Paradoxical correlations of cyclin-dependent kinase inhibitors p21waf1/cip1 and p27kip1 in metastatic colorectal carcinoma
| Autor: | J D, Cheng, B A, Werness, J S, Babb, N J, Meropol |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Cyclin-Dependent Kinase Inhibitor p21 Male Antineoplastic Agents Cell Cycle Proteins Adenocarcinoma Cyclins Image Processing Computer-Assisted Humans Life Tables Neoplasm Metastasis Aged Neoplasm Staging Aged 80 and over Tumor Suppressor Proteins Cell Cycle Cell Differentiation Middle Aged Adenocarcinoma Mucinous Survival Analysis Neoplasm Proteins Ki-67 Antigen Treatment Outcome Female Colorectal Neoplasms Microtubule-Associated Proteins Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 5(5) |
| ISSN: | 1078-0432 |
| Popis: | The cyclin-dependent kinase inhibitors (CDIs) p27kip1 and p21waf1/cip1 are key cell cycle-negative regulatory enzymes. The objective of this study was to correlate expression of p27kip1 and p21waf1/cip1 with survival, chemotherapy responsiveness, and expression of the proliferation marker Ki-67 in patients with advanced colorectal cancer. Immunohistochemistry was performed with antibodies to p27kip1, p21waf1/cip1, and Ki-67 on samples from 66 patients with metastatic colorectal carcinoma. Interpretation was performed by visual inspection and automated image analysis. Patients who obtained a response to chemotherapy had greater p21waf1/cip1 tumor staining with a mean of 10.0 positive cells/high-powered field, compared with 4.5 positive cells/high-powered field for nonresponders (P = 0.03). A positive Spearman correlation was seen between Ki-67 and p27kip1 (r = 0.48; P = 0.0001), as well as between Ki-67 and p21waf1/cip1 (r = 0.48; P = 0.0001). A trend toward shorter survival was seen in patients with positive specimens (median survival of 10 months for patients with both p27kip1- and p21waf1/cip1-positive specimens, compared with 22 months for patients with neither p27kip1- nor p21waf1/cip1-positive specimens). In contrast to that previously reported in normal colonic mucosa or early-stage colorectal cancer, we observed positive correlations of Ki-67 with both p27kip1 and p21waf1/cip1, a trend toward greater CDI staining indicating worse prognosis, and greater p21waf1/cip1 staining in tumors that were chemosensitive. These findings suggest that in the metastatic setting, CDIs may show altered function, compared with their role in the normal cell cycle. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|