An In-Depth Evaluation of CD15 Expression in Thyroid Carcinoma: A Comprehensive Systematic Review.

Abstract

<h4>Background</h4>Cluster of differentiation 15 (CD15) is a carbohydrate epitope implicated in cell adhesion, migration, and tumor progression. It is variably expressed in thyroid carcinoma (TC) subtypes. However, its diagnostic and prognostic value remains uncertain due to methodological heterogeneity and inconsistent findings.<h4>Aim</h4>To systematically review the prevalence, clinicopathologic associations, and diagnostic utility of CD15 expression across TC subtypes.<h4>Methods and results</h4>Following PRISMA guidelines, a systematic search was conducted in May 2025 across PubMed, Scopus, and Web of Science. Sixteen observational studies evaluating CD15 expression in human TC were included. Risk of bias was assessed using the ROBINS-I tool. A total of 1665 TC cases were analyzed. Classic papillary thyroid carcinoma (CPTC) showed moderate overall prevalence (0%-100%), follicular variant papillary thyroid carcinoma (FVPTC) demonstrated lower expression (17.6%-80%), while tall-cell papillary thyroid carcinoma (TCPTC) exhibited the highest positivity (71%-100%). Follicular thyroid carcinoma (FTC) showed modest expression, whereas medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) demonstrated overall low positivity. CD15 showed high specificity (90%-100%) for PTC, but sensitivity was inconsistent, particularly in follicular variants.<h4>Conclusion</h4>CD15 demonstrates high specificity for PTC. However, its limited sensitivity and variable expression in follicular-patterned lesions make its prognostic value unclear. CD15 should not be used as a standalone marker; instead, it may improve diagnostic accuracy when combined with other markers