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Purpose To study the expression of p53, p21 and Cdk1/p34cdc2 in the laryngeal cancer and its margin tissues and to ex-plore their relationship with local recurrence of laryngeal cancer. Methods A total of 85 patients with early laryngeal cancer were se-lected randomly during 2004 to 2010 in Tangshan Union Hospital, Hebei, China. SP immunohistochemical method was used to detect the expression of p53, p21 and Cdk1/p34cdc2 in the tumor and margin tissues. Pathological data were collected for follow-up. Results In more than 2 years of follow-up study, 14 of 85 patients with laryngeal cancer presented with recurrence (recurrent group), while 71 patients without recurrence (none recurrent group). The positive rate of p53 protein in laryngeal cancer and its margin tissues was 60. 0% and 36. 5%, respectively, the positive rate of p21 protein in laryngeal cancer and its margin tissues was 38. 8% and 21. 2%, respectively. The positive rate of Cdk1/ p34cdc2 in laryngeal cancer and its margin tissues was 70. 6% and 29. 4%, respectively. p53 protein in the surgical margin of the recurrent group and non recurrent group was 71. 4% and 29. 6% (P = 0. 003), that of p21 was 50. 0% and 15. 5%, (P =0. 004) and Cdk1/ p34cdc2 was 57. 1% and 23. 9% (P =0. 013), respectively. There was no correlation between expression of p53 with p21 protein and Cdk1/ p34cdc2 protein(P > 0. 05). Conclusion p53, p21 and Cdk1/ p34cdc2 may be involved in the occurrence, development and recurrence of laryngeal squamous cell carcinoma. Overexpression of p53, p21 and Cdk1/ p34Cdc2 in the surgical margin is closely related to local recurrence of laryngeal cancer.
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Objective: To study the expression of p34cdc2 and cyclin B1 in human cervical carcinoma, and the relationship between their expression and clinicopathologyical features of cervical cancer. Methods: A quantitative real-time reverse transcription polymerase chain reaction and Western blotting assay were used to analyze the expression levels of p34cdc2 and cyclin B1 mRNA and protein, respectively, in fresh invasive cervical cancer (n = 62) and control cervical tissues (n = 15). Results: The expression levels of p34cdc2 and cyclin B1 mRNA and protein were significantly higher in cancer tissues than those in control cervical tissues (P = 0.004, P = 0.013; P = 0.016, P = 0.029), and mainly displayed overexpression. Significant positive correlation was found between the expression of p34cdc2 and cyclin B1 mRNA (r = 0.527, P = 0.001) and protein (r = 0.432, P = 0.022) in cervical cancer tissues. A statistical significance was found between the expressions of p34cdc2/cyclin B1 mRNA and lymphatic metastasis in cervical cancer (P = 0.038, P = 0.001). No statistically significant association was found between the age, histological types, the differentiation degree, clinical stages and expression of p34cdc2/cyclin B1 (P > 0.05). Conclusion: p34cdc2 and cyclin B1 are important molecules in regulation of cervical carcinogenesis. Over-expression of p34cdc2/cyclin B1 stimulates cervical cancer cells to overcome G2/ M checkpoint and enter M phase in cell cycle. The high-expression of p34cdc2/ cyclin B1 might become a novel biomarker for studying the mechanism underlying the tumorigenesis and lymphatic metastasis of cervical cancer.
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PURPOSE: Cell cycle progression is regulated by interactions of specific cyclins and cyclin dependent kinases (CDKs) at the G1-S and G2-M checkpoints and cell cycle deregulation plays a major role in carcinogenesis of human cancers. PATIENTS AND METHODS: To investigate the role of cell cycle regulators in the pathogenesis and progression of human gastric cancers, 23 cases of gastric carcinomas were examined for the expression of cyclin B1, p34cdc2, p27(Kip1) and p53 by immunohistochemical methods, and gene expression was correlated with various clinicopathologic findings. RESULTS: Out of 23 cases studied, cyclin B1 was diffusely expressed in 20 cases (87.0%), p34cdc2 in 14 cases (60.9%) and p53 in 12 cases (52.2%), whereas in normal gastric tissues, cyclin B1 and p34cdc2 were weakly expressed and p53 was not expressed. In contrast, p27(Kip1) was expressed in only 8.7% of gastric carcinomas compared with 78.3% of normal gastric tissues. There was correlation between the expression of cyclin B1 and expression of p34cdc2 (p=0.002), between the expression of cyclin B1 and loss of p27(Kip1) (p=0.025), and between the expression of p34cdc2 and loss of p27(Kip1) (p=0.065). In addition, expression of cyclin B1 was correlated with regional lymph node metastasis (p=0.032). CONCLUSION: Our results indicate that cyclin B1 and p34cdc2 are involved in the genesis or progression of gastric cancers. Furthermore, overexpression of cyclin B1 may play an important role in lymph node metastatic potential of gastric cancer. Thus, abnormal expression of cyclin B1 and CDKs, overexpression of p53 and loss of p27(Kip1) expression may play important roles in human gastric carcinogenesis.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , CDC2 Protein Kinase/metabolism , Cyclin B/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Prognosis , Stomach Neoplasms/diagnosis , Tumor Suppressor Protein p53/metabolismABSTRACT
BACKGROUND: Cell cycle progression is governed by cell cycle regulators and inhibitors such as the cyclin dependent kinases (CDK), p27(Kip1), p21(WAF1/Cip1) and p53. The purpose of this study was to correlate expressions of p34(cdc2), p27(Kip1), p21(WAF1/Cip1) and p53 with the various clinicopathologic prognostic parameters of human breast cancers. METHODS: The paraffin-embedded tissue sections from 102 patients with human breast carcinomas were examined by performing immunohistochemical staining. The primary antibodies used for immunohistochemical staining were mouse monoclonal antibody to human p34(cdc2), p27(Kip1), p21(WAF1/Cip1), p53, ER and PR. RESULTS: The expression rates of p34(cdc2), p21(WAF1/Cip1) and p53 were 29.3%, 40.2% and 49.1% in breast carcinomas, respectively. In normal breast tissues, p34(cdc2), p21(WAF1/Cip1) and p53 were not expressed. The p34(cdc2) was expressed in the cytoplasm of cancer cells. The expression rate of p27(Kip1) was 29.3% in breast carcinomas and 100% in normal breast tissues, so the loss of p27(Kip1) expression in breast cancer was noted. The high expression of p21(WAF1/Cip1) in neoplastic cells was associated with the p53 expression (p=0.03). The expression of p27(Kip1) was correlated with that of the progesterone receptor (PR) (p=0.04) and the expression of p21(WAF1/Cip1) was correlated with that of positivity for estrogen receptor (ER) (p=0.04) and PR (p=0.04). No correlation was demonstrated between the mean patient survival and the expression rate of p34(cdc2), p27(Kip1), p21(WAF1/Cip1) and p53. CONCLUSIONS: The loss of the normal cell growth cycle by the abnormal expression of cyclin dependent kinases and their inhibitors and the steroid hormones may play an important role in human breast carcinogenesis. The p53 dependent p21(WAF1/Cip1) pathway, the p27(Kip1) protein loss and the cdc2 overexpression were important in development and progression of human breast cancer.