Expression And Significance Of SRSF2?HMGA2?E2F1 And Caspase-3 In Ovarian High Grade Serous Carcinoma And Precursor Lesions

ObjectiveOvarian cancer is a gynecological malignant tumor with the highest mortality rate in female,the patients died of High-grade serous ovarian cancer(HGSOC)account for 70-80% of those who died of ovarian cancer.Women with HGSOC had a poor clinical outcome due to the advanced stage(stage ?)in the initial diagnosis?recurrence?metastasis and the emergence of drug-resistance.The aberrant apoptosis is one of the most important reasons of drug-resistance in tumor.Abnormal expressions of SRSF2?HMGA2 and E2F1 leads to irregular apoptosis of HGSOC While the relationships between them is not clear.The research mainly studied the expression of SRSF2?HMGA2?E2F1 and Caspase-3 in HGSOC and precursor lesions,Relations between the four markers as well as relationship between them and several clinical pathological parameters were analyzed.The study made a preliminary discussion about the possible mechanisms of regulation of apoptosis involving SRSF2?HMGA2?E2F1 and Caspase-3 in HGSOC and the clinical value they may have.Methods136 cases of high-grade serous ovarian/ fallopian tube carcinoma and precursor lesions were collected from the department of pathology,Tianjin Medical University General Hospital from January 2013 to may 2018.All the cases were reviewed in accordance with the diagnostic criteria of WHO classification of Female Reproductive Organ Tumors(4th edition,2014).And they were divided into 5 groups:HGSOC,Fallopian tube high grade serous carcinoma,serous fallopian tube intraepithelial neoplasia(STIC),P53 signature and SCOUT.Immunohistochemical method was used to detect the expression of SRSF2?HMGA2?E2F1 and Caspase-3,and statistical analysis was performed using SPSS17.0 statistical software.Results1.The expression of SRSF2?HMGA2?E2F1 and Caspase-3 in the five groupsThe positive expressions of both SRSF2 and Caspase-3 showed a decreasing tendency in SCOUT?P53 signature?STIC?Fallopian tube high grade serous carcinoma and HGSOC,while HMGA2 and E2F1 showed an increasing tendency(P<0.05).The positive expression of SRSF2 in SCOUT?P53 signature?STIC?Fallopian tube high grade serous carcinoma and HGSOC was 80%?76.9%?33.3%?35.1% and 37.5% respectively,Which of HMGA2 was 20%?30.8%?55.6%?73.0% and 79.2% respectively,which of E2F1 was 25.0%?30.8%?66.7%?59.5% and 56.3% respectively,Which of Caspase-3 was 85.0%?76.9%?38.9%?48.7% and 45.8% respectively.There were no significant differences in the expression of SRSF2,HMGA2,E2F1 and Caspase-3 among STIC,Fallopian tube high grade serous carcinoma and HGSOC(P>0.05).There were significant differences in the expression of SRSF2,HMGA2,E2F1 and Caspase-3 between STIC and SCOUT(P<0.05).There were significant differences in the expression of SRSF2 and Caspase-3 in STIC and P53 signature(P<0.05).2.The correlation of the expression of SRSF2?HMGA2?E2F1 and Caspase-3In HGSOC and precursor lesions,positive correlations between the expression of SRSF2 and Caspase-3?HMGA2 and E2F1(r values 0.622 and 0.383 respectively,P<0.05)could be obtained,negative correlations between the expression of HMGA2 and Caspase-3?E2F1 and Caspase-3 ?SRSF2 and HMGA2 could be obtained(r values-0.373?-0.396 and-0.329 respectively,P<0.05).3.The relationships between the Clinical pathological parameters and the expressions of the four markers including SRSF2?HMGA2?E2F1 and Caspase-3There were no correlations between the expressions of the four markers and clinical pathological parameters including FIGO stage?tumor size and patient age(p>0.05).Conclusions1.SRSF2 ?HMGA2 ?E2F1 and Caspase-3 may involved in the initiation and progression of HGSOC.They may regulate apoptosis synergistically in HGSOC.2.The expressions of SRSF2?HMGA2?E2F1 and Caspase-3 in Fallopian tube/ Ovarian high grade serous carcinoma may not be related with FIGO stage?tumor size and patient age.