Tumor markers are biological substances found in the blood, urine, or body tissues. Produced by cancer cells or the body’s response to cancer or certain non-cancerous conditions, they serve as indicators that may provide information about a cancer’s presence, progression, or response to treatment. These markers can be proteins, other substances, or genetic markers like gene mutations.
Key Tumor Markers for Uterine Cancer
For uterine cancer, particularly endometrial cancer, Cancer Antigen 125 (CA-125) and Human Epididymis Protein 4 (HE4) are key tumor markers. CA-125 is a glycoprotein often used for monitoring ovarian cancer. Its normal threshold is often considered around 35 U/mL.
HE4 is a whey acidic protein that has shown promise as a diagnostic marker for endometrial cancer and is associated with disease severity. While both markers can be elevated in the presence of uterine cancer, HE4 often exhibits higher sensitivity for endometrial cancer compared to CA-125, with a common threshold of 70-77 pmol/L. HE4 may also be superior to other tumor markers in detecting early endometrial cancer.
Combining CA-125 and HE4 can improve diagnostic accuracy for endometrial cancer. A combination of these markers has shown higher sensitivity and specificity than either marker alone in predicting and monitoring recurrence in type II endometrial carcinoma. This combination can also differentiate between benign and malignant endometrial conditions.
Role in Uterine Cancer Management
Tumor markers like CA-125 and HE4 are valuable tools in the management of uterine cancer, though rarely for initial diagnosis alone. Their primary application lies in monitoring treatment response. Healthcare providers track the levels of these markers during chemotherapy or other treatments to assess treatment effectiveness. A decrease in marker levels often indicates effective treatment and reduced tumor burden.
These markers are also used to detect recurrence after treatment. Rising levels of CA-125 or HE4 following the completion of therapy can signal that the cancer has returned, prompting further investigation. HE4 levels at primary diagnosis and recurrence have shown a significant difference between recurrent and non-recurrent type II endometrial carcinoma patients.
Tumor markers can also assist in risk assessment, particularly for endometrial cancer. Preoperative HE4 levels may help evaluate the risk factors for type II endometrial carcinoma. While not used for initial diagnosis, these markers, when combined with other diagnostic information, can assess cancer spread or severity before surgical intervention.
Interpreting Results and Limitations
Elevated tumor marker levels do not definitively confirm the presence of cancer, nor do normal levels entirely rule it out, due to false positives and false negatives. Elevated CA-125 levels, for example, can occur in various non-cancerous conditions such as menstruation, pregnancy, endometriosis, pelvic inflammatory disease, or uterine fibroids. Liver disease, arthritis, and diverticular disease can also cause elevated CA-125.
Similarly, HE4 levels can be falsely elevated by conditions like renal failure, hypertension, diabetes, and increase with age. Conversely, some cancers may not produce elevated markers, or levels might remain within the normal range in the early stages of the disease, leading to false negative results. About half of early-stage ovarian cancers, for instance, may present with normal CA-125 levels.
Therefore, tumor marker results must always be interpreted by a healthcare professional within the broader context of the patient’s clinical picture. This includes combining marker levels with other diagnostic tools like imaging studies (MRI, ultrasound), biopsies, and physical examinations. This combined information provides a comprehensive understanding of the patient’s condition and guides management decisions.