Mutant or aberrant regulation of expressing products of p53 gene results in losing its tumor suppressive function,which is often seen in many malignancies,including breast cancer.Oncoprotein MDM2 plays a primary role in regulating P53,and these two form an automregulatory feed back loop.mdm 2/p53 pass way performs important function in development,progression,therapy and prognosis of breast cancer.Besides,more and more studies show that some other molecular markers in breast cancer,such as PI3K/Akt/mTOR, p14ARF, and Her2/neu can regulate this passway unneglectedly.The purposeof this reviewis to summarize not only the relations betweenmdm 2/p53 passway and pathological charac-ters,therapy and prognosis of breast cancer,but also the relations of this passway with some other molecular proteins in breast cancer.
Background Human epidermal growth factor 2 （HER2） is one of the most important prediction factors, but only 25%-30% of breast cancer patients HER2 are positive. It is unknown whether there are other molecular markers that could be used to predict prognosis and recurrence in HER2 negative patients.This study investigated correlations of cyclin A2 and HER2 levels with clinical outcomes in 281 patients with invasive breast cancer in order to identify whether cyclin A2 can serve as a prognostic factor in HER2 negative patients. Methods Immunohistochemical staining was used to detect cyclin A2 and HER2 expression in 281 patients. Cyclin A2 and HER2 gene amplifications were analyzed using gene analysis and RT-PCR in 12 patients. Risk and survival estimates were analyzed using Log-rank, Kaplan-Meier, and Cox regression analysis; cyclin A2 and HER2 consistency with survival were analyzed using Kappa analysis. Results Patients with higher cyclin A2 and HER2 expressions had significantly shorter disease-free survival periods （P=0.047 and P=-0.05, respectively）. Kappa analysis performed that cyclin A2 and HER2 showed a low Kappa index （kappa=0.37）, allowing us to conclude that cyclin A2 and HER2 detect different pathologies. Gene analysis and RT-PCR showed that cyclin A2 was upregulated in patients with early relapse; the average increase was 3.69-2.74 fold. Conclusions Cyclin A2 and HER2 are associated with proliferation and high recurrence, particularly when combined. Cyclin A2 is easily detected by nuclear staining and might be a useful biomarker for recurrence risk in HER2 negative patients.
LI Hui-pingJI Jia-fuHOU Kuan-yongLEI Yu-taoZHAO Hong-meiWANG JingZHENG JieLIU Jian-yingWANG Mo-peiXIAO YuWANG You-fanLU You-yongSUN Yan
