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Cancer Antigens CA 125 and CA 19-9

  • Writer: FibonacciMD
    FibonacciMD
  • Sep 9
  • 7 min read

Updated: Sep 19

Understanding Cancer Antigens CA 125 and CA 19-9: Key Biomarkers in Cancer Detection


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Tumor markers, or cancer antigens, are substances found in the blood, urine, or tissue of some cancer patients. This article will provide an introductory overview of two key tumor markers: CA 125, often used in the management of ovarian cancer, and CA 19-9, a biomarker primarily associated with gastrointestinal cancers like pancreatic cancer. We will explore their clinical significance and applications in monitoring these diseases.


by Cheng-Hung Tai, MD,

Michelle Boyar, MD, and


Cancer Antigen 125

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AKA

  • CA 125

  • CA 125 II

  • CA-125

  • CA-125 II

  • carbohydrate antigen 125

  • carcinoma antigen 125

  • MUC16

  • Mucin 16


Cancer antigen 125 (CA125) is an antigenic tumor marker expressed by epithelial ovarian neoplasms and cells lining various organs such as the endometrium, fallopian tubes, pleura, peritoneum, and pericardium. [1]


Cancer antigen 125 (CA-125) is a human protein that is now used as a biomarker but was first discovered in the early 1980’s as a potential treatment for ovarian cancer.  Levels are often elevated in patients with ovarian cancer. The lack of sensitivity and specificity makes the use of CA-125 for early detection of ovarian cancer controversial. However, levels are often examined to assess response of ovarian cancer patients to treatment.


Many benign conditions can result in an elevation of CA-125 levels, including normal menstruation, pregnancy, endometriosis, uterine fibroids, pelvic inflammatory disease, and liver disease. In addition, elevated CA-125 levels may be seen in other malignancies, such as those affecting the fallopian tubes, endometrium, breast, lung, pancreas, and gastrointestinal tract. Any tumor causing peritoneal disease or carcinomatosis can cause elevated CA-125 levels.


Diagnostic Tests

The original CA-125 test has been used since the 1980s. The more recent CA-125 II test is more specific, but there is no statistical advantage in using one test over the other. Normal laboratory values of each test generally vary depending upon individual laboratory ranges:

  • CA-125: ≤ 35 U/mL

  • CA-125 II: < 20 U/mL


The CA-125 II test is more useful in postmenopausal women with adnexal masses suspicious for malignancy. In premenopausal women, CA-125 values fluctuate with menstruation, which results in its decreased sensitivity and specificity in this population. The American College of Obstetricians and Gynecologists has stated that serum CA-125 levels > 200 U/mL is a criterion for referral to a gynecologist or even a gynecologic oncologist. In the 2011 guidelines, this threshold was removed, and no specific numerical value was assigned; a very elevated CA-125 level and clinical evaluation should dictate further work up by a gynecologist or gynecologic oncologist.


Specimen Requirements and Procedure

When the CA125 assay is used for cancer diagnosis, sampling should not be conducted immediately before or during menstruation because the physiological elevation of the CA125 levels may provide false-positive results.[9][20] The serum samples for CA125 should not be collected within 2 weeks of surgery, as the levels may become falsely elevated secondary to tissue damage. CA125 levels have a half-life of 6 days and may require a few weeks to return to normal levels after surgery. A pre-treatment sample should be used as a reference for evaluating CA125 levels postoperatively.[1] [12]


Clinical Significance

CA125 plays a significant role as a tumor marker, particularly in the preoperative assessment of patients with an adnexal mass and suspected to have an ovarian malignancy.[13] Around 80% of the patients diagnosed with ovarian epithelial carcinoma show elevated CA125 levels, and levels are monitored post-treatment to assess the progression of the disease.[14] The use of CA125 for preoperative assessment is more valuable among postmenopausal women compared to its use among premenopausal women.[4] 

 

CA125 is successfully used for disease monitoring after treatment (chemotherapy or chemotherapy and surgery) and evaluating the progression of the disease. A significant correlation exists between the disease progression and serum CA125 levels, with doubling or halving serum values considered clinically significant.[8]  Most patients with CA125 levels greater than 35 U/mL demonstrate disease recurrence on second-look surgery.[1] [8] 


Prognosis

Preoperative and postoperative CA125 concentrations may be of prognostic significance.[15] After primary surgery and chemotherapy, persistent elevations of CA125 concentrations are associated with poor prognosis. Patients with preoperative CA125 concentrations greater than 65 U/mL are reported to have a lower 5-year survival rate and a 6.37-fold risk of death compared to patients with CA125 levels less than 65 U/mL.[12]  Normalization of CA125 levels after 3 cycles of combination therapy also correlates with improved survival. Importantly, CA125 concentration is not elevated in 10% to 20% of patients with advanced ovarian cancer. For these patients, using radiological imaging techniques and monitoring other tumor markers are necessary.[1][16]


For more information- see National Institutes of Health.  Cancer Antigen 125- StatPearls by T Gandhi 2024 https://www.ncbi.nlm.nih.gov › books › NBK562245



Cancer Antigin 19-9


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AKA

  • CA 19-9

  • CA 19-9

  • CA19-9

  • cancer antigen 19-9

  • carbohydrate antigen 19-9


Cancer antigen 19-9 (CA19-9) is a biomarker that is often elevated in malignancies of the gastrointestinal system, including pancreatic, neuroendocrine, colorectal, gastric, esophageal, and hepatocellular tumors. However, this antigen is also found in normal pancreatic fluid and bile and various benign conditions. Originally discovered as a monoclonal antibody for treatment of colorectal cancer, the current clinical significance of serum CA 19-9 is its usefulness in managing pancreatic cancer.


