No abstract available.
Cyclins*

No abstract available.
Cyclins* ; Hematologic Neoplasms* ; Phosphotransferases*

BACKGROUND/AIMS: Gastric carcinoma is a major cause of morbidity and mortality in Korea. It evolves through dysplasia to an invasive adenocarcinoma. The carcinogenesis of dysplasia and adenocarcinoma in the stomach was investigated by examining the levels of mutant p53 protein, p21(waf1/cip1), and cyclin D1 expression in gastric dysplasia and invasive adenocarcinoma. METHODS: Formalin- fixed paraffin-embedded tumors were examined immunohistochemically using the monoclonal antibodies to the 53 protein, p21(waf1/cip1) and cyclin D1. RESULTS: Mutant p53 protein, p21(waf1/cip1) and cyclin D1 expression were found in 66.6% (12/18), 72.2% (13/18) and 33.8% (6/18) of dysplasia, and 45.0% (9/20), 15.0% (3/20) and 30.0% (6/20) of invasive adenocarcinoma, respectively. CONCLUSIONS: These results suggest that p21(waf1/cip1), which is controlled by the p53 protein, plays a more important role in the carcinogenesis of the stomach than cyclin D1.
Adenocarcinoma* ; Antibodies, Monoclonal ; Carcinogenesis ; Cyclin D1* ; Cyclins* ; Korea ; Mortality ; Stomach*

BACKGROUND: Aberrations of cell cycle-related genes have been reported to contribute to the formation and development of various human tumors. To investigate the gastric carcinogenesis, the expression of cell cycle-related genes (p53, p21wafl/cipl, cyclin D1 and Rb protein) compared to the morphological changes of gastric epithelial lesions were studied. METHODS: The expression of p53, p21wafl/cipl, cyclin D1 and Rb protein was immunohistochemically studied in a series of surgical specimens including the 36 normal/regenerating lesions and the 127 gastric epithelial proliferative lesions (GEPLs). The gastric epithelial proliferative lesions consisted of 25 regenerating epithelia with atypias (REAs), 27 low grade gastric dysplasias (LGDs), 17 high grade dysplasias (HGDs), 24 early gastrc carcinomas (EGCs), and 34 advanced gastric carcinomas (AGCs). RESULTS:The frequency of p53 protein overexpression was significantly associated with histologic grades of GEPLs (p=0.031); occurring in 4% of REAs, in 14.8% of LGDs, in 23.5% of HGDs, in 41.7% of EGCs and 58.9% of AGCs. The p21 wafl/cipl immunohistochemical reaction showed superficial eccentric positivity, representing an inverse correlation with histologic grades of GEPLs (p=0.04); occurring in 83.4% of normal/regenerating lesions, in 80% of REAs, in 74.1% of LGDs, in 29.4% of HGDs, 20.8% of EGCs and 8.8% of AGCs. Although Cyclin D1 and Rb proteins were expressed highly in the GEPLs, the frequency of both proteins were insignificantly associated with histologic grades of GEPLs (p=0.092). However, cases with both the Rb and cyclin D1 positivity were increased with statistical significance along histologic grades of GEPLs (p=0.044). CONCLUSIONS: The altered expression of p53, p21, Rb, and cyclin D1 was considered to be related to dysplastic progression and advancement of malignancy in GEPLs. Therefore, immunohistochemical studies of cell cycle related proteins and a combined analysis may be useful for estimating and following up cases of GEPLs.
Carcinogenesis ; Cell Cycle ; Cyclin D1* ; Cyclins* ; Humans ; Retinoblastoma Protein

No abstract available.
Breast Neoplasms* ; Breast* ; Cyclin D1* ; Cyclins* ; Survival Rate*

