What is Cancer Antigen 72-4 (CA72-4)?
CA72-4 is a tumor-associated glycoprotein (TAG-72) that serves as a serum tumor marker primarily used for monitoring gastrointestinal malignancies, particularly gastric adenocarcinoma, and to a lesser extent ovarian cancer. 1, 2
Biochemical Characteristics
- CA72-4 is a mucin-like, high-molecular-weight glycoprotein identified by two monoclonal antibodies (CC49 and B72.3) that recognize specific glycochain epitopes: Galβ(1-3) sialyl-Tn and sialyl-Tn antigens 3
- The marker is measured using immunoradiometric assay systems with a standard cut-off value of 4.0 U/mL 2
- Modern automated chemiluminescent immunoassays demonstrate high sensitivity with limits of detection at 0.18 U/mL and quantitation at 0.95 U/mL 3
Primary Clinical Applications
Gastric Adenocarcinoma (Highest Utility)
- CA72-4 demonstrates optimal diagnostic performance in gastric cancer with sensitivity of 59-68% and specificity of 91-98% 1
- Combining CA72-4 with CA19-9 increases detection rates to 70% of gastric cancers 1
- Positive rates in gastric cancer patients reach 52% 2
- Elevated levels correlate with advanced disease stages, lymph node involvement, and recurrence 2
Other Gastrointestinal Malignancies
- Colorectal cancer shows 55% positivity rate with approximately 40% sensitivity 2, 4
- Pancreatic adenocarcinoma demonstrates 46% positivity rate 2
- In pancreatic cancer, elevated CA72-4 predicts lymph node metastasis (P<0.001) and poor prognosis, with hazard ratio of 2.34 (95% CI: 1.46-3.73) compared to normal levels 5
- Cholangiocarcinoma may show elevation, though CA72-4 is not the primary marker for this malignancy 1
Hepatic Cystic Lesions (Specialized Application)
- CA72-4 in cyst fluid >25 U/mL provides superior diagnostic capability for distinguishing malignant from benign hepatic cysts, with sensitivity 79%, specificity 97%, and AUC 0.98 1
- This performance exceeds that of CEA and CA19-9 for hepatic cyst differentiation 1
Gynecological Malignancies
- Ovarian cancer shows 50-67% positivity rate 2, 4
- Breast cancer demonstrates 39% positivity rate 2
- Overall sensitivity in ovarian cancer approximates 50% with specificity exceeding 95% 4
Clinical Monitoring Strategy
Disease Surveillance
- CA72-4 is most valuable for longitudinal monitoring of known gastrointestinal and gynecological malignancies, where significant elevations predict recurrent disease 4
- Serial measurements in patients with advanced disease correlate with clinical activity 6
- Higher levels associate with advanced stages and recurrence compared to early-stage disease 2
Combination Marker Approach
- Combining CA72-4 with CEA and CA19-9 for gastrointestinal cancers, or with CA125 for ovarian cancer, increases sensitivity without substantially compromising specificity 4
- This multi-marker strategy improves monitoring capabilities in these patient populations 4
Diagnostic Algorithm for Elevated CA72-4
When CA72-4 is elevated (particularly >25-50 U/mL):
Obtain contrast-enhanced CT of chest, abdomen, and pelvis to evaluate for gastric mass/wall thickening, peritoneal carcinomatosis, hepatic metastases, and lymphadenopathy 1
Perform gastroscopy with multiple biopsies when gastrointestinal primary is suspected 1
Measure concurrent tumor markers: CEA, CA19-9, and CA125 1
If hepatic cysts are identified on imaging, consider cyst fluid aspiration for CA72-4 measurement (>25 U/mL suggests malignancy) 1
Specificity and Benign Conditions
- Overall specificity exceeds 95% across malignancies 4
- Only 10% of patients without malignancy show levels >4.0 U/mL 2
- Average serum level in cancer patients (38.6 U/mL) significantly exceeds that in non-malignant conditions (2.7 U/mL) 2
Prognostic Implications
- Elevated CA72-4 at diagnosis suggests advanced disease with likely lymph node involvement, possible peritoneal or hepatic metastases, and poor prognosis 1
- In pancreatic adenocarcinoma post-radiation therapy, elevated CA72-4 predicts significantly shorter median overall survival (10.0 vs 14.0 months, P<0.001) 5