Tumor Markers in Endometriosis Diagnostics
As you may be aware, various techniques are employed in diagnosing endometriosis. Ultrasound typically provides an initial assessment, while laparoscopy is the gold standard. Ideally, a quick and straightforward blood test could detect endometriosis. Many diseases already benefit from such diagnostic methods, utilizing markers like tumor markers in cancer diagnosis. This article delves into the potential use of these markers in endometriosis diagnostics.
What are Tumor Markers?
Tumor markers are biological substances produced either by a tumor or as a body’s response to cancer. They belong to a subgroup of biomarkers commonly employed in cancer diagnostics. These markers are detectable in blood or other bodily fluids, making them valuable tools for diagnosis.
Some tumor markers consistently fall within a normal range in the body, while others are specifically associated with cancer or other diseases. It is important to note that they are not standalone tests for cancer but rather support existing suspicions and indicate the potential organ affected by the tumor. Elevated values can also indicate non-tumor-related conditions, such as inflammation. For instance, the tumor marker PSA (prostate-specific antigen) can be found in healthy individuals, but its value should typically be below 4. Elevated values may suggest changes such as a prostate tumor. However, it is worth mentioning that this marker’s interpretation can be controversial, as a high value does not necessarily confirm prostate changes. In contrast, the protein AFP (alpha-fetoprotein) is typically produced only by fetuses in the womb, so its presence in adults or children often points to liver or testicular cancer.
However, the utility of tumor markers extends beyond diagnosis. They can be employed to assess the effectiveness of therapy. Make prognostic predictions about disease progression, determine cancer stage, and evaluate the possibility of recurrence, which involves the disease returning. For example, the presence of circulating tumor cells (CTCs) in the blood may predict a less favorable prognosis, as they can facilitate the formation of metastases – cancer cells located in other parts of the body, indicating cancer spread. In ovarian cancer, the CA-125 marker can be measured to assess therapy effectiveness [1],[2],[3].
Furthermore, tumor markers are gaining importance in the field of personalized medicine. Since tumors can exhibit diverse characteristics in different individuals, including varying growth rates and treatment responses, creating an individualized profile is crucial. Tumor markers play a role in tailoring effective treatment plans, ultimately enhancing treatment success and saving valuable time by avoiding ineffective treatment attempts that may allow the tumor to progress [4].
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].
Conclusion – Can Endometriosis Detection Benefit from Tumor Markers?
In conclusion, using tumor markers to diagnose and monitor endometriosis shows promise. It may also potentially detect possible malignant changes at an earlier stage with regular follow-up examinations. However, a significant challenge remains in the current disagreement regarding the precise diagnostic values for these markers. Fluctuations during the menstrual cycle contribute to this challenge, and differing opinions among researchers further complicate the matter. Due to these uncertainties, it is premature to rely solely on determining tumor markers in blood or other bodily fluids to diagnose endometriosis. Nonetheless, the CA-125 marker is valuable in supporting suspicions of its presence. When typical symptoms and elevated CA-125 levels in the blood are present, these indicators provide critical support for diagnosing the condition. However, it is essential to note that average CA-125 values do not definitively rule out the presence of endometriosis. Therefore, abdominal endoscopy remains a necessary procedure for confirmation. While introducing tumor markers as a standard diagnostic tool may require further research and refinement, they hold significant potential for replacing the time-consuming laparoscopy and providing more reliable confirmations or exclusions of endometriosis.
References
- Krebsinformationsdienst: Biomarker:Beispiele https://www.krebsinformationsdienst.de/untersuchung/molekulare-diagnostik/tumormarker-biomarker-beispiele.php (abgerufen am 24.03.2023)
- Die Techniker Krankenkasse: Was sind Tumormarker? https://www.tk.de/techniker/gesundheit-und-medizin/behandlungen-und-medizin/krebserkrankungen-oder-tumoren/was-sind-tumormarker-2018024 (abgerufen am 24.03.2023)
- National Cancer Institute: Tumor Markers https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet (abgerufen am 24.03.2023)
- Bayerische Krebsgesellschaft: Was sind Tumormarker? https://www.bayerische-krebsgesellschaft.de/informationen/fakten-ueber-krebs/16-fragen-zum-thema-krebs/was-sind-tumormarker/?L=0 (abgerufen am 24.03.2023)
- Abrão MS, Podgaec S, Pinotti JA, de Oliveira RM. Tumor markers in endometriosis. Int J Gynaecol Obstet. 1999 Jul;66(1):19-22. doi: 10.1016/s0020-7292(99)00046-6. PMID: 10458545.
- Nonogaki H, Fujii S, Konishi I, Nanbu Y, Kobayashi F, Mori T. Serial changes of serum CA125 levels during menstrual cycles. Asia Oceania J Obstet Gynaecol. 1991 Dec;17(4):369-78. doi: 10.1111/j.1447-0756.1991.tb00288.x. PMID: 1801684.
- Abrão MS, Podgaec S, Filho BM, Ramos LO, Pinotti JA, de Oliveira RM. The use of biochemical markers in the diagnosis of pelvic endometriosis. Hum Reprod. 1997 Nov;12(11):2523-7. doi: 10.1093/humrep/12.11.2523. PMID: 9436699.
- Kraśnicki D. Ocena stezenia CA-125 w płynie otrzewnowym i surowicy u kobiet z endometrioza [Serum and peritoneal fluid CA-125 concentration in women with endometriosis]. Ginekol Pol. 2001 Dec;72(12A):1365-9. Polish. PMID: 11883280.
- Öffentliches Gesundheitsportal Österreichs: CA 19-9 https://www.gesundheit.gv.at/labor/laborwerte/hormone-tumormarker/ca-19-9.html (abgerufen am 24.03.2023)
- Öffentliches Gesundheitsportal Österreichs: CA 15-3 https://www.gesundheit.gv.at/labor/laborwerte/hormone-tumormarker/ca-15-3.html (abgerufen am 24.03.2023)
- Shen A, Xu S, Ma Y, Guo H, Li C, Yang C, Zou S. Diagnostic value of serum CA125, CA19-9 and CA15-3 in endometriosis: A meta-analysis. J Int Med Res. 2015 Oct;43(5):599-609. doi: 10.1177/0300060515583076. Epub 2015 Aug 5. PMID: 26246541.
- Yonghua Chen, Meixia Pan, Ying Zuo, Bin Yang, Shaoguang Wang, Research progress of CA125 in endometriosis: Teaching an old dog new tricks, Gynecology and Obstetrics Clinical Medicine, Volume 2, Issue 4, 2022, Pages 191-198, ISSN 2667-1646, https://doi.org/10.1016/j.gocm.2022.10.006. (https://www.sciencedirect.com/science/article/pii/S2667164622000926)
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