Tumor Markers CA-125 and HE4: What the Tests Show

A referral for a CA-125 or HE4 test often frightens more than the lab queue itself. Let us explain what these proteins are, why the number on the form can be above normal, and in which cases it truly requires further evaluation.

What CA-125 and HE4 Are

CA-125 is a protein referred to in laboratory practice as carbohydrate antigen 125 or mucin-16; it is encoded by the MUC16 gene. In a healthy body it is present in the tissue of the eye, endometrium, and in uterine fluid, but it does not enter the bloodstream.

HE4 is another marker studied in ovarian cancer; in the literature it is compared with CA-125 and the ROMA algorithm.

What the Ovarian Tumor Marker Shows

The reference values for CA-125 are less than 35 IU per milliliter. Exceeding this threshold is considered a weighty argument in favor of a malignant ovarian tumor, but not proof. The sensitivity of the test in serous cancer depends on the stage: about 42% at stages I–II and almost 100% at stage IV.

The marker is of little use for early detection. With minimal malignant involvement, the level hardly differs from normal, and at stage I an elevation occurs in no more than half of patients. In mucinous adenocarcinomas, CA-125 remains normal in 32% of cases, in endometrioid tumors in 30–60%, and in clear cell tumors in 40%. At stages II, III, and IV, the value may exceed normal severalfold.

More often CA-125 works not as a search for disease but as monitoring: of the course of the process, of metastases before symptoms appear, and of response to therapy. A change in level coincides with the clinical course in 87–94% of cases.

When CA-125 and HE4 Tests Are Ordered

The reason for a referral is symptoms resembling an ovarian tumor: pain, swelling or a feeling of pressure in the abdomen and pelvis, frequent urges to urinate, difficulty eating and a feeling of fullness, a mass in the pelvic area, bloating, and constipation. A CA-125 blood test is included in the list of investigations along with examination and imaging.

Ovarian cysts are among the non-tumor causes of elevated CA-125, so a single result is not enough. This is a blood test; ask how to prepare for the blood draw when scheduling at your laboratory.

How to Read the Result and Why the Marker Is Sometimes Elevated Not Only in Cancer

The specificity of CA-125 is low, especially in women over 50. The causes of elevation are varied:

• non-tumor processes — inflammation in the abdominal cavity and pelvis, menstruation, endometriosis, adnexitis, ovarian cysts;
• somatic diseases — peritonitis and pleuritis, chronic hepatitis and liver cirrhosis, chronic pancreatitis, autoimmune diseases;
• pregnancy — the level may be elevated in the first trimester;
• tumors — ovarian cancer (about 80% of cases of elevation), as well as cancer of the uterus and endometrium, fallopian tubes, breast, pancreas, stomach, lungs, and liver.

In most non-tumor situations, the concentration does not exceed 100 IU per milliliter.

Why the Test Does Not Make a Diagnosis and What Is Needed Next

A single lab form does not replace an examination. The doctor takes a history, including family history, performs an examination with a gynecological evaluation, and orders imaging and a CA-125 blood test. Ultrasound may be transvaginal or external, through the anterior abdominal wall. If the results are concerning, the patient is referred to a gynecologic oncologist for further investigations. At the appointment, CT, needle biopsy, laparoscopy, or laparotomy are discussed. The most accurate answer is usually provided by a tissue biopsy taken during surgery.

After surgery, CA-125 is often higher than before it during the first two weeks because of tissue damage, so it makes sense to assess it after about a month. In remission, the value stays near the lower limit of normal; a rise even within the normal range — from zero to 35 Units per milliliter — is regarded as a possible preclinical sign of recurrence. A persistently elevated level more often indicates a poor response to treatment and continued tumor growth.

An elevated CA-125 or HE4 on its own is not a reason to call an ambulance; 103/112 — for life-threatening conditions, for example signs of stroke or heart attack.

This material is for reference and does not replace a doctor's consultation.

This content is for reference and does not replace a doctor's consultation. Medical disclaimer