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p21WAF1/CIP1 protein expression in primary ovarian cancer
G Ferrandina1, A Stoler, A Fagotti
1Department of Gynecology and Obstetrics, Catholic University, Rome, Italy.
Abstract:
p21WAF1/CIP1 protein is a cyclin-dependent kinase inhibitor, able to prevent the CDK2/cyclin E induced retinoblastoma protein (pRB) phosphorylation, thus inhibiting cell cycle progression at G1 phase. p21WAF1/CIP1 protein levels were examined in a series of 102 ovarian tissue samples including normal ovary, primary ovarian tumors, omental metastasis, recurrent disease and residual tumor after chemotherapy exposure, by Western blot analysis. The association of p21WAF1/CIP1 status with clinicopathological parameters and clinical outcome was also investigated. p21WAF1/CIP1 protein was detectable in 76 out of 102 (74%) ovarian tissue samples. We observed a significant trend of p21 levels to gradually increase from normal ovarian tissues (median 0 a.u.) through primary ovarian cancers (median 0.19 a.u.), omental metastases (median 0.33 a.u.) and recurrence of disease (median 0.44 a.u.) (p=0.015). In the group of stage III-IV ovarian cancer patients, p21-positive cases showed a more favourable prognosis with respect to p21-negative cases: the 3-year time to progression (TTP) rate was 58% for p21-positive compared with 33% of p21-negative cases (p=0.036). In conclusion, p21WAF1/CIP1 expression levels seem to be correlated with tumor status at the time of diagnosis and can predict TTP in a selected group of patients.
Insights
The p21WAF1/CIP1 protein, a cell cycle inhibitor, increases with ovarian cancer progression. Higher p21WAF1/CIP1 levels correlate with better prognosis and longer time to progression in advanced ovarian cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Cycle Regulation
Background:
- The p21WAF1/CIP1 protein acts as a cyclin-dependent kinase inhibitor, crucial for cell cycle arrest at the G1 phase by preventing retinoblastoma protein (pRB) phosphorylation.
- Understanding p21WAF1/CIP1 expression is vital for assessing ovarian cancer progression and patient outcomes.
Purpose of the Study:
- To investigate the expression levels of p21WAF1/CIP1 protein in various stages of ovarian tissue, including normal, primary tumors, metastases, and recurrent disease.
- To determine the association between p21WAF1/CIP1 status and clinicopathological parameters.
- To evaluate the predictive value of p21WAF1/CIP1 expression on clinical outcomes, specifically time to progression (TTP).
Main Methods:
- Western blot analysis was employed to quantify p21WAF1/CIP1 protein levels in 102 ovarian tissue samples.
- Samples included normal ovaries, primary ovarian tumors, omental metastases, recurrent disease, and residual tumors post-chemotherapy.
- Statistical analysis was performed to correlate p21WAF1/CIP1 levels with clinicopathological data and patient prognosis.
Main Results:
- p21WAF1/CIP1 protein was detected in 74% of the analyzed ovarian tissue samples.
- A significant increasing trend in p21WAF1/CIP1 levels was observed from normal ovarian tissues to primary cancers, omental metastases, and recurrent disease (p=0.015).
- In stage III-IV ovarian cancer patients, p21-positive cases demonstrated a significantly more favorable 3-year time to progression (TTP) rate (58%) compared to p21-negative cases (33%) (p=0.036).
Conclusions:
- p21WAF1/CIP1 expression levels are significantly correlated with the stage of ovarian tumor at diagnosis.
- p21WAF1/CIP1 status serves as a potential predictive biomarker for time to progression in advanced ovarian cancer.
- Further research into p21WAF1/CIP1's role could inform therapeutic strategies for ovarian cancer.
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