Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
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        CA 125 Test, Blood
      
CA 125 antigen, serum

This is one of the  carbohydrate (glycoprotein) cancer antigens (CA) which may circulate in the blood of patients with ovarian and other adenocarcinomas...casually considered to be an "ovarian cancer marker"...a serum cancer marker.  An ovarian cancer (OC125) cell line is cultivated and maintained to produce cancer cells which are injected into mice to produce antibodies against the OC125 cells. The murine (mouse) lymphocytes are harvested and grown to produce the antibodies at commercial volumes1. CA125 increases in serum as a result of any benign or malignant  process which stimulates peritoneal tissue synthesis2. It is to follow cases of ovarian cancer for recurrence.

Screening Test: Where a combination of factors indicates screening is advisable, CA125 plus transvaginal ultrasound continue to be the mainstay of screening6. It is akin to a "sed rate" test, an "ANA" test, or a "CBC" test because we conventionally consider normal results to indicate a "normal" person. Beyond that, the value of the CA125 test is dependent on how it is used.

  • general screening not indicated: Were it to be used as a general screening test for ovarian cancer, the false positive results (ovarian cancer being fairly rare) would probably outnumber true positive results by over 100 fold. That is, for every 100 women who would be thrown into a panic by an elevated result, no more than 1 would actually have ovarian cancer. Women who want to take charge of their health status can best help themselves by first mapping out a family history of which ancestors and aunts and uncles had what types of cancer HERE.
  • screening of increased-risk patients: If cancer "runs" in the family, particularly breast, ovarian, and colonic, periodic CA125 screening2 and ultrasound examination of the ovaries might be worthwhile. If it is above 200 in a premenopausal woman or above 35 in a postmenopausal woman, then a serious investigation may be warranted HERE. (see this ARUP file) Human epididymus protein 4 (HE4) secreted in high levels by cancer but not benign processes is FDA approved (as od 2012) for monitoring for recurrence or progression but not for screening9.
  • New mass evaluation: It may be helpful, off label, in the initial evaluation of a newly discovered mass of the ovary HERE.

 

Conditions Causing Elevations of this Marker:

  • 1% of perfectly normal [warning] women1
  • Any benign irritation or inflammation of the abdominal (peritoneal) lining membrane, such as:
    • menstuation2
    • during the several days following monthly rupture of the ovum from the ovary, if there is any hemorrhage
    • rupture of the monthly corpus luteum of the ovary (common)
    • pregnancy2
    • endometriosis (common)2, 3
    • peritoneal effusion for any reason2
    • chronic liver disease, cirrhosis2, 3
    • renal failure and/or UTI2, 3
    • PID (pelvic inflammatory disease...common) or abscess3
    • postoperative peritoneal adhesions that are "irritated"
    • bowel obstruction3
    • chronic peritonitis
    • abdominal or pelvic irradiation (as in radiation therapy)
  • benign multicystic mesothelioma of peritoneum (BMMP)
  • other benign tumors lining or protruding above the peritoneum and periodically being mechanically irritated...leiomyoma of uterus2, 3
  • non-mucinous tumors of the ovary (benign or malignant)
  • primary benign or malignant proliferations or cancers of the peritoneal membranes
  • intrauterine endometrial cancer may elevate and >65 U/mL means endometrial cancer has likely gone extrauterine2
  • metastatic tumors (such as endometrial, colonic, or breast to the ovaries...Krukenburg tumors) to the peritoneal membranes.
  • cirrhosis or advanced fibrosis combination raise CA125 & CA19-98.
  • non-abdominal disorders:
    1. pleural effusion2, 3
    2. pulmonary embolism
    3. congestive heart failure2
    4. pneumonia3
    5. Dressler's syndrome3
  • when there is an abdominal tumor mass, even high levels do not distinguish benign vs. malignant; and the primary malignancies can be one of any organ or site in the abdominal cavity, including non-Hodgkin's lymphoma2 
  • in following an ovarian cancer case postoperatively, CA125 is only 45% sensitive for recurrences.
  • preoperative vs 5 day postoperative ratios may be helpful in a number of oncological treatment decisions2
  • second-line post-chemo prognostic: a response is defined as a fall in elevated CA-125 levels of at least 50%. The CA-125 criteria were 2.6 times more accurate at predicting survival. On multivariate analysis, the CA-125 response remained a significant predictor of survival, whereas the CT/ultrasound response did not4.
  • but, once a known recurrence has caused an elevation, it may be a useful monitoring test2

Situations Wherein the Level is Not Elevated:

  • any of the above may fail to be elevated because the disorder is too early and for reasons unknown when there is plenty of disease.
  • is not a good screening test for serous ovarian cancer because it is not elevated at the time of diagnosis in 20% of cases2
  • one cause might be patients with heterophile antibodies in their serum against antibody proteins of the animal (e. g., mouse) that generated the reagent test system antibodies...patient antibodies then block the reagent antibodies and yield a false negative test result

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Serum Screening Packages Which Include CA125:

In our opinion, as presented in THIS decision tree, the following are overly expensive and almost certainly noncontributory (above CA-125, possibly plus HE4).

OvaSure: Launched in 2008 (then pulled from the market), it's a blood test by Lab Corp that profiles a series of six serum markers (leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, and CA-125). Some thought it detect ovarian cancer with 99% specificity and 95% sensitivity. Reports of CA-125 sensitivity have it at 72%.

OVA1: Launched 3/2010 by Vermillion and marketed by Quest, it's a blood test that that profiles a series of six serum markers (apolipoprotein A1, beta-2 microglobulin, CA125, pre-albumin, and transferrin).

ROMA: A rival test being developed by Japan's Fujirebio Inc., called Risk of Malignancy Algorithm, or ROMA, was shown in a trial published last year to detect 89% of cancers pre-surgery with only a 25% false-positive rate. Fujirebio is conducting more research and plans to apply for FDA clearance this fall of 1010. The test involves both the CA125 and HE4 markers.

Others:

  • Correlogic Systems Inc., Germantown, Md., is working on something to rival OVA1.
  • Arrayit Corp., Sunnyvale, Calif., says it is working on a screening test, but it isn't clear yet if it will pass muster with the FDA.
  • M. D. Anderson group: they report promising serum test results with a combo of serum CA125 and serum "fingerprinting" by HPLC with high resolution mass spectometry (HRMS) then followed by transvaginal ultrasound unless both are normal6.

References:

  1. The Handbook of Clinical Pathology [text], McKenna & Keffer, 2nd Ed., 2000.
  2. Interpretation of Diagnostic Tests, Wallach, 2000, 7th Ed.
  3. J. Surg. Oncol. 75:264-265, 2000.
  4. J. Clin. Oncology (2004?)...Copenhagen, Denmark group.
  5. WSJ article on OVA1 2010 HERE.
  6. Silva EG, et. al., "A New Approach...", AJCP 134(6):903-909, Dec. 2010.
  7. Gynecologic Tumor Markers @ eMedine web site, scroll down about 3 pages.
  8. Etxagibel A, et. al., "Drug-induced hepatitis superimposed on the presence of anti-SLA antibody: a case report", J Med Case Reports 2:25, 2008.
  9. Konstantinopoulos PA, et. al., "CLINICAL CROSSROADS: Management of Ovarian Cancer", JAMA 307(13):1420-1429, 4 April 2012.
(posted 2001; latest addition 4 April 2012)
 
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