BACKGROUND AND OBJECTIVES: The p16, cyclin D1, their partners Cdk4/Cdk6, and pRb constitute a G1 regulatory pathway commomly targeted in tumorigenesis. Genetical, immunochemical, and functional analyses show abnormalities of this pathway in various tumors including head and neck squmaous cell carcinoma. To investigate the clinicopathologic meanings of p16 protein and the relationship between p16 and cyclin D1 in head and neck squmous cell carcinoma. MATERIAL AND METHOD: Formalin-fixed paraffin-embeded tumor materials that were obtained from 37 patient with head and neck squmaous cell carcinoma were analyzed by immunohistochemical staining method using antiserum that were directed against p16 and cyclin D1. RESULTS: 1) Deletion of p16 was found in 67.6% (25/37) of the patients with head and neck squamous cell carcinoma. The deletion was not associated with the clinicopathologic parameters (eg. T and N stages, cell differentiation). 2) Deletion of p16 protein and overexpression of cyclin D1 were identified in 76% (28/37) of the patients with head and neck squmaous cell carcinoma. But deletion of p16 was not affected by the overexpression of cyclin D1 in head and neck squmaous cell carcinoma. CONCLUSION: Deletion of p16 and overexpression of cyclin D1 were identified in head and neck squmaous cell carcinoma. These may abrogate the G1 regulatory pathway. These data suggested that combination of these abnormalities may be important in head and neck turmorigenesis.
Carcinogenesis ; Carcinoma, Squamous Cell* ; Cyclin D1* ; Cyclins* ; Head* ; Humans ; Neck*

PURPOSE: P53 and cyclin D1 have been evaluated as a prognostic marker in papillary thyroid carcinoma (PTC). However, the relationship between p53/cyclin D1 and PTC prognosis has not yet been confirmed. Therefore, we investigated the relationship between p53/cyclin D1 and PTC prognostic factors. METHODS: 919 patients with PTC were enrolled. Immunohistochemistry slides were reviewed for p53 and cyclin D1 immunoreactivity. Patients were classified into two groups according to the p53 and cyclin D1 grade: negative for < or =5% and positive for >5%. Medical records were reviewed to evaluate the prognostic factors, lymph node metastatic ratio (LNMR), and MACIS score. We analyzed patients based on p53/cyclin D1(-/-), p53/cyclin D1(-/+), p53/cyclin D1(+/-), p53/cyclin D1(+/+) separately for evaluation of independent effect of p53 and cyclin D1. RESULTS: Mean age of the patients was 49.73 years (range 15~87), and tumor size was 1.19 cm (range 0.1~5.0). P53 was positive in 809 (88.0%) and cyclin D1 was positive in 748 (81.4%). Positivity of p53 and cyclin D1 were correlated (r=0.448). There was no statistical significance in MACIS score. Positivity of p53 and cyclin D1 were related with larger tumor size, older age, early T stage, more tumor capsulation, and female. LNMR was higher in p53/cyclin D1(+/-) than p53/cyclin D1(-/-) (P=0.036), p53/cyclin D1(-/+) than p53/cyclin D1(-/-) (P=0.034), and p53/cyclin D1(+/+) than p53/cyclin D1(-/-) (P=0.007). CONCLUSION: There was no consistent relationship between p53/cyclin D1 and worse prognostic factors of PTC. However, LNMR was higher in p53(+) and cyclin D1(+) cases independently, much more in p53/cyclin D1(+/+) than p53/cyclin D1(-/-).
Cyclin D1* ; Cyclins ; Female ; Humans ; Immunohistochemistry ; Lymph Nodes ; Medical Records ; Prognosis ; Thyroid Neoplasms*

BACKGROUND: Inactivation of the retinoblastoma protein (pRb) is a mechanism by which tumor cells can subdue normal growth control. Among the molecules involved in control of pRb phosphorylation, cyclin D1 and cyclin E have been found to be deregulated and overexpressed in various types of cancers. METHODS: Immunohistochemical stains for pRb, p16, cyclin D1 and cyclin E were performed in 73 cases of infiltrating duct carcinomas of the breast. In addition to analysis of their expression rates, the relationships between their expressions and the clinicopathologic parameters were evaluated. RESULTS: pRb, p16, cyclin D1 and cyclin E were positive in 64.7% (44 out of 68 cases), 24.6% (15 out of 61 cases), 43.8% (32 out of 73 cases) and 61.6% (45 out of 73 cases), respectively. Their expression rates were not significantly associated with clinicopathologic prognostic factors. 33 out of 38 cases with p16-negative reactions were pRb positive, while 10 out of 15 cases with pRb-negative reactions were p16 positive. There was a significant inverse relationship between pRb and p16 expressions (P<0.005). 25 out of 32 cases with cyclin E-positive reactions were cyclin D1-positive, and 25 out of 45 cases with cyclin D1-positive reactions were cyclin E-positive. A statistically significant association was observed between cyclin D1 and cyclin E expressions (P<0.05). CONCLUSIONS: The main mechanism during tumorigenesis of breast carcinoma depends on the cyclin D1/p16/pRb pathway, but cyclin E might play a role in the absence of cyclin D1. The inverse correlation between the pRb and p16 expressions may represent one of the important mechanisms in tumorigenesis, as well.
Breast Neoplasms ; Breast* ; Carcinogenesis ; Coloring Agents ; Cyclin D1* ; Cyclin E* ; Cyclins* ; Phosphorylation ; Retinoblastoma ; Retinoblastoma Protein

