1.A Study On The Relationships Among Heat Shock Protein, P53 Protein And The Prognosis Of Advanced Ovarian Serous Adenocarcinoma 2.Predictive Value Of CT And CA125 In The Outcome Of PrimaryCytoreductive Surgery For Advanced Serous Ovarian Cancer

Part 1A Study on the Correlation Between the Expression of Heat shock proteins and the Prognosis of Advanced Ovarian Serous AdenocarcinomaBackground:Heat shock protein family plays an important role in the occurrence and development of malignant tumors. HSPs are overexpressed in many malignant tumors, which plays an important role in the formation, development, drug resistance and prognosis of tumors.Objective:To screen the prognosis-related protein expression of ovarian serous cancer. To estimate the expression in advanced ovarian serous adenocarcinoma (AOSC) tissue specimens, and to assess its association with clinicopathological features and survival of AOSC patients.Methods:From Previous mass spectrometry study we obtain the Ovarian cancer secreted/ released protein database.7 proteins related to cancer resistance and prognosis from the database was selected.218 patients who accept the primary cytoreductive surgery from January 2003 to December 2013 was in enrolled in this study.Tissue samples from 9 patients were collected for Western Blot,in order to detect the candidate difference expressed proteins. Paraffin-embedded tissues from 202 patients were collected for making tissue microarray. Immunohistochemical analysis was perform for the candidate proteins expression.Results:HSP90AB1 and TRAP1 were determined as the candidate difference proteins. HSP90AB1 high expression rate of 59.9%(121/202); TRAP1 expression was 36.6% (74/202). Chi-square test showed that there is no significant correlation between HSP90AB1 expression and clinicopathological factors. TRAP1 expression is correlated with platinum-resistance and Preoperative CA125 levels (P = 0.05,0.034), and no significant correlation with other clinicopathological factors. Univariate analysis showed that the high HSP90AB1 expression group of patients had relative poor prognosis:overall survival OS、progression-free survival PFS and treatment-free interval TFI were significantly shorter; (P = 0.003,0.029,0.032); the high TRAP1expression group of patients had relative good prognosis:overall survival OS、progression-free survival PFS treatment-free interval TFI were significantly prolonged; (P<0.001,= 0.03,= 0.035).Multivariate analysis showed that overall survival of HSP90AB1 high expression group was significantly shortened P = 0.044 (HR1.573 95% CI 1.013-2.443,); overall survival of TRAP1 high expression group was significantly prolonged, P<0.001 (HR 0.427 95% CI 0.269-0.678), In both univariate and multivariate analysis, OS、PFS、TFI were significantly shorten in Platinum Resistance group P<0.001.Conclusion:HSP90AB1, TRAP1 expression are significant correlated with the prognosis of advanced OSC patients, HSP90AB1 expression level was negatively correlated with prognosis, and TRAP1 expression level was negatively correlated with prognosis, which can be used as an important predictor of AOSC prognosis. Platinum Resistance was significant correlated with poor prognosis.Part 2A Study on the Relationship Between the Expression of p53 Protein and the Prognosis of Advanced Ovarian Serous AdenocarcinomaBackground:Difficult early diagnosis, drug resistance, lack of effective prognostic indicators are important reasons for the poor prognosis of ovarian cancer. Looking for new diagnostic markers, understanding the occurrence and development of ovarian cancer are important means to improve the prognosis. P53 is one of the earliest discovered tumor suppressor genes. P53 mutation is an important link in the development of a variety of malignant tumors. The mutant P53 has been proved to have a close correlation with the poor prognosis of many kinds of malignant tumors. The relationship between prognosis and tumor specific protein markers is of great significance in ovarian cancer.Objective:To study the expression of p53 protein in advanced ovarian serous adenocarcinoma and to explore the correlations to the clinicopathological features and prognosis.Methods:The immunohistochemical staining was used to detect the expression of p53 protein in 183 patients with advanced ovarian serous carcinoma. The correlation of p53 protein to the clinicopathological features and its significance in the assessment of prognosis were explored.Results:The p53 protein expression was positive in 62.8% of the patients. Chi-square test showed that the overexpression of p53 protein was positively correlated with the elevation of serum CA125 and the Two-Tier grading of ovarian serous adenocarcinoma(P < 0.001, P=0.038). Univariate analysis suggested that the prognosis of patients was associated with Two-Tier grading, lymph node metastasis, preoperative serum CA125 level and p53 overexpression (P = 0.007,0.036,0.002,<0.001). Multivariate analysis showed that FIGO stage, lymph node metastasis and overexpression of p53 were independent prognostic factors (P=0.038,0.002,0.001)Conclusion:The expression of p53 protein is closely related to the prognosis of advanced ovarian serous carcinoma, and can be used as an important indicator for predicting the prognosis.Part 3Preoperative Computed Tomography and Serum CA-125 to predict the outcome of primary cytoreductive surgery for advanced serous ovarian cancerBackground:CA125 is a commonly used tumor marker for ovarian cancer, and computed tomography (CT) is a common imaging tool for the diagnosis and clinical evaluation of ovarian cancer. Residual tumor after surgery is an important factor affecting the prognosis of ovarian cancer. The non-invasive imaging examination and serological examination as the evaluation methods for predicting optimal cytoreductive surgery of ovarian cancer is a hot research topic.Objective:To estimate the value of preoperative computed tomography (CT) scan and serum CA-125 in predicting optimal cytoreductive surgery in advanced ovarian serous cancer.Methods:From January 2003 to November 2014, patients histologic diagnosed of stage III-IV ovarian serous carcinoma enrolled in this retrospective study, underwent primary cytoreductive surgery in cancer hospital chinese academy medical science Department of Gynecologic Oncology. Abdomen/pelvis CT scans and CA-125 were obtained 2 weeks before primary surgery, all CT imagings were retrospectively analyzed by 15 radiologic criteria which were blinded to the surgery findings.5 clinical criteria from medical record were also accessed.Results:282 patients were enrolled in this study; optimal cytoreduction was achieved in 73%. The overall sensitivity of CT in predicting suboptimal primary Cytoreduction was 91%, the specificity was 84% and the positive predictive value was 69% and the negative predictive value was 96%. On multivariate analysis, six radiologic criteria were significantly associated with suboptimal primary Cytoreductive surgery:suprarenal retroperitoneal lymph nodes>1cm (P<0.001), Perihepatic lesion or liver metastases>2cm (P=0.006), colon and mesocolon invasion>2cm (P=0.006), lesser sac and transverse mesocolon invasion>2cm (P<0.001), gastrosplenic ligament invasion>2cm (p<0.001), sigmoid colon and rectum invasion>2cm(P<0.001). CA-125 levels fail to predict the optimal cytoreduction (P=0.386).Conclusion:Our study indicated that preoperative CT predicting primary optimal cytoreduction is feasible, identified six criteria correlated to suboptimal cytoreduction, which probably helpful in primary treatment assessment, CA-125 level> 500 U/mL was not associated with suboptimal cytoreduction.