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Expression of Phosphorylated Protein Kinase B and PTEN in Ovarian Epithelial Cancers

Author: ChengJia
Tutor: QiaoYuHuan
School: Zhengzhou University
Course: Obstetrics and Gynaecology
Keywords: Epithelial ovarian cancer AKT PTEN Immunohistochemistry
CLC: R737.31
Type: Master's thesis
Year: 2007
Downloads: 154
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Abstract


Background and Purpose epithelial ovarian cancer (ovarian cancer) is the highest mortality of gynecologic malignancies has discovered later, early metastasis, and poor prognosis, its pathogenesis remains unclear. Recent studies found that many types of tumors, including ovarian cancer, the development of abnormal signal transduction pathways, signal transduction pathway the abnormal activation of oncogenes, inactivation of tumor suppressor genes, and (or) affect tumor malignant behavior and an important prognostic factor. Protein kinase B (PKB), also known as AKT, is a serine / threonine kinase, is a signal transduction protein. PKB family members have found that three kinds: PKBα / β / γ (AKT-1/2/3). AKT is activated, it can phosphorylation and apoptosis-related substrate proteins play an important role in cancer and chemotherapy resistance. 3 - carboxyl phosphatidylinositol kinase (PI3K) is a heterodimer of the catalytic subunit (P110) and the regulatory subunit (P85), an important target genes AKT, which constitute the cell external stress response The process of promoting cell growth, inhibition of apoptosis and maintain the important features of the cells of the signal transmission chain. The study shows that the the PI3K/AKT pathway abnormalities with a variety of tumors, including gynecological tumorigenesis, development, invasion, metastasis, angiogenesis, and resistance to chemotherapy. Tensin homologue on chromosome 10 is missing phosphatase gene (phosphatase and tensin homologue deleted on chromosome 10, PTEN) is found so far only has dual phosphorylation of the lipid phosphatase and protein phosphatase activity of tumor suppressor genes. Studies have shown that PTEN reduce AKT activity by inhibiting the PI3K/AKT signaling pathway plays a negative regulatory role of cell proliferation. The lack of PTEN expression abnormal activation of the PI3K/AKT pathway activation of AKT phosphorylation of AKT (p-AKT) allows tumor cells to evade apoptosis and abnormal cell proliferation and differentiation, thereby contributing to the occurrence of cancer. Domestic and international research on ovarian cancer has only detect p-AKT and PTEN protein expression is raised or lowered, and abnormal activation of the PI3K/AKT pathway and PTEN protein expression deletion reported still less with the prognosis of patients with ovarian cancer. To this end, the present study, immunohistochemical methods to investigate the p-AKT and PTEN protein expression in ovarian cancer tissues and their relationship, and analyze the relationship between the two and the prognosis of patients with ovarian cancer, aimed at further deepening the pathogenesis of ovarian cancer understanding and provide a theoretical basis for the prognosis and treatment of ovarian cancer. Materials and Methods Department of Pathology, the First Affiliated Hospital of Zhengzhou University, from January 2001 to January 2006 inpatient surgical specimens archived paraffin blocks. Were selected specimens of 124 cases, including 12 cases of normal ovarian tissue (normal group), from the same period due to uterine fibroids surgical specimens; benign ovarian epithelial tumors in 20 patients (benign group, serous cystadenoma 13 cases mucinous cystadenoma 7 cases); borderline ovarian tumors in 12 patients (borderline group, including eight cases of borderline serous cystadenoma, borderline mucinous cystadenoma four cases); 80 cases of ovarian cancer tissue (ovarian cancer group, including 59 cases of serous adenocarcinoma, mucinous cystadenocarcinoma 21 cases). Patients aged 19 to 72 years old, with a median age of 45.5 years. All age groups, the difference was not statistically significant (P> 0.05). Ovarian cancer group, histological grade: (G 1 ), moderately differentiated (G 2 ), 52 cases of poorly differentiated (G 3 ) 28; clinical stage: the standards of the International Federation of Gynecology and Obstetrics (FIGO, 2000), 36 cases of stage I / II, III / Ⅳ 44 cases (Ⅳ period only one cases of umbilical metastases patients); lymph node metastasis in 29 cases, 51 cases without lymph node metastasis. All patients had initial issuance, did not receive preoperative radiotherapy and chemotherapy. Follow-up by phone or to the hospital review in the form of ovarian cancer patients, up from 4 to 60 months, follow-up ended in May 2006. This study used immunohistochemical methods to detect p-AKT and PTEN protein expression in the above-mentioned organizations, to explore the relationship between the expression of both ovarian cancer clinical pathological factors and their mutual relations, and analysis of the relationship between both and the prognosis of patients with ovarian cancer . Statistical analysis using SPSS 13.0 statistical software for data processing, p-AKT and PTEN protein expression and clinicopathological factors χ 2 test, Spearman rank correlation analysis between the two correlations. Application Kaplan-Meier method for univariate survival analysis and Cox proportional hazards model for survival multivariate analysis, significant difference test using the Log-Rank test. Α = 0.05 as the difference was statistically significant level of inspection. Results 1. p-AKT and PTEN protein expression in different types of ovarian tissue. P-AKT and PTEN protein expression rates were 50.0% (44/80) in 80 cases of ovarian cancer tissues, 12 cases of borderline ovarian tumors, 20 benign ovarian epithelial tumors and 12 cases of normal ovarian tissue. 