Evaluation of biomarkers in the detection of malignant neoplasia in women with adnexal mass

• Grant number: 12/24143-2
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2013
• Effective date (End): February 28, 2014
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Sophie Françoise Mauricette Derchain
• Grantee: Heloisa Takasu Peres
• Home Institution: Centro de Atenção Integral à Saúde da Mulher (CAISM). Hospital da Mulher Professor Doutor José Aristodemo Pinotti. Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

This project pertains to a line of research on potential clinical, sonographic and biochemical predictors of malignancy in women adnexal tumors. The objective of the study is to evaluate the accuracy of CA125, HE4 and mesotelin, standing alone or combined with sonographic findings and symptoms to differentiate ovarian tumors in women who underwent a laparotomy due to an adnexal mass. Subjects and methods: this diagnostic validation study is going to include women who attended consultations at the pelvic oncology - ovary clinics and who are scheduled to undergo a laparoscopy/laparotomy due to an adnexal mass in the Women's Hospital of the Campinas State University (CAISM-Unicamp). The patients group comprises women aged 18 years of above, with an adnexal tumor and an indication to undergo surgery, to be performed in CAISM, and the control group consists of clinically healthy women with normal pelvic exam and ultrasound. Women undergoing treatments for cancer, those who had undergone an oophorectomy and/or pregnant are excluded. After signing the informed consent form, 312 women with ovarian tumors and 152 controls were already included. The sample size was calculated on the basis of the sensitivity of CA125 and HE4 derived from previous studies, with 5% significance levels, 80% statistical power and 12% error limits for the sensitivity, according to the calculations proposed by Flahaul: the minimal size would be n=93(malignant), and based on the prevalence of malignancy, n=149 benignant tumors. The number of controls was estimated at n=149, totaling n=391. We started accrual in 2010 and after enrolling, all women responded to a structured interview concerning 24 symptoms related to ovarian cancer over the 12 months before the consultation. All patients will undergo transvaginal sonography (associated or not with abdominal sonography) for the evaluation of the tumor characteristics, which are going to be classified following strict criteria. Women with an indication for surgery for the diagnosis and/or treatment will be operated in CAISM. Peripheral blood samples will be collected from patients and controls. The 10mL samples are going to be stored in dry tubes and immediately frozen. The blood samples are then going to be left to rest for 30 minutes, allowing clot formation and next will be centrifuged in 1200g for 10 minutes. The total volume of serum thereby obtained will separated into 300µl aliquots and stored in -80ºC for future biomarker detection and quantification. Manuscripts derived from the present line of research have already been prepared: the first one (in press) addresses the sonographic findings (Hartman CA, Juliato CR, Sarian LO, Toledo MC, Jales RM, Morais SS, Pitta DD, Marussi EF, Derchain S. Ultrasound criteria and CA-125 as predictive variables of ovarian cancer in women with adnexal tumors. Ultrasound Obstet Gynecol. 2012 May 30. doi: 10.1002/uog.11201). The second has been submitted in the American Journal of Obstetrics and Gynecology (Barreta A, Bastos J, Sarian L, Toledo MC, Hartman C, Sallum LF, Pitta D, Derchain S. Laparotomy and Laparoscopy for Diagnosis and Treatment of Adnexal Masses at a Brazilian Oncology Center and Factors That Led to Laparoscopy Failure). With the analysis of the tumor markers, we expect to fulfill the main objective of the study, which is to assess the sonographic features, symptoms and biological markers, standing alone or in multiple combinations, as tools for the differentiation of adnexal masses. We started collecting data in 2010, and the collection is still in progress.