Ki67Expression and Its Clinical Significance in Early Breast Cancer
|Keywords||Ki67 immunohistochemistry cytoplasmic nuclear breast cancer prognosis clinicopathologic parameters|
Background:The proliferation biomarker Ki67is one of the most reliable indexes to monitor proliferative the proliferative activity of tumor cells, which can apace reflect the proliferative ratio of malignant tumors, thereby associated with their progress, metastasis and prognosis. Generally, Ki67is to be located in the nucleus of the cells when detected by immunohistochemistry. In recent years, cytoplasmic Ki67immunoreactivity has been investigated in a number of histopathological researches. But the mechanism is not clearly enough.Objective:The aims of the present study were to1. Study on the expression and distribution of Ki67in patients with early breast cancer;2. Evaluate the interactions of Ki67(cytoplasmic/nuclear) and the clinicopathologic parameters in breast cancer patients, and investigate their clinical significance.Patients and methods:1. The patients who received modified radical mastectomy in2007in the first affiliated hospital of soochow university were included in our study. Ki67(MIB-1clone) proliferation index and pattern of immunoreactivity was detected and other clinicopathologic parameters was got from the pathological reports. To follow-up the patients till June30th,2012, we recoded the disease relapse and the survival status.2. SPSS for Windows version17.0was used for all statistical analysis. Survival analysis was used to judge the prognostic value of cytoplasmic and nuclear Ki67and describe the survival curves. P<0.05was considered statistically significant. Meanwhile, the correlativity between Ki67and other clinicopathologic parameters were also in the analysis.Results:1.76(84.4%) of90assessable tumors expressed nuclear Ki67, of which21patients were defined as high expression (≥14%), and the high expression rate was27.6%. And of all these samples,17(18.9%) of85assessable tumors expressed cytoplasmic Ki67.2. As for the related factors with nuclear Ki67, ER and PR expression were negatively correlated with Ki67, and HER2expression was positively correlated with the Ki67(P<0.05). While, the other factors had no relationship with nuclear Ki67, including age, tumor size, nodal stage and histological grade. Analyzing the survival curves of DFS and OS of nuclear Ki67, we can find that the patients’ survival of high expression was significantly lower than those of low expression, and the curves separated clearly (P<0.05). In the Cox regression model, the results showed that nuclear Ki67had a significant influence on the prognosis of breast cancer (DFS:HR2.94, P<0.05&OS:HR4.00, P<0.05), and there was important meaning in multiple analysis, which suggested that the nuclear Ki67maybe be an independent prognostic factor.3. The cytoplasmic Ki67expression wasn’t associated with the other clinicopathologic parameters (P>0.05). And in the Cox regression model of cytoplasmic Ki67, our research showed that the cytoplasmic Ki67didn’t have effect on the survival of breast cancer patients, neither5-year DFS nor OS (P>0.05).4. The results of researching on the effect of breast cancer biological characteristics on the prognosis of breast cancer were that nodal stage independently affected the prognosis of breast cancer (P<0.05); age also had some effect on the prognosis, but it was not an independent factor. Tumor size had some impact on the DFS and OS, but the difference was not statistically significant (P>0.05). However, ER, PR and HER2were of no effect in the present study.Conclusions:1. Nuclear Ki67significantly affected the prognosis of breast cancer, and was an independent prognostic factor. And its expression was positively correlated with ER and PR, negatively correlated with HER2.2. Cytoplasmic immunoreactivity of Ki67may not be important to evaluate the prognosis of invasive breast cancer. It may be just a functional phenomenon in the tumor cells. And its expression wasn’t associated with the other clinicopathologic parameters.3. Age and node stage were the prognostic factors of breast cancer, and the later was an independent one.