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Ovarian Tumour Markers-false positives

Posted by Professor Mike O’Connor AM on 21 November 2016

The use of ovarian tumour mark-ers, like those for other tumours, are used both to suggest the presence of a tumour as well as monitor its remission after de-finitive treatment. The problem is the lack of specificity which means that many non malignant processes can be associated with elevated values or that the malignancy is non-gynaecological.

CA125. Cancer antigen 125 (CA 125) is used the most extensively. Approximately 60% of malignant ovarian tumours are associated with an elevated CA125-often the level being >200 U/ml. Other diagnos-tic tests for epithelial ovarian cancer in-clude human epididymis protein (HE4), the OVA1 panel, and the Risk of Malig-nancy Algorithm (ROMA).

The CA 125 antigen is a large transmembrane glycoprotein derived from both coelomic (pericardium, pleura, peri-toneum) and müllerian (fallopian tubal, endometrial, endocervical) epithelia .The antigen is not specific to ovarian cancer as raised serum levels may also be found in 29% of other cancers (lung, breast, pan-creas, and colo-rectum) and in 6% of women with non-malignant conditions such as cirrhosis with ascites, acute pan-creatitis, ovarian cysts, endometriosis, and pelvic inflammatory disease. A Norwegian study showed that approximately 25% of blood samples had raised serum CA125 levels within 60 months preceding the di-agnosis of ovarian cancer .CA125 can be used to monitor the efficacy of treatment for ovarian cancer.

Cancer antigen 19-9 (CA 19-9) is a mucin protein that may be elevated in ovarian cancer or mucinous benign ovarian tu-mours. It may be elevated in endometrio-sis.

CA 19-9 is used primarily to monitor dis-ease response to therapy or detect cancer recurrence in patients with a documented gastric cancer, pancreatic cancer, gallbladder cancer, cholangiocarcinoma, or adenocarcinoma of the ampulla of Va-ter.

Endometriosis & CA125
Plasma concentrations of CA125 are markedly elevated in women with cystic ovarian endometriosis and/or deeply infil-trating endometriosis, but not, or only slightly, in the luteal phase of women with minimal or mild endometriosis .Overall the incidence of a raised CA125 is ap-proximately 30%.Serum CA125 is not a good marker for endometriosis but it is a helpful additional parameter to diagnose endometriotic disease in patients with chronic pelvic pain. Following treatment of endometriosis, elevated plasma concen-trations of CA125 can be used to signal that treatment has been incomplete, or that the condition has recurred .In clini-cal practice, 93% of women with a serum CA-125 level of 30 U/mL or higher who have had the diagnoses of adenomyosis, leiomyomas, ovarian tumors, pelvic in-flammation, and/or pregnancy ruled out will be shown to have endometriosis on further diagnostic testing .


Ovarian Cancer may originate in the Fallopian Tube

HE4 The human epididymis protein 4 (HE4) is elevated in patients with serous or endometrioid ovarian carcinoma. It is also used for the evaluation of an adnexal mass as a component of the Risk of Malignancy Algorithm (ROMA). False positives occur
with impaired renal function.

High-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian cancer. Research over the past decade has strongly suggested that "ovarian" HGSC arises in the epithelium of the distal fallopian tube, with serous tubal intraepithelial
carcinomas (STICs) being detected in 5-10% of BRCA1/2 mutation carriers undergoing risk-reducing surgery and up to 60% of unselected women with pelvic HGSC

About 75-80% of women with advanced ovarian cancer will have an elevated CA125 but only 50% of early ovarian cancers have a raised CA125.



Author:Professor Mike O’Connor AM

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