Ovarian Cancer and CA-125
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Direct answer
Ovarian cancer is a malignancy of the ovary, most often of epithelial origin and most commonly high-grade serous, and it is usually diagnosed late because early symptoms are vague. CA-125 is a glycoprotein marker raised in most serous and endometrioid tumours, but it is also raised in endometriosis, fibroids and infection. Because of this, CA-125 is used to monitor treatment rather than to screen the general population.
What you must remember
- Commonest type: epithelial tumours make up about 90 percent of ovarian malignancies, and high-grade serous carcinoma is the commonest malignant subtype.
- CA-125: a MUC16 glycoprotein that is raised in most serous and endometrioid cancers, and is often normal in early disease.
- Germ cell markers: alpha-fetoprotein for yolk sac tumour, beta-hCG for choriocarcinoma, and LDH for dysgerminoma.
- Krukenberg tumour: bilateral ovarian metastasis, most often from a gastric signet ring cell carcinoma.
- Staging: stage I is confined to the ovaries, stage III involves peritoneal or nodal spread, and stage IV includes distant spread and pleural effusion with positive cytology.
- Risk factors: nulliparity, BRCA1 and BRCA2 mutations and Lynch syndrome; combined oral contraceptives reduce the risk.
- Primary treatment: cytoreductive surgery with platinum and taxane chemotherapy, with maintenance PARP inhibitors in selected patients.
How tumour markers guide the diagnosis
A 52-year-old woman with a complex adnexal mass, ascites and a raised CA-125 needs a histology-based interpretation. Each ovarian tumour type carries its own marker, which helps narrow the differential before surgery.
| Tumour type | Typical marker | Key feature |
|---|---|---|
| High-grade serous carcinoma | CA-125 | Commonest malignant subtype; psammoma bodies |
| Endometrioid carcinoma | CA-125 | Associated with endometriosis and endometrial cancer |
| Mucinous carcinoma | CEA, CA 19-9 | Often a metastasis from the gastrointestinal tract |
| Yolk sac tumour | Alpha-fetoprotein | Young women; Schiller-Duval bodies |
| Dysgerminoma | LDH, beta-hCG | Radiosensitive; equivalent of seminoma |
| Granulosa cell tumour | Inhibin | Oestrogen-producing; Call-Exner bodies |
Marker patterns support the diagnosis but never replace histology, which remains the reference standard. Surgical staging and frozen section decide the definitive management, and a rising marker after treatment suggests recurrence.
In serous disease, a rising CA-125 during follow-up may appear before clinical or radiological recurrence. Serial values are therefore read alongside imaging, never as a stand-alone trigger for treatment.
Where the exam tries to catch you
Viva and MCQ questions often test whether the candidate knows which marker belongs to which histology and why CA-125 is not a screening test.
- Trap: CA-125 is a screening test for ovarian cancer. Correct: it is raised in endometriosis, fibroids, infection and pregnancy, and is often normal in early disease, so it is not recommended for population screening.
- Trap: a raised AFP suggests serous ovarian cancer. Correct: AFP points to yolk sac tumour or another germ cell tumour, which typically affects girls and young women.
- Trap: ovarian cancer in a young woman is usually epithelial. Correct: germ cell and sex cord stromal tumours are relatively more common in young women, whereas epithelial tumours dominate after the menopause.
- Trap: a bilateral ovarian mass is always a primary ovarian cancer. Correct: a Krukenberg tumour is a bilateral metastasis, so the stomach and other sites must be examined.
Frequently asked questions
What is a Krukenberg tumour?
A Krukenberg tumour is a bilateral ovarian metastasis, most often from a gastric signet ring cell carcinoma. The ovaries are enlarged and solid, and the stroma contains signet ring cells on histology. The primary site must be sought in the stomach, colon or breast, because management differs from primary ovarian cancer.
Which ovarian tumour is most strongly linked to raised alpha-fetoprotein?
Yolk sac tumour is the ovarian tumour most strongly linked to raised alpha-fetoprotein. It occurs mainly in girls and young women, and Schiller-Duval bodies are a characteristic histological clue. Serial alpha-fetoprotein levels are used to monitor the response to chemotherapy.
What is Meigs syndrome?
Meigs syndrome is the triad of an ovarian fibroma or fibrothecoma, ascites and pleural effusion, usually right-sided. The ascites and effusion resolve after the tumour is removed. Ovarian malignancy must still be excluded, because the picture can mimic advanced cancer.
Why is CA-125 not used for ovarian cancer screening?
CA-125 is not used for ovarian cancer screening because it is raised in endometriosis, fibroids, pelvic infection and pregnancy, and it is often normal in early disease. Its main role is monitoring response to treatment and detecting recurrence in patients with serous ovarian cancer. A normal value does not exclude an ovarian malignancy.
What is the first-line treatment for advanced epithelial ovarian cancer?
First-line treatment for advanced epithelial ovarian cancer is cytoreductive surgery followed by platinum and taxane chemotherapy, usually carboplatin with paclitaxel. Neoadjuvant chemotherapy is an option where complete resection is not feasible at the outset. Maintenance PARP inhibitors are added in selected patients, particularly those with BRCA mutations or homologous recombination deficiency.