Expression of cyclin E and cyclin-dependent kinase 2 correlates with metastasis and prognosis in colorectal carcinoma.
The expression of cyclin E and cyclin-dependent kinases 2 (CDK2) in metastatic foci, the relationship of their expression with some clinicopathologic characteristics, and the correlation of their expression with prognosis remain unclear. To examine the roles of their expression in the progression of colorectal carcinoma, 21 normal mucosa, 9 hyperplastic polyps, 58 adenomas, 17 adenocarcinoma in adenomas, 203 primary cancers, 21 lymph node metastases, and 10 hepatic metastases were immunohistochemically stained with anti-cyclin E, anti-CDK2, and anti-Ki67 antibodies. In the carcinogenic process, both cyclin E and CDK2 expressions increased significantly. From the primary to the lymph node-metastatic foci, cyclin E protein remained unchanged, but CDK2 increased significantly. From the primary to the liver-metastatic foci, cyclin E apparently decreased, and CDK2 was reduced almost to zero. In primary carcinomas, the reduction of cyclin E was significantly associated with large tumor size, mucinous type, venous invasion, deep infiltration, lymph nodal metastasis, peritoneal metastasis, advanced stage, and poor prognosis. Decreased CDK2 was obviously correlated with large tumor size, venous invasion, deep infiltration, hepatic metastasis, advanced stage, and poor prognosis. Increased cyclin E protein was related to elevated CDK2, which was further linked to higher Ki67. Thus, CDK2 overexpression could facilitate lymph node metastasis. The overexpression of cyclin E and CDK2 may mainly promote the progression of early cancer. Anti-cyclin E or anti-CDK2 chemotherapy should be targeted to the cancers with such overexpression.
Li
J Q
JQ
First Department of Pathology, Kagawa Medical University, Kagawa, Japan.
Miki
H
H
Ohmori
M
M
Wu
F
F
Funamoto
Y
Y
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D042846:CDC2-CDC28 Kinases; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D019927:Cyclin E / Q000276:immunology / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000276:immunology / Q000378:metabolism*; D018572:Disease-Free Survival; D006801:Humans; D006965:Hyperplasia; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007417:Intestinal Polyps / Q000378:metabolism / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism*; D015996:Survival Rate
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D019927:Cyclin E; D019394:Ki-67 Antigen; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases