Diagnostic Validity of Serum and Peritoneal TNF-alpha , High Sensitivity CRP and Plasma Cell-Free Nuclear DNA ( ccf nDNA ) as Biomarkers of Pelvic Endometriosis : A Case Control Study

Introduction:Endometriosis is a disease defined by the presence of endometrial glands and stroma located outside the uterine cavity. These ectopic implants can be found throughout the pelvis, on and within the ovaries, abutting the uterine ligaments, occupying the rectovaginal septum, invading the intestinal serosa, and along the parietal peritoneum. Endometrial implantation at distant sites such as the pleura, lung, within surgical scars, and along the diaphragm also has been reported. (1).  It results often in subfertility and pain, occurs mainly in women of reproductive age (16–50 years) and has a progressive character in at least 50%, but the rate and risk factors for progression are unknown. Endometriosis can be classified into four stages: minimal, mild, moderate and severe. The gold standard for the diagnosis of endometriosis is laparoscopic inspection, ideally with histological confirmation. (2), however, is an invasive technique and should be performed only after imaging techniques prove insufficient for confident diagnosis. (3) Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis. (2) Additional tools are needed for non-invasive classifications in order to reduce the number of unnecessary laparoscopies without adversely affecting outcomes. Finding specific and   more sensitive biomarkers in endometriosis is critical, because endometriosis is usually diagnosed only in advanced stages, and there is a high rate of morbidity for this disease. (4)   Aim of the work: The aim of the current study is to assess the validity of serum and peritoneal high sensitivity CRP and TNF-alpha and plasma cell-free nuclear DNA (ccf nDNA) as biomarkers in early diagnosis of pelvic endometriosis. Methods: This study was conducted at the Obstetrics & Gynecology department, Maternity Hospital, Ain Shams University. This is a case control study of 120 women scheduled for diagnostic laparoscopy. Laparoscopy was indicated in these women whether for various causes of subfertility or for chronic pelvic pain between January 2011 and January 2012. The patients were divided into the following groups: Group I (endometriosis group/ study group) consisted of 80 patients diagnosed to have endometriosis during laparoscopy. Group I cases were subdivided into two subgroups, Group IA: consisted of 34 cases with stage 1or minimal endometriosis and Group IB: consisted of 46 cases with stage 2 or mild endometriosis. Group II (non-endometriosis group/Control group): consisted of 40 cases with no detected pelvic pathology. During the laparoscopy procedure, both peripheral venous blood and peritoneal samples were withdrawn. Serum and peritoneal levels of high sensitivity CRP and TNF-alpha as well as plasma levels of ccf nDNA were compared in both groups and in early stages (minimal and mild) of endometriosis within the study group. Results: Serum TNF-a, serum hs-CRP and plasma ccf DNA were significantly elevated in cases compared with the control group. They were also elevated in patients with group IA and group IB as compared to control group. However, there was no statistically significant difference between cases and control group as regards peritoneal TNF-a and peritoneal hs-CRP. There was no significant difference between the group IA and group IB as regards all biomarkers. Conclusion: Our results showed that serum TNF-alpha , serum hs-CRP and plasma ccf DNA are highly reliable biomarkers for screening and early diagnosis of endometriosis,  but they  can not be used to discriminate between stage I and stage II. On the other hand, peritoneal TNF-a and peritoneal hs-CRP are non reliable for early diagnosis of endometriosis and can not be used to discriminate between stage I and stage II of endometriosis.