CA19-9 Elevation in High-Grade Dysplasia of Villous Adenoma
CA19-9 can be elevated in high-grade dysplasia of villous adenomas, though this is not a consistent or reliable finding, and current guidelines do not support using CA19-9 for diagnosis or surveillance of premalignant colorectal lesions.
Evidence from Guidelines
The most authoritative guidance comes from ASCO, which explicitly states that present data are insufficient to recommend CA19-9 for screening, diagnosis, staging, surveillance, or monitoring treatment of patients with colorectal cancer 1. This recommendation extends to premalignant lesions including adenomas with high-grade dysplasia 1.
Biological Basis for Potential Elevation
Despite the lack of clinical utility, there is biological plausibility for CA19-9 elevation in dysplastic adenomas:
CA19-9 expression increases with neoplastic transformation: Immunohistochemical studies demonstrate that CA19-9 is essentially absent in normal colonic mucosa but becomes expressed in adenomatous polyps, with expression somewhat related to the degree of cellular atypia 2.
High-grade dysplasia shows increased expression: In adenomas, CA19-9 was expressed in 80.6% of cases, and this expression correlated to some extent with the degree of cellular atypia 2. In focal carcinoma within adenoma, CA19-9 was strongly and diffusely expressed in 50% of cases 2.
Villous histology may enhance expression: The monosialosyl Lea antigen (CA19-9) is expressed in the majority of adenomatous polyps regardless of polyp size, villous morphology, or degree of dysplasia, though the specific contribution of villous architecture is not definitively established 3.
Clinical Context and Limitations
Important caveats when interpreting CA19-9 in this setting:
Tissue expression does not equal serum elevation: While CA19-9 may be expressed in dysplastic tissue, positive serum levels are restricted to cases with positive tumor expression, and serum elevation is much less common than tissue expression 4.
Benign conditions cause elevation: CA19-9 can be elevated by numerous non-malignant gastrointestinal conditions including gastritis, peptic ulcer disease, diverticulitis, liver diseases, and any acute or chronic inflammatory state 1.
Genetic factors affect expression: Approximately 5-10% of the population lacks the Lewis antigen and cannot produce CA19-9 regardless of tumor presence 5.
Recommended Approach
If CA19-9 is elevated in a patient with a known villous adenoma with high-grade dysplasia:
Do not rely on CA19-9 for diagnosis or risk stratification of the adenoma itself 1
Complete endoscopic resection with adequate histologic examination remains the gold standard for determining the presence and extent of high-grade dysplasia 1
If CA19-9 is markedly elevated (>100 U/mL), consider evaluation for occult invasive carcinoma or synchronous malignancy elsewhere in the gastrointestinal tract, particularly pancreaticobiliary system 1
Elevated preoperative CA19-9 in the context of colorectal neoplasia has negative prognostic significance if invasive cancer is present 1, 6
The presence of high-grade dysplasia itself warrants close surveillance or complete resection based on established colonoscopy guidelines, independent of any tumor marker values 1.