What does an elevated Carcinoembryonic Antigen 72-4 (CA 72-4) level indicate?

Elevated CA 72-4: Clinical Significance and Diagnostic Approach

An elevated CA 72-4 level most strongly suggests gastric adenocarcinoma, though it can also indicate other gastrointestinal malignancies, ovarian cancer, or malignant cystic liver lesions. 1, 2

Primary Malignancies Associated with Elevated CA 72-4

Gastric Cancer (Strongest Association)

• CA 72-4 demonstrates the highest diagnostic utility in gastric adenocarcinoma, with sensitivity of 59-68% and specificity of 91-98% 1, 2, 3
• Elevated levels correlate strongly with lymph node involvement: only 13.5% positive in node-negative disease versus 50% in patients with N2 disease 4
• Higher levels are found in advanced stages (III-IV), though 80% of stage I patients may also show elevation 3
• Patients with liver metastases demonstrate particularly elevated CA 72-4 levels 5
• Combining CA 72-4 with CA 19-9 increases detection to 70% of gastric cancers 1, 2

Other Gastrointestinal Malignancies

• Colorectal cancer: 32% sensitivity (inferior to CEA at 58%) 2
• Pancreatic cancer: 22% sensitivity (markedly inferior to CA 19-9 at 82%) 2
• Cholangiocarcinoma: CA 72-4 may be elevated but is not the primary marker 1

Gynecological Malignancies

• Ovarian cancer: approximately 50% sensitivity with >95% specificity 6
• Should be combined with CA 125 for optimal monitoring 6

Hepatic Cystic Lesions

Malignant Cystic Liver Disease

• CA 72-4 (TAG-72) in cyst fluid >25 U/ml has the best diagnostic capability for distinguishing malignant hepatic cysts from benign cysts (sensitivity 79%, specificity 97%, AUC 0.98) 1
• This is superior to CEA (AUC 0.71, accuracy 22%) and CA 19-9 (AUC 0.71, accuracy 19%) for hepatic cyst differentiation 1
• Note: This applies to cyst fluid analysis, not serum levels 1

Benign Conditions Causing Elevation

Key Distinguishing Feature: Exceptional Specificity

• CA 72-4 has very high specificity (98%) in benign gastrointestinal diseases, including inflammatory processes 2
• This is substantially higher than CEA or CA 19-9 specificity in benign conditions 2
• Benign gastrointestinal diseases rarely cause false-positive elevations 2, 3

Pericardial Effusions

• CA 72-4 may be measured in pericardial fluid for suspected malignant effusions, though diagnostic accuracy remains controversial 1
• Multiple tumor markers including CA 72-4 have not proven accurate enough to distinguish malignant from benign pericardial effusions 1

Diagnostic Algorithm for Elevated Serum CA 72-4

Immediate Evaluation

1. Perform upper endoscopy with biopsy as the priority investigation given gastric cancer's strongest association 2, 3, 5
2. Obtain contrast-enhanced CT of chest, abdomen, and pelvis to evaluate for metastatic disease and identify primary tumor site 7
3. Consider colonoscopy if upper endoscopy is negative 2

Additional Testing Based on Initial Results

• If gastric cancer suspected but endoscopy negative: repeat endoscopy with extensive biopsies, consider endoscopic ultrasound 3
• In women with negative GI workup: pelvic ultrasound and CA 125 measurement for ovarian cancer 6
• If hepatic cysts identified on imaging: consider cyst fluid aspiration for CA 72-4 measurement if malignancy suspected 1

Monitoring Considerations

• CA 72-4 is valuable for detecting recurrence in gastric cancer patients, with significant elevations predictive of recurrent disease 6, 4
• Serial measurements more useful than single values for monitoring known malignancy 6
• Combination with CEA and CA 19-9 increases sensitivity without substantially reducing specificity 2, 6

Critical Clinical Pitfalls

Do Not Dismiss Elevated CA 72-4

• Given its 98% specificity, elevated CA 72-4 should always be taken seriously and warrants thorough malignancy evaluation 2
• Unlike CA 19-9 (elevated in cholangitis) or CEA (elevated in benign liver disease), CA 72-4 rarely elevates in benign conditions 2

Recognize Limitations

• Approximately 40% of gastric cancers will have normal CA 72-4 levels 2, 3
• Early-stage disease may not elevate CA 72-4, though some stage I patients do show elevation 3
• CA 72-4 is not useful for population screening due to insufficient sensitivity 2