CA 125 also known as mucin 16 or MUC16 is a large membrane glycoprotein belonging to the wide mucin family, encoded by the homonymous MUC16 gene. Following its discovery in the blood of some patients ...with specific types of cancers or other benign conditions, CA125 has found application as a tumor marker of ovarian cancer. Thirty years after its discovery, use of CA 125 is still FDA-recommended to monitor response to therapy in patients with epithelial ovarian cancer and to detect residual or recurrent disease in patients who have undergone first-line therapy and would be considered for second-look procedures. However, due to its limited specificity and sensitivity, CA 125 alone cannot still be an ideal biomarker. Increased clinical performance, in terms of better sensitivity and specificity in identifying epithelial ovarian cancer relapse, has been obtained by combined use of CA 125 with HE4, another ovarian cancer marker recently introduced in clinical use. Significant advancements have been achieved more recently, due to the introduction of FDA-approved ROMA and OVA1 algorithms to evaluate the risk of ovarian cancer for patients with a pelvic mass.
Background
About 10% of reproductive‐aged women suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for ...endometriosis, but is expensive and carries surgical risks. Currently, there are no non‐invasive or minimally invasive tests available in clinical practice to accurately diagnose endometriosis. Although other reviews have assessed the ability of blood tests to diagnose endometriosis, this is the first review to use Cochrane methods, providing an update on the rapidly expanding literature in this field.
Objectives
To evaluate blood biomarkers as replacement tests for diagnostic surgery and as triage tests to inform decisions on surgery for endometriosis. Specific objectives include:
1. To provide summary estimates of the diagnostic accuracy of blood biomarkers for the diagnosis of peritoneal, ovarian and deep infiltrating pelvic endometriosis, compared to surgical diagnosis as a reference standard.
2. To assess the diagnostic utility of biomarkers that could differentiate ovarian endometrioma from other ovarian masses.
Search methods
We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as these databases to 20 April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed.
Selection criteria
We considered published, peer‐reviewed, randomised controlled or cross‐sectional studies of any size, including prospectively collected samples from any population of reproductive‐aged women suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of one or more blood biomarkers with the findings of surgical visualisation of endometriotic lesions.
Data collection and analysis
Two authors independently collected and performed a quality assessment of data from each study. For each diagnostic test, we classified the data as positive or negative for the surgical detection of endometriosis, and we calculated sensitivity and specificity estimates. We used the bivariate model to obtain pooled estimates of sensitivity and specificity whenever sufficient datasets were available. The predetermined criteria for a clinically useful blood test to replace diagnostic surgery were a sensitivity of 0.94 and a specificity of 0.79 to detect endometriosis. We set the criteria for triage tests at a sensitivity of ≥ 0.95 and a specificity of ≥ 0.50, which 'rules out' the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of ≥ 0.50 and a specificity of ≥ 0.95, which 'rules in' the diagnosis with high accuracy if there is a positive result (SpIN test).
Main results
We included 141 studies that involved 15,141 participants and evaluated 122 blood biomarkers. All the studies were of poor methodological quality. Studies evaluated the blood biomarkers either in a specific phase of the menstrual cycle or irrespective of the cycle phase, and they tested for them in serum, plasma or whole blood. Included women were a selected population with a high frequency of endometriosis (10% to 85%), in which surgery was indicated for endometriosis, infertility work‐up or ovarian mass. Seventy studies evaluated the diagnostic performance of 47 blood biomarkers for endometriosis (44 single‐marker tests and 30 combined tests of two to six blood biomarkers). These were angiogenesis/growth factors, apoptosis markers, cell adhesion molecules, high‐throughput markers, hormonal markers, immune system/inflammatory markers, oxidative stress markers, microRNAs, tumour markers and other proteins. Most of these biomarkers were assessed in small individual studies, often using different cut‐off thresholds, and we could only perform meta‐analyses on the data sets for anti‐endometrial antibodies, interleukin‐6 (IL‐6), cancer antigen‐19.9 (CA‐19.9) and CA‐125. Diagnostic estimates varied significantly between studies for each of these biomarkers, and CA‐125 was the only marker with sufficient data to reliably assess sources of heterogeneity.
