The Expressions And Correlation Of ERK_1/2/MAPK Signaling Associated Protein And P53 In Ovarian Serous Tumors

Objective:To observe the clinicopathologic characteristics of ovarian serous adenocarcinoma (OSA) and analyze the factors affecting prognosis. To detect the expressions of ERK1/2/MAPK signaling transduction associated protein and P53 in OSA and ovarian borderline serous tumor (OBST) and analyze relationship between expressions and clinicopathological paraeters. To discuss the relationship between ERK1/2/MAPK signaling transduction associated protein and P53 in OSA, and research their role in pathogenesis and development of OSA.Methods:A total of 95 cases of OSA from 1998 to 2010 treated in Nanjing General Hospital of Nanjing Military Command were reviewed retrospectively,38 cases OBST which include 11 cases from 2007 to 2010 treated in Nanjing General Hospital of Nanjing Military Command and 27 cases from 2005 to 2012 treated in Nanjing Maternity and Child Health Hospital as control. Expressions of p-ERK1/2, c-Myc, CIP2A and P53 were detected by immunohistochemistry technology in 17 cases of low-grade OSA and 78 cases of high-grade OSA, as well as the relationship among the expression level of p-ERK1/2, c-Myc, CIP2A, P53 and their correlation with degree of malignancy of OSA. Follow-up data was obtained from patient’s clinical database.The results were statistically processed and analyzed.Results:Histopathologically, low grade OSA is well differentiated papillary or adenoid structure with mild to moderate nuclear atypia. The mitotic rate is equal to or less than 12 per 10 high power fields, no necrosis and multinucleated giant cells was founded. High grade OSA was papillary, adenoid, screen hole or solid structure with marked nuclear atypia, more than 12 mitoses per 10 high power fields, OBST epithelial hyperplasia was stratified, plexiform, cribriform and micropapillary with light to moderate atypia,fewer mitotics,and often lacks destructive infiltrative growth.Immunohistochemically, ERK1/2/MAPK signaling transduction associated protein p-ERK1/2, c-Myc, CIP2A and P53 were overexpressed in OSA tissues. The expression of p-ERK1/2, c-Myc, CIP2A and P53 in OSA were significantly higher than OBST (P<0.05). p-ERK1/2 showed that positive signals were located in the nuclei and cytoplasm of tumor cells and the positive rate was 71.6%. The expressions of p-ERK1/2 were associated with clinical stages, tumor’s recurrence and the differences were significant (P< 0.05). The positive signals of c-Myc were located in the nuclei, a small part in cytoplasm. The positive rate was 76.8% in OSA. The expressions of c-Myc were associated with pathological grading, tumor maximum diameter and the differences was significant(P<0.05). The positive signals of CIP2A were located in the cytoplasm and the positive rate was 76.8%, its expression was associated with metastatic regional lymph nodes, clinical stages, pathological grading, tumor’s recurrence and the differences was significant(P<0.05). The positive signals of P53 were located in the nuclei. The positive rate was 68.4%, and its expression was associated with age, metastatic regional lymph nodes, pathological grading, tumor’s recurrence and the differences was significant (P<0.05)Correlation analysis:Spearman analysis showed that the expression of p-ERK1/2, c-Myc, CIP2A correlated positively with each other and the differences were significant. The expression of p-ERK1/2 in OSA was positively related to c-Myc(r= 0.343, P=0.001).The expression of c-Myc in OSA was positively related to CIP2A(r =0.651, P=0.000).The expression of CIP2A in OSA was positively related to p-ERK1/2 (i=0.412,P=0.000).Univariate survival analysis:Kaplan-Meier analysis demonstated that clinical grade, recurrence, pathological grading, metastatic regional lymph nodes, tumor’s location, and the expressions of CIP2A and P53 were all related to the prognosis (P< 0.05), however, age and tumor maximum diameter are not related to prognosis. Cox regression showed that recurrence and clinical stages were the independent factor to affect prognostic in OSA.Conclusion:Expression of CIP2A and P53 are closely related to the degree of malignancy, invasiveness and metastasis of OSA, and act as a marker to predict the tumor recurrence and poor prognosis. Although CIP2A and P53 immunostaining was valuable in assisting pathological grading, it should be cautious to use it alone as an independent indicator in predicting the prognosis of OSA.p-ERK1/2 and c-Myc are not better than CIP2A in predicting the degree of malignancy and prognosis in OSA,but may play an important role in the development of OSA.p-ERK1/2, c-Myc, CIP2A were overexpressed in OSA tissues. The expression of p-ERK1/2, c-Myc, CIP2A correlated positively with each other and the differences was significant. These indicate that ERK1/2/MAPK signaling transduction associated protein may have synergistic effect in the occurrence and development of OSA, and play an important role in maintaining malignant phenotype.ERK1/2/MAPK signaling transduction pathway and P53 pathway is not opposition to each other in developing process of OSA. There are connections between pathways, interactions of the important factors influence the occurrence and development of OSA.