Exploring Tumor Markers in Endometriosis Diagnosis

The quest for efficient, uncomplicated, and cost-effective methods of diagnosing endometriosis has been a long-standing endeavor in medicine. Given the success of various biomarkers in diagnosing other diseases, their potential application in endometriosis diagnosis is a logical area of exploration. Numerous studies have tackled this subject, yielding diverse findings.

One study in 1999 delved into the presence and concentration of multiple tumor markers in individuals with pelvic endometriosis lesions. The markers CA-125, CA-15-3, CA-19-9, CEA (carcinoembryonic antigen), AFP (alpha-fetoprotein), and B2MG (beta-2 microglobulin) were tested in 50 participants, categorized into two groups: healthy individuals (control group) and 35 endometriosis patients. Blood samples were collected during menstruation and one week later. The study revealed that only CA-125 exhibited elevated levels in individuals with stage 3 to 4 endometriosis, while other markers remained unremarkable across all 50 participants. Interestingly, blood samples taken during menstruation provided particularly informative data. It is noteworthy that CA-125 levels undergo slight increases during ovulation and slightly more during menstruation, which are normal fluctuations and not cause for concern [5].

A similar study conducted in 1997 extended the investigation to include the biomarker CRP (C-reactive protein) and CA-125, among others. CRP is of particular interest as an inflammation marker in the blood. This study corroborated the findings of the previous one, emphasizing CA-125’s potential significance in diagnosing endometriosis [7].

Both studies thus provided essential insights into the fact that the tumor marker CA-125 could be of interest for diagnosing endometriosis. However, only patients with endometriosis in the pelvic region were involved. However, it is essential to recognize that both studies primarily involved patients with pelvic endometriosis, and the sample size was relatively small, initially limiting their significance. Subsequent studies further explored this avenue.

In 2001, a study sought to determine whether elevated CA-125 levels could also be detected in peritoneal fluid within the abdominal cavity, expanding beyond the scope of previous studies that focused solely on blood samples. This study explored the potential of peritoneal fluid analysis for diagnosing endometriosis, particularly in its early stages. The investigation involved 107 participants, both with and without endometriosis, who underwent abdominal endoscopy during the menstrual cycle’s luteal or corpus luteum phase, spanning from ovulation to the onset of menstrual bleeding. The results were intriguing. Individuals with endometriosis exhibited elevated CA-125 levels in their peritoneal fluid, a finding that was consistent with expectations. However, this discovery was particularly noteworthy because of the significantly higher CA-125 levels in peritoneal fluid compared to blood samples and the early-stage elevation observed in stages 1 and 2 of endometriosis [8].

The study’s implications are promising, potentially simplifying the diagnostic process for endometriosis, especially in cases where endometriosis foci are challenging to detect during laparoscopy due to their concealed or petite nature. In the future, this research suggests that peritoneal fluid analysis and CA-125 testing could facilitate diagnosis even when visible endometriosis foci are absent.

2015, a comprehensive meta-analysis revisited the topic, reviewing studies conducted between 2000 and 2014. These studies focused on tumor markers CA-125, CA-19-9, and CA-15-3. CA-19-9 is typically elevated in various tumor diseases, including pancreatic, gastric, and ovarian cancers [9], while CA-15-3 is associated with breast cancer [10]. The meta-analysis evaluated 12 studies involving more than 1,000 individuals in which blood samples were analyzed for tumor markers. The meta-analysis encompassed 12 studies involving over 1,000 participants undergoing blood tests for tumor markers. The results corroborated earlier findings: CA-125 was significantly elevated in individuals with endometriosis, spanning the early and late stages of the disease. CA-19-9 also displayed associations with endometriosis, predominantly in late stages 3 and 4, with no significant changes in earlier stages. However, CA-15-3 did not appear to hold diagnostic relevance for endometriosis, with occasional elevation in later stages but without sufficient significance [11].

While the utility of CA-125 as a diagnostic tool for endometriosis appears promising, challenges remain regarding the precise threshold for diagnosis. Some studies suggest a diagnostic value above 30 U/ml (units per milliliter). However, it is crucial to recognize that a value below 30 U/ml does not rule out the presence of endometriosis. Moreover, distinctions between pre- and post-menopausal individuals have been noted, with a diagnostic value exceeding 37 U/ml for menstruating individuals and 35 U/ml for post-menopausal individuals. Further research is warranted to refine diagnostic criteria and better harness the potential of tumor markers in endometriosis diagnosis [12].