The mean sensitivities and specificities of anti‐endometrial antibodies (4 studies, 759 women) were 0.81 (95% confidence interval (CI) 0.76 to 0.87) and 0.75 (95% CI 0.46 to 1.00). For IL‐6, with a cut‐off value of > 1.90 to 2.00 pg/ml (3 studies, 309 women), sensitivity was 0.63 (95% CI 0.52 to 0.75) and specificity was 0.69 (95% CI 0.57 to 0.82). For CA‐19.9, with a cut‐off value of > 37.0 IU/ml (3 studies, 330 women), sensitivity was 0.36 (95% CI 0.26 to 0.45) and specificity was 0.87 (95% CI 0.75 to 0.99).
Studies assessed CA‐125 at different thresholds, demonstrating the following mean sensitivities and specificities: for cut‐off > 10.0 to 14.7 U/ml: 0.70 (95% CI 0.63 to 0.77) and 0.64 (95% CI 0.47 to 0.82); for cut‐off > 16.0 to 17.6 U/ml: 0.56 (95% CI 0.24, 0.88) and 0.91 (95% CI 0.75, 1.00); for cut‐off > 20.0 U/ml: 0.67 (95% CI 0.50 to 0.85) and 0.69 (95% CI 0.58 to 0.80); for cut‐off > 25.0 to 26.0 U/ml: 0.73 (95% CI 0.67 to 0.79) and 0.70 (95% CI 0.63 to 0.77); for cut‐off > 30.0 to 33.0 U/ml: 0.62 (95% CI 0.45 to 0.79) and 0.76 (95% CI 0.53 to 1.00); and for cut‐off > 35.0 to 36.0 U/ml: 0.40 (95% CI 0.32 to 0.49) and 0.91 (95% CI 0.88 to 0.94).
We could not statistically evaluate other biomarkers meaningfully, including biomarkers that were assessed for their ability to differentiate endometrioma from other benign ovarian cysts.
Eighty‐two studies evaluated 97 biomarkers that did not differentiate women with endometriosis from disease‐free controls. Of these, 22 biomarkers demonstrated conflicting results, with some studies showing differential expression and others no evidence of a difference between the endometriosis and control groups.
Authors' conclusions
Of the biomarkers that were subjected to meta‐analysis, none consistently met the criteria for a replacement or triage diagnostic test. A subset of blood biomarkers could prove useful either for detecting pelvic endometriosis or for differentiating ovarian endometrioma from other benign ovarian masses, but there was insufficient evidence to draw meaningful conclusions. Overall, none of the biomarkers displayed enough accuracy to be used clinically outside a research setting. We also identified blood biomarkers that demonstrated no diagnostic value in endometriosis and recommend focusing research resources on evaluating other more clinically useful biomarkers.
La masa pélvica es un proceso frecuente en mujeres cuyas edades están comprendidas entre los 10 a 70 años. La mayoría, en sus inicios no se acompañan de síntomas, por lo que es el médico, a través de ...la sospecha el que tiene que ordenar los exámenes necesarios para la detección precoz y oportuna de la misma ha sabiendas de que confundido entre una masa pélvica puede estarse gestando un cáncer de ovario en estado incipiente. Establecida la masa los procedimientos mas utilizados para el estudio y diagnóstico de la misma son la ecografía simple y el eco doppler, la Tomografía abdominal y como marcadores el ca 125. La cirugía es el método tanto para el diagnóstico definitivo como para el tratamiento, haciendo hincapié en la importancia de la congelación para la resolución in situ del problema. Se analizan en el presente estudio 15 casos evaluados y tratados en el Servicio de Ginecología del Instituto Oncológico Nacional desde julio a diciembre del año 2004 y cuyas edades oscilan entre los 16 y 66 años con promedio 41 años. Los resultados fueron: 5 casos de endometriomas, 3 adeno-carcinomas de ovario, 3 patologías no ginecológicas y 4 patologías ginecológicas no tumorales. Se analizan además la relación con la imagenología, el ca 125, y los hallazgos patológicos definitivos.
To assess the role of fluid aspiration in ovarian preservation from a great anechoic cystic adnexal mass. In addition, the diagnostic value of fluid levels of estradiol and CA 125 were examined.
A ...prospective longitudinal study using clinical and ultrasound data collected for all patients under 19 years of age with clear cystic adnexal masses and ultrasonographic presence of the ipsilateral normal ovarian tissue, or the ovarian crescent sign (OCS) as a predictor of benign origin, with volume ≥200 ml, managed between January 2006 and November 2022. Aspiration was performed before surgery with the aim of strengthening the normal ovarian tissue to be whole preserved during laparoscopic stripping. In patients with suspicious for torsion samples was taken during laparoscopy.