Clinical Usefulness

The following table depicts the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CA 19-9 with respect to the diagnosis of pancreatic malignancies.


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In one study, the 37 U/mL cutoff for CA 19-9 was the best value for discriminating pancreatic from other malignancies, with relatively low sensitivity (77%) but better specificity (87%). In general, CA 19-9 should not be used as a screening tool for pancreatic cancer.


Serum CA 19-9 levels are useful to evaluate treatment response and determine a prognosis. Recently, higher cutoffs have been used, as this increases specificity at the cost of sensitivity. High levels of CA 19-9 often correlate with unresectable or advanced malignancies, whereas decreasing levels indicate a longer patient overall survival.


As per American Society of Clinical Oncology (ASCO) guidelines, serial monitoring of CA 19-9 levels can be used to assess tumor response to treatment (surgery, chemotherapy, radiation therapy, or targeted therapy). Levels are checked once every 1-3 months. Decreasing levels suggest efficacy of a therapeutic regimen, whereas a rising (or unchanged) level may indicate disease progression and the need for further imaging and/or biopsy. Treatment decisions are not made solely on the basis of a rising or falling CA 19-9 level.


Other Serological Biomarkers for Pancreatic Cancer 

One “marker” under further evaluation for its clinical usefulness is the NLR.   An elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) has been reported to be a negative prognostic marker in many types of cancer, including pancreatic ductal adenocarcinoma (PDAC). [17] 


Ongoing research will analyze a multitude of potential biomarkers (including genetic) for pancreatic and other gastrointestinal malignancies.  Serologic panels will be further developed. These studies will be critical for identifying prognostic biomarkers and potential therapeutic targets.

Courtesy of the National Library of Medicine


References

  1. “Courtesy of the National Library of Medicine” or “Source: National Library of Medicine.”

  2. Bast RC Jr, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB. CA 125: the past and the future. Int J Biol Markers. 1998;13:179-187.

  3. Eltabbakh GH, Gupta MK, Belinson JL, Kennedy AW, Webster K, Paraiso MF. Comparison between Centcor CA-125 and CA-125 II assays. Eur J Gynaecol Oncol. 1996;17:504-506.

  4. 4.  American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Gynecology. Practice Bulletin No. 174: Evaluation and Management of Adnexal Masses. Obstet Gynecol. 2016 Nov;128(5):e210-e226. [PubMed]

  5. Steinberg W. The clinical utility of the CA 19-9 tumor-associated antigen. Am J Gastroenterol. 1990;85:350-355.

  6. Kim HJ, Kim MH, Myung SJ, et al. A new strategy for the application of CA19-9 in the differentiation of pancreaticobiliary cancer: analysis using a receiver operating characteristic curve. Am J Gastroenterol. 1999;94:1941-1946.

  7. Locker GY1, Hamilton S, Harris J, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;22:5313-5327.

  8. Kenemans P, Yedema CA, Bon GG, von Mensdorff-Pouilly S. CA 125 in gynecological pathology--a review. Eur J Obstet Gynecol Reprod Biol. 1993 Apr;49(1-2):115-24. [PubMed]

  9. Grover S, Koh H, Weideman P, Quinn MA. The effect of the menstrual cycle on serum CA 125 levels: a population study. Am J Obstet Gynecol. 1992 Nov;167(5):1379-81. [PubMed]

  10. American College of Obstetricians and Gynecologists Committee on Gynecologic Practice. Committee Opinion No. 477: the role of the obstetrician-gynecologist in the early detection of epithelial ovarian cancer. Obstet Gynecol. 2011;117:742-746.

  11. Balachandran A, Nayak SR. An Observational Study of Factors affecting CA125 Levels in Premenopausal Women. Adv Biomed Res. 2023;12:235. [PMC free article] [PubMed]

  12.  Meyer T, Rustin GJ. Role of tumour markers in monitoring epithelial ovarian cancer. Br J Cancer. 2000 May;82(9):1535-8. [PMC free article] [PubMed]

  13. Dodge JE, Covens AL, Lacchetti C, Elit LM, Le T, Devries-Aboud M, Fung-Kee-Fung M., Gynecology Cancer Disease Site Group. Preoperative identification of a suspicious adnexal mass: a systematic review and meta-analysis. Gynecol Oncol. 2012 Jul;126(1):157-66. [PubMed]

  14. Prat J., FIGO Committee on Gynecologic Oncology. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet. 2014 Jan;124(1):1-5. [PubMed]

  15. Cooper BC, Sood AK, Davis CS, Ritchie JM, Sorosky JI, Anderson B, Buller RE. Preoperative CA 125 levels: an independent prognostic factor for epithelial ovarian cancer. Obstet Gynecol. 2002 Jul;100(1):59-64. [PubMed]

  16. Lee M, Chang MY, Yoo H, Lee KE, Chay DB, Cho H, Kim S, Kim YT, Kim JH. Clinical Significance of CA125 Level after the First Cycle of Chemotherapy on Survival of Patients with Advanced Ovarian Cancer. Yonsei Med J. 2016 May;57(3):580-7. [PMC free article] [PubMed]

  17. Li J, Wang J, Li Y, Jiang W, Zuo D, Zhang X, Xiao J, Inamura K, Giovannetti E, Ren, L. Peripheral blood neutrophil-to-lymphocyte ratio as a prognostic marker and its association with the tumor-immune microenvironment in pancreatic cancer: a retrospective cohort study. J Gastrointest Oncol. 2025 Jun 25;16(3):1248–1257. doi: 10.21037/jgo-2025-283

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