B25. Tumor markers of malignant ovarian cancer. Diagnosis and treatment of borderline ovarian cancer.

Tumour markers of malignant ovarian cancer

Tumour markers in ovarian cancer are not used for diagnosis but rather for preoperative evaluation and follow-up. They’re not appropriate for screening of the general population.

Several biomarkers are available for ovarian cancer:

• Typical for epithelial tumours
  • CA 125
  • CEA
  • HE4 (human epididymis protein 4)
• Typical for germ cell tumours
  • β-hCG
  • AFP
• Typical for granulosa cell tumours
  • Inhibin B
  • Anti-Müllerian hormone

Of these, CA 125 is the most widely used. Up to 80% of endothelial ovarian cancers will have elevated CA 125. It’s elevated if > 35 units/mL. It’s specificity for ovarian cancer is high in postmenopausal women but low in premenopausal.

CEA can be elevated in many conditions other than ovarian cancer, benign and malignant, including GI tract cancer, smoking, liver disease, gallbladder disease, IBD, etc.

β-hCG and AFP are mostly elevated in germ cell tumours and choriocarcinoma.

Inhibin is only elevated in sex cord-stromal tumours. Oestrogens and androgens could be elevated in these tumours as well.

Biomarker panels

Several biomarker panels, which measures multiple biomarkers, are available. These use multiple biomarkers to assess the likelihood of malignancy in patients with adnexal mass. Combining biomarkers makes them more sensitive and more specific.

• ROMA index is the most important and uses two biomarkers
  • CA 125 and HE4
• OVA1 uses five biomarkers
• Overa uses five different biomarkers

The RMI (Risk of Malignancy Index) can be calculated to predict the risk that an adnexal mass is malignant. This calculation requires ultrasound features and the CA125 level.

Borderline ovarian cancer

Borderline ovarian tumours are tumours of low-grade malignant potential. They are characterised by atypical growth but no stromal invasion. They sometimes have intraperitoneal spread.

They are a type of ovarian epithelial tumours, and the borderline ones account for 15% of these tumours. They mostly affect postmenopausal women. Borderline tumours have an excellent prognosis (5-year survival > 90%).

Classification

The histological types are as for other epithelial ovarian tumours:

• Serous type
• Mucinous type
• Endometrioid
• Clear cell
• Brenner tumour

The serous and mucinous types are the most frequent.

The FIGO classification is used for staging. As it’s not mentioned in the topic name, I assume we don’t need to know it.

Clinical features

Most patients present with an asymptomatic adnexal mass which is discovered on bimanual examination or on ultrasound. Sometimes, patients present with abdominal or pelvic pain or dyspareunia.

Diagnosis and evaluation

Evaluation is as for other ovarian tumours (topic A11). There’s nothing in particular which can distinguish borderline tumours from other tumours clinically. The diagnosis is made pathologically, after surgery.

Treatment

The definite diagnosis, staging, and treatment are based on surgery. Frozen section is commonly performed intraoperatively, and the information is used to help determine the extent of the surgical procedure.

Borderline tumours are (like other epithelial tumours) treated with bilateral salpingo-oophorectomy, total hysterectomy, and pelvic washing.

During laparoscopy or laparotomy, the peritoneal cavity should be inspected for possible metastases, and biopsy should be performed if present. Metastases should be resected.