Pediatric and Adolescent Gynecology Departments in hospitals in three European countries.
Surgical treated 92 patients with anechoic cystic adnexal masses.
Ovarian volume, the presence of OCS and anechoic content were reported. From first syringe, fluid level of estradiol in pg/l and CA 125 in IU/ml were measured and correlated with postoperative histologic findings.
The median cyst volume was 570 ml (range between 200 and 7600 ml). The normal ovarian tissue was reported, and no malignancy was found in all of 92 patients laparoscopically treated. Paraovarian cysts was considered on ultrasonography in 39 patients, but in four of them intrafilamentary ovarian cystadenomas was confirmed during laparoscopy. With laparoscopic stripping, the whole ovaries were preserved in nine patients with cystic mature teratomas and in 42 patients with serous cystadenomas including largest of 7600 ml. Torsion was reported in three of previous mentioned paraovarian cysts and in six ovarian cystic masses. Fluid levels of estradiol and CA 125 were successfully measured in all cystic masses except two ovarian torsions. CA 125 was significantly elevated in all serous cystadenomas and paraovarian cysts, Table 1, but estradiol was elevated only in four of functional ovarian cysts. In all large cystic mature teratomas both fluid markers remained low. Ovarian volume recovered to normal value within three months, as previous reported.
▪
Aspiration of cyst fluid before surgery in clearly defined patients may be very helpful to insuring ovarian tissue preservation in large cystic masses. Fluid levels of estradiol and CA 125 correlate with histology diagnosis and can be useful in distinguishing functional cysts from serous cystadenomas and paraovarian cyst, and cystic mature teratomas.
: Pathologies of adnexal masses are commonly benign. The malignant lesions of adnexa carries a very low five-year survival rate, and hence the early recognition need to be done. There is no single ...gold standard investigation for the diagnosis of the malignancy of the adnexa. Risk of Malignancy Index (RMI) scoring system, combines the Serum CA 125(U/ML), Ultrasound score (U) and the menopausal status(M).
: To assess the efficiency of Risk of Malignancy Index-3 (RMI-3) scoring system in discriminating benign and malignant adnexal mass, for early detection and management of malignant ovarian mass.
: This is a prospective, observational study, among 50 female patients above the age of 25 years, diagnosed with adnexal mass under the Department of obstetrics and gynaecology, Government Rajaji Hospital, affiliated to Madurai Medical College, Madurai.
All the study participants were subjected to detailed history taking, thorough clinical examination, ultrasonogram of abdomen and pelvis, and markers such as CA 125. Risk of Malignancy Index was calculated and correlated with the histopathological (HPE) findings of the excised tumours.
: When the cut off of RMI score for predicting malignancy is 149.2 which had a sensitivity of 79.2%, specificity of 92.3%, positive predictive value of 90.47%, negative predictive value of 82.78% and a diagnostic accuracy of 86.01%.
: Risk of Malignancy Index score is a simple tool, with a good diagnostic accuracy, hence it can be used as good screening tool for identification of the malignant lesions from the adnexal mass.
Ovarian cancer (OV) is the second most mortal gynecological malignancy. The oncomarker CA125 has been used as the main ovarian cancer marker for diagnosing and screening ovarian cancer in stages I ...and II. Therefore, sensitive and real-time detection of CA 125 is critical in ovarian cancer monitoring. Various tests are used to diagnose the CA 125. In recent years, modern methods such as biosensor technology have replaced the old tests for rapid, sensitive and specific detection of CA 125. Various types of biosensors are being developed, among which Surface Plasmon resonance (SPR) biosensors are one of the most important and remarkable types. Considering the importance of SPR biosensors in the diagnosis of enocomarker CA 125, the main focus of the present study is to consolidate the research work from the past two decade to the present. Also, the advantages and challenges in SPR biosensors development have been considered in the detection of CA 125 oncomarker.
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•Ovarian cancer (OC) is a group of maladies that originates in the ovaries, or the associated areas of the fallopian tubes and the peritoneum.•CA125 is a severely glycosylated type I transmembrane protein that is overexpressed in several tumors and pancreatic.•Several types of biosensors, have been developed in numerous fields, and medical sciences.
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