Tumor Markers in Endometriosis

Extensive research has been dedicated to the diagnosis and treatment of endometriosis over the years. Like in many other medical fields, scientists work diligently to develop efficient, straightforward, and cost-effective diagnostic methods. Given that various biomarkers are already being used to diagnose numerous other diseases, it is reasonable to explore their potential application in diagnosing endometriosis. Numerous studies, which are referenced below, have delved into this subject, yielding varying outcomes.

In a 1999 study, researchers assessed the presence and concentration of several tumor markers in individuals with pelvic endometriosis lesions. The features included CA-125, CA-15-3, CA-19-9, CEA (carcinoembryonic antigen), AFP (alpha-fetoprotein), and B2MG (beta-2 microglobulin). The study involved 50 participants, divided into two groups: a control group of healthy individuals and a group of 35 endometriosis patients. Blood samples were collected from all participants, once during menstruation and again one week later. The result revealed that only CA-125 levels were elevated in individuals with stage 3 to 4 endometriosis, while all other markers remained within normal ranges for all 50 participants. The blood samples taken during menstruation were particularly informative [5]. It is worth mentioning that CA-125 levels can also increase slightly during ovulation and more significantly during menstruation, which is considered a normal physiological response [6].

A similar study was conducted in 1997, examining CA-125 levels and other biomarkers, including CRP (C-reactive protein). CRP is exciting as it is an inflammation marker in the blood. This study arrived at the same conclusion as the previous [7].

Both studies provided valuable insights, suggesting that the tumor marker CA-125 could be a potential diagnostic tool for endometriosis, though the studies primarily focused on pelvic endometriosis. Additionally, the sample size in these studies was relatively small, which initially limited their significance. Subsequent studies have further explored this topic.

In 2001, researchers investigated whether elevated CA-125 levels could also be detected in the peritoneal fluid within the abdomen. Previous studies had only analyzed blood samples for this marker without considering other bodily fluids. In previous studies, earlier stages could not be identified using this method because elevated CA-125 levels were only found in stage 3 or higher endometriosis. This study aimed to determine if peritoneal fluid could be used to diagnose early-stage endometriosis. It involved examining 107 individuals, both with and without endometriosis, through abdominal endoscopy during the menstrual cycle’s luteal or corpus luteum phase (from ovulation to the start of menstrual bleeding). The result showed that compared to the healthy control group, individuals with endometriosis had significantly higher CA-125 levels in their peritoneal fluid. Notably, this increase was observed even in early stages 1 and 2 of the condition. [8].

Detecting endometriosis foci during laparoscopy can be challenging, as the lesions are often concealed and relatively small, requiring a trained eye. The findings from this study suggested that diagnosis could be simplified in the future. For instance, peritoneal fluid could be collected during the laparoscopy and tested for CA-125, potentially enabling diagnosis even when endometriosis lesions are not readily visible.

2015, a comprehensive meta-analysis spanning the years 2000 to 2014 was conducted. The meta-analysis assessed studies investigating tumor markers CA-125, CA-19-9, and CA-15-3 in relation to endometriosis. CA-19-9 is elevated in multiple tumor diseases, particularly pancreatic, gastric, and ovarian carcinoma [9]. CA-15-3 is typically elevated in breast cancer [10]. The meta-analysis encompassed 12 studies involving over 1,000 participants, all of whom had their blood samples analyzed for tumor markers. The results confirmed the findings from earlier studies: CA-125 levels were significantly elevated in many individuals with endometriosis, regardless of whether it was in the early or late stages. CA-19-9 was also associated with endometriosis, but its elevation was more prominent in stages 3 and 4, with no significant changes observed in earlier stages. Conversely, CA-15-3 did not appear to hold diagnostic significance for endometriosis. While some studies reported elevated levels in later stages for specific individuals, these isolated cases did not contribute significantly to their diagnostic value [11].

It appears evident that the tumor marker CA-125 can indeed be valuable for diagnosing endometriosis. However, a persistent challenge is determining the threshold value that qualifies as diagnostic and how to define an elevated value. Various studies suggested different thresholds for diagnostic relevance. For instance, some studies proposed that a value exceeding 30 U/ml (units per milliliter) is diagnostically significant. While other studies have corroborated this threshold, it is essential to note that a value below 30 U/ml does not necessarily rule out the presence of endometriosis. Moreover, certain studies made distinctions based on the menopausal status of individuals. In individuals who are still menstruating, a diagnostic value above 37 U/ml has been suggested, whereas postmenopausal individuals may have a diagnostic threshold of above 35 U/ml [12].