25.0% (3/12), 10.0% (2/20) and 8.3% (1/12) and 45.0% (36/80), 66.7% (8/12), 80.0% (16/20) and 100% (12/12). p-AKT and PTEN expression differences between the various types of ovarian tissue overall statistically significant (P = 0.000). The line χ 2 split p-AKT protein expression in ovarian cancer group was significantly higher than the expression of the benign group and the normal group, the difference was statistically significant (P <0.01); positive for PTEN protein expression was significantly lower than the benign expression of the group and the normal group, the difference was statistically significant (P <0.01). 2. p-AKT and PTEN protein relationship between clinicopathological factors and ovarian cancer. Highly differentiated (G 1 G 2 ) ovarian cancer group p-AKT protein expression was 44.2% (23/52), significantly lower than the poorly differentiated ( G 3 ) ovarian cancer group 75.0% (21/28). Expression of differences between the two groups was statistically significant (P = 0.008). PTEN protein in highly differentiated (G 1 G 2 ), the positive expression rate of ovarian cancer group 55.8% (29/52), significantly higher than poorly differentiated ( G 3 ) ovarian cancer group 25.0% (7/28). Differences of expression between the two groups was statistically significant (P = 0.008). Ⅰ / Ⅱ (early) ovarian cancer group p-AKT protein positive expression rate was 33.3% (12/36), significantly lower than the stage Ⅲ / Ⅳ (advanced) ovarian cancer group 81.8% (36/44). Expression of differences between the two groups was statistically significant (P = 0.000). PTEN protein expressed in the positive phase Ⅰ / Ⅱ ovarian cancer group was 52.8% (19/36), significantly higher than Ⅲ / Ⅳ ovarian cancer group 27.3% (12/44). Differences of expression between the two groups was statistically significant (P = 0.020). P-AKT protein lymph node metastasis in ovarian cancer patients, the positive expression rate was 62.1% (18/29), significantly higher than those without lymph node metastasis in ovarian cancer patients, 31.4% (16/51). Expression of differences between the two groups was statistically significant (P = 0.008). PTEN protein positive expression of lymph node metastasis in ovarian cancer group was 31.0% (9/29), significantly lower than those without lymph node metastasis in ovarian cancer group 68.6% (35/51). Differences of expression between the two groups was statistically significant (P = 0.001). <50 years and ≥ 50 years old, serous ovarian carcinoma and mucinous ovarian cancer group and the presence of ascites, p-AKT and PTEN protein expression was no significant difference (P> 0.05). 3. Correlation of p-AKT and PTEN protein expression in ovarian cancer tissue. were positive for p-AKT and PTEN protein expression by 11 cases were negative for 11 cases, p-AKT protein expression and PTEN protein negative expression of the 33 cases, p-AKT protein negative expression of PTEN The expression for the 25 cases. The Spearman rank correlation analysis, p-AKT and PTEN protein expression in ovarian cancer tissues was negatively correlated (r = -0.444, P = 0.000). 4. P-AKT and PTEN protein in ovarian cancer tissue relationship with the prognosis of patients with ovarian cancer. To the end of the follow-up, 62 patients were followed up cases, 12 cases of survivors, the cumulative survival rate was 21.6%, the median survival time was 15 months. 32 cases of patients with negative expression of p-AKT survival 8 cases, 4 cases of 32 cases of patients with positive expression of p-AKT survival, the cumulative survival rates were 27.3% and 15.6%, the median survival time was 25 months and 15 months the two groups, the difference was statistically significant (P = 0.00079). 33 cases of patients with negative expression of PTEN survived three cases, 31 cases of PTEN expression in patients surviving nine cases, the cumulative survival rates were 9.1% and 34.7%, the median survival time was 9 months and 28 months, the two groups , the difference was statistically significant (P = 0.000). P-AKT and PTEN protein expression, they are divided into four groups: p-AKT-/PTEN, p-AKT-/PTEN- p-AKT / of PTEN-and p-AKT / of PTEN. Survival analysis by the Log-Rank test, the difference was statistically significant (P = 0.000) between the four groups. Which the cumulative survival rate of the patients with the highest p-AKT-/PTEN group (35%), with a median survival time of 29 months, the cumulative survival rate of the p-AKT / PTEN-group of patients with the lowest (8.7%), the median survival time for eight months. Survival by the Kaplan-Meier method of single factor analysis, clinical stage, histological grade, lymph node metastasis, p-AKT protein expression and PTEN protein expression with ovarian cancer prognosis (P <0.05). Survival multivariate analysis by the Cox proportional hazards model, PTEN and clinical staging is an independent risk factor for ovarian cancer prognosis (P <0.05). Conclusion 1. Abnormal activation of AKT protein missing the incidence of ovarian cancer and PTEN protein expression, development, invasion and metastasis. 2. Negative correlation between the expression of p-AKT and PTEN protein in ovarian cancer tissue. 3. p-AKT protein related to the prognosis of patients with ovarian cancer, but not an independent risk factor for ovarian cancer prognosis and PTEN and clinical stage independent prognostic factors in patients with ovarian cancer, suggesting that PTEN and clinical staging as an evaluation of ovarian prognostic indicator in patients with cancer.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Female genital tumors > Ovarian tumors
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