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The Expression and Progrosis Analysis of Cell Proliferation Marker Ki-67 in Breast Cancer

Author: JiaMing
Tutor: WeiSuJu
School: Hebei Medical University
Course: Oncology
Keywords: Breast Cancer Ki-67 Clinical and pathological features Prognosis COX proportional hazards model
CLC: R737.9
Type: Master's thesis
Year: 2011
Downloads: 104
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Abstract


Objective: Breast cancer is one of the most common malignancy in women, and rank first female malignancy in the morbidity and mortality in Western countries. Its incidence is second only to cervical cancer in our country. In recent years, progress has been achieved in the early diagnosis and treatment, but the mortality rate is no noticeable decline. With the continuous development of molecular biology techniques and their application in breast cancer research, has identified more and more to reflect the biological markers of prognosis. Ki-67 is expressed in proliferating cells in a nuclear antigen associated with cell mitosis. High expression of Ki-67 in a variety of tumor tissue, the short half-life of, degrade rapidly out of the cell cycle characteristics so that it has become the most reliable indicators of detection of tumor cell proliferation activity. Ki-67 expression level of the evaluation of cell proliferative state, study the biological behavior of the tumor, determine the harmfulness of great significance. In this study, the data of 730 cases of post-operative breast cancer cases under review, and application of non-parametric tests, COX proportional hazards model, such as a variety of statistical methods to study the relationship between ki-67 expression with clinicopathological characteristics and prognosis analysis . Methods: The study collected the Fourth Hospital of Hebei Medical University Branch (breast surgery) were treated between January 1, 2008 to 2008, the result of a clear molecular markers (ER, PR, and HER-2 ki-67, AR) and a clear pathological diagnosis Ⅰ - Ⅲ phase with operable breast cancer cases, the presence of distant metastasis cases eliminate the initial treatment, a total of 730 cases of surgical patients. At least one follow-up (telephone follow-up, and nosocomial review), the follow-up time for the deadline to 2010 or were lost to follow all cases, the date of death. The mean operative time as a starting point to patients died, lost or until the last follow-up time for the end of. Ki-67 positive cells were defined as follows: nuclei appeared brown particles randomly selected 10 fields per field under high magnification (× 400) 100 tumor cells, calculate the percentage of positive cells accounted for the total number of tumor cells is Ki-67 proliferation index. Ki-67 positive expression rate of less than 10% is defined as \higher than 50% is defined as \Disease-free survival (Disease Free Survival, DFS) defined radical surgery to tumor recurrence or cause of death in patients due to disease progression. Overall survival (Overall Survival OS) is defined as a disease (cancer) diagnosed until it died in the time up to a variety of reasons, the most reliable tumor endpoint. To the end of time, disease-free survival in patients with 585 cases, 102 cases of patients with disease progression, and death of the 43 cases. Follow-up data entry SPSS13.0 statistical package accurate statistics. This study from the relationship between the ki-67 molecular markers, before and after menopause Ki-67 expression, different, four aspects of the relationship between ki-67 and the clinical and pathological features and ki-67 and prognosis of ki -67 conduct a more comprehensive analysis and evaluation. The X2 test count data on this group, ranked data using non-parametric tests, using the Spearman rank correlation analysis of the relationship between two variables. The survival rate calculated using the product-limit method (Kaplan-Meier), Application Log-rank test comparison between groups. Clinicopathological factors and postoperative treatment quantify assignment, disease-free survival (DFS) and overall survival (0S) single factor using Cox proportional hazards model, multivariate analysis, independent prognostic draw between the two factor. All data are P lt; 0.05 as statistically significant difference. Results: 1 Ki-67 positive expression rate: in the full corrective .730 patients information, ki-67 positive expression rate was 95.5%, which, of ki-67 () the proportion of 40.4%, ki-67 () proportion to 42.7%, ki-67 () the proportion was 12.4%. The 2 survival: the 1 -, 2 - and 3-year overall survival of all patients was 98.5%, 95.3%, 94.1%; whole group of patients with 1 -, 2 - and 3-year disease-free survival rate was 92.5%, 90.0%, and 80.1%. The relationship between the three molecular markers: ki-67 was negatively correlated with the expression of ER and PR expression was negatively correlated with the HER-2 expression was positively correlated with AR expression was positively correlated (P lt; 0.05). 4 before and after menopause, the differential expression of various molecular markers: where ER, HER-2 in the expression before and after menopause no difference; ki-67 PR menopause expression differences (P lt; 0.05) of ki-67 post-menopausal positive expression rate in premenopausal positive expression rate lower than pre-menopausal PR postmenopausal. 5 Ki-67 expression with clinicopathological features of the relationship between: ki-67 expression and tumor size, histological grade, vascular invasion, clinical stage are related (P lt; 0.05); independent of but with lymph node metastasis ( P gt; 0.05). LVSI appear more common in the Ki-67 positive expression group. Higher Ki-67 positive expression rate, the larger the tumor, the worse the histological, clinical stage later. 6 ki-67 expression and prognosis: of ki-67 expression is divided into three groups: ki-67 positive expression rate lt; 10% for the low expression group (ki-67); ki-67 positive expression rate of between 10% -50% expression group (ki-67); ki-67 positive expression rate gt; 50% for the high expression group (ki-67). Respectively DFS, OS for horizontal axis, the survival rate for the vertical axis drawn Kaplan-Meier survival curves: DFS between different ki-67 expression corrective survival curves are different, ki-67 positive expression rate higher disease survival of the shorter (P lt; 0.05). Ki-67 expression has no effect on 0S. COX univariate analysis of disease-free survival DFS: ki-67 expression, the number of axillary lymph node metastasis, clinical stage, ER and PR expression, postoperative adjuvant radiotherapy after endocrine therapy for impact with operable breast cancer significant factors in patients with DFS (P lt; 0.05). Multivariate analysis showed that: ki-67 expression, axillary lymph node metastases, clinical stage, endocrine therapy for DFS independent prognostic factor (P lt; 0.05). 8 on the overall survival of 0S COX univariate analysis showed that: the number of axillary lymph node metastasis, clinical stage, postoperative radiotherapy, endocrine therapy after effects can be significant factors for breast cancer patients with OS (P lt; 0.05). Multivariate analysis showed that: the number of axillary lymph node metastases, endocrine therapy as an independent prognostic factor of OS (P lt; 0.05). Conclusions: 1 ki-67 with ER and PR expression was a negative correlation of HER-2, AR expression was positively correlated. 2 ki-67, PR expression in menopause, ki-67 post-menopausal positive expression rate in premenopausal PR postmenopausal positive expression rate lower than pre-menopausal. The LVSI appear more common in the Ki-67 positive expression group. Higher Ki-67 positive expression rate, the larger the tumor, the worse the histological, clinical stage later. DFS survival curves between 4 different ki-67 expression group differences, ki-67 positive expression rate is higher the shorter disease-free survival. Ki-67 expression, the OS does not have any effect. 5 independent prognostic factors affect breast cancer disease-free survival DFS ki-67 expression, axillary lymph node metastases, clinical stage, endocrine therapy. The impact of breast cancer overall survival OS independent prognostic factor for the number of axillary lymph node metastases, endocrine therapy. 7 combined with the relationship between the ki-67 with clinical and pathological features and prognosis of clear ki-67 as an adverse prognostic factors in breast cancer.

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