CA-125

CA-125 is a high-molecular-weight glycoprotein found on the surface of Mullerian and celomic epithelial-derived cell types and is the best known tumor marker for epithelial ovarian cancer . Importantly, it may also be elevated in several other conditions (see differential diagnosis section below).

Limitations as tumor marker

Serum concentrations of CA-125 ≥35 U/mL are associated with ovarian epithelial malignancy. However, there are several limitations with using CA-125 as a biomarker :

  • low sensitivity during early disease (~50%)
    • levels significantly elevated in only ~50% women diagnosed with stage I or II ovarian cancer
  • normal levels in 20% of ovarian malignancies
  • elevations in other benign and malignant processes

Clinical applications

Still, serum CA-125 level is useful in several aspects of the management of ovarian cancer:

  • it may help in the early detection of malignancy, as elevated levels may precede clinical detection by more than a year
    • there is no recommendation for use for ovarian cancer screening in the general population
  • measurement may be useful in the evaluation of an indeterminate adnexal lesion (although still non-specific)
  • degree of elevation is useful for prognostication, as the risk of dying of disease is higher in patients with a higher serum level of the marker
  • trajectory of serum concentration may be used to assess treatment response and for detection of recurrence
    • negative CA-125 level and imaging cannot exclude recurrent disease, only detected by repeat laparotomy

History and etymology

CA-125 was indirectly discovered during experiments in designing monoclonal antibody which selectively bound to cancer cells. In 1981, Bast et al. created an antibody (OC125) which specifically bound to the surface of ovarian cancer cells, by immunising mice with human serous papillary cystadenocarcinoma cancer cells. In the original experiments, it was noted that the antibody also reacted to a melanoma cell line .

Differential diagnosis

Serum CA-125 level may be elevated in a number of benign and malignant conditions , and may even be seen in some (~1%) normal healthy patients .

Malignancy
Benign conditions
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