BACKGROUND: Cyclin D1 expression is closely related with ER in breast cancer. We conducted this study to evaluate whether therapeutic response to tamoxifen is varied with levels of cyclin D1 expression in ER positive breast cancer patients. MATERIALS AND METHODS: Immunohistochemical assay for cyclin D1 protein was performed in 66 patients tasted with tamoxifen for more than 2years. Patient survival and correlation between cyclin D1 expression and biologic data of the patients were analyzed RESULTS: Cyclin D1 expression was detected in 46 (69.7%) and significantly reduced in poorly differentiated cancer (p=0.023). Cyclin D1 expression was high in the tumors expressing Myc (15/15 vs 31/51; p=0.002), and was markedly increased in the tumors in which p27Kip1 expression was repressed (30/38, 78.9%). However, the difference was not statistically significant (p=0.051). There was no significant relationship between cyclin D1 expression and S-phase. Patients with tumors expressing cyclinD1 showed better disease free survival and overall survival but the difference was not statistically significant. CONCLUSIONS: Cyclin D1 expression was associated with cell differentiation but not useful in discriminating high risk group with tamoxifem treatment. Cyclin D1 may have a role in process other than cell cycle regulator in ER positive breast cancer, such as differentiation signal.
Breast Neoplasms ; Cell Cycle ; Cell Differentiation ; Cyclin D1* ; Cyclins* ; Disease-Free Survival ; Estrogens* ; Humans ; Prognosis ; Tamoxifen*

OBJECTIVE: This study was carried out to investigate the relationship between DNA ploidy, S-phase fraction (SPF), expression of cyclin A and clinical prognostic factors including stage, grade, CA-125 and residual tumor size in epithelial ovarian cancer, and to evaluate the association between DNA ploidy, SPF, expression of cyclin A and 3-year survival. METHODS: Study group consisted of 31 cases of epithelial ovarian cancer, 10 of borderline ovarian tumor and 5 of benign ovarian tumor diagnosed at the department of Obstet. and Gynecol. in Yonsei University College of Medicine, Seoul, Korea from Feb. 2000 to Jan. 2003. All patients underwent staging-laparotomy and postoperative chemotherapy. The level of CA-125 was assessed after 6th postoperative chemotherapy with cut-off value of 35 U/mL. DNA ploidy and SPF were evaluated by flow-cytometry of fresh ovarian tissue obtained at the operative field. The expression of cyclin A was evaluated by immuno-histochemical stain. Expression of 5% was considered as positive. Statistical analysis was done by two-sample t-test, chi-square test, and Kaplan-Meier survival curve using SPSS ver 11.0 software. RESULTS: In 46 ovarian tumors aneuploidy, SPF and expression of cyclin A were significantly higher in epithelial ovarian cancer as compared with benign and borderline tumors (p=0.004, 0.001, 0.001, respectively). Number of aneuploidy, SPF and expression of cyclin A were significantly higher in patients with higher grade, more advanced stage, higher level of CA-125 (more than 35 U/mL) and more than 2 cm of residual tumor size (p=0.004, 0.009, 0.05, 0.002 in aneuploidy; p=0.06, 0.01, 0.04, 0.007 in SPF; p=0.03, 0.004, 0.06, 0.02 in cyclin A). Aneuploidy and expressions of more than 10% of SPF and cyclin A were also associated with poorer overall survival (p=0.02, 0.02, <0.0001, respectively). Significantly positive correlations were observed among these factors. CONCLUSION: Number of aneuploidy, percentage of SPF and expression of cyclin A were higher in more advanced stage, higher grade, higher CA-125 and more than 2 cm of residual tumor size and associated with poorer overall survival. Thus DNA flow-cytometry and estimation of expression of cyclin A may provide major information about prognosis of disease in epithelial ovarian cancer patients.
Aneuploidy ; Cyclin A* ; Cyclins* ; DNA* ; Drug Therapy ; Humans ; Korea ; Neoplasm, Residual ; Ovarian Neoplasms* ; Ploidies ; Prognosis ; Seoul