionally observed among the glands, few were observed at the bottom of crypt; in colorectal adenomas, the number of apoptotic cells increased significantly, less in mucosal surface and more in crypt bottom than normal colonic mucosa. It was showed more apoptotic cells in the villous component; in colon adenocarcinoma, apoptotic cells were scattered focally. The positive expression rate of ki-67 in normal colonic mucosa, colon adenomas, Dukes'A stage, Dukes'B stage, Dukes'C stage of colon adenocarcinoma were 31.0%,74.1%,59.5%,72.3%,68.1%. The differences between five groups were statistically significant (p<0.001). The positive expression rate of bcl-2 in normal colonic mucosa, colon adenomas, Dukes'A stage, Dukes'B stage, Dukes'C stage of colon adenocarcinoma were 13.3%,70.6%,63.6%,83.5%,80.5%. The differences between five groups were statistically significant (p<0.001). The positive expression rate of P53 in normal colonic mucosa, colon adenomas, Dukes'A stage, Dukes'B stage, Dukes'C stage of colon adenocarcinoma were 7.1%,61.1%,48.5%,79.6%,67.1%. The differences between five groups were statistically significant (p<0.001). The positive expression rate of COX-2 in normal colonic mucosa, colon adenomas, Dukes'A stage, Dukes'B stage, Dukes'C stage of colon adenocarcinoma were 85.83%, 76.4%,84.0%,82.1%,67.1%. The differences between five groups were not statistically significant (p>0.05). Apoptotic index in normal colonic mucosa, colon adenomas, Dukes'A stage, Dukes'B stage, Dukes'C stage of colon adenocarcinoma were 1.6%,6.7%,4.5%,3.7%,3.2%. The differences between five groups were statistically significant (p<0.001). AI/PI In normal colonic mucosa, colon adenomas, Dukes'A stage, Dukes'B stage, Dukes'C stage of colon adenocarcinoma were 0.04,0.08,0.05,0.04,0.04, the differences between five groups were statistically significant (p<0001). The correlation coefficient(rs) between AI/PI and the expression of bcl-2, P53 were -0.570,-0.490. Both of bcl-2 and P53 were correlated with AI/PI(P<0.001). While the expression of COX-2 was not correlated with AI/PI (P> 0.05).[Conclusion] 1. Cell proliferation and apoptosis have increased from normal colon mucosa to colon adenomas. In this stage, tumor tissue is in a state with growing strongly and the internal structure are being remoded; 2. Cell proliferation, apoptosis and apoptosis/proliferation ratio have decreased gradually from colom adenoma to adenocarcinoma. It is revealed that tumor cells have had a quantitative change in this stage and this change lead to clones with rapid growth be selected. Then tumor will be in a stage with the balance of proliferation and apoptosis; 3. The apoptosis/ proliferation ratio is in relative steady from adenocarcinoma without lymph node metastasis and adenocarcinoma with lymph node metastasis. However, apoptosis /proliferation ratio remais a high level state. It domanstrates the tumor cells with highly malignant charactors have been fomed to promote tumor invasion and metastasis; 4. The expression of bcl-2 and P53 are closely related to AI/PI in the process of colon neoplasm. They play a crucial role in bilateral regulating cell proliferation and apoptosis. Their high expression can promot tumor cell proliferation and inhibit apoptosis. The expression of COX-2 is not related with AI/ PI in n the process of colon neoplasm.
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