Chemical Pathology

Ovarian Cancer

Ovarian cancer is the fifth commonest cause of cancer-related deaths among women worldwide and accounts for 4% of all cancer deaths in women. Death from ovarian cancer is strongly related to disease stage: stages 1 and 3 are associated with survival rates of more than 70% and stages 3 and 4 are associated with survival rate of 0% – 20%. In most patients, diagnosis of ovarian cancer is made at an advanced stage because of its non-specific clinical symptoms.

Cancer Antigen-125 (CA-125) is the tumour marker of choice for ovarian cancer. Unfortunately it lacks sensitivity and specificity. The sensitivity of CA-125 is related to the stage of disease i.e. it is only elevated in 50% of patients with stage I, but 80% – 90% of patients with stages 3 – 4. The low specificity of CA-125 is demonstrable by its high concentrations in malignancies of different origin including non-ovarian gynaecologic cancers such as endometrium and epithelial tumours, lung cancer as well as non-epithelial malignancies such as lymphomas. CA-125 may also be found in benign conditions such as effusions, renal and liver failure, ovarian cysts, myomas and endometriosis.

Human Epididymis Protein 4 (HE4) is a protein which has gained clinical use as a tumour marker due to its over-expression in ovarian cancers. HE4 has the same sensitivity as CA-125, but has higher diagnostic specificity in patients with gynaecologic malignancies compared with those with benign gynaecologic tumours. When combined with CA- 125, HE4 increases the potential to discriminate benign from malignant ovarian masses. HE4 is consistently expressed in patients with ovarian cancer.

Risk of Ovarian Malignancy Algorithm (ROMA) classifies patients with pelvic masses as being at low risk or high risk for malignant disease. This calculated algorithm uses both CA-125 and HE4 values in conjunction with menopausal status to generate a risk value. This risk is reported together with CA-125 and HE4 results.

The test has the following limitations: It should not be used in patients

  • younger than 18 years.
  • previously treated for ovarian malignancy.
  • currently on chemotherapy.

HE4 should not be used as a cancer screening test or for monitoring known mucinous or germ cell ovarian tumours.

Interpretation of ROMA values

Premenopausal ROMA > 7.3% = High risk of finding epithelial ovarian cancer
ROMA < 7.4% = Low risk of finding epithelial ovarian cancer
Postmenopausal ROMA > 25.2% = High risk of finding epithelial ovarian cancer
ROMA < 25.3% = Low risk of finding epithelial ovarian cancer

NB: At a set diagnostic specificity of 75%, the sensitivity for classifying patients with epithelial ovarian cancer into a high risk group is 93% with a negative predictive value of 97%.

Test to be ordered: HE4 or ROMA
Sample type: Serum (Gold/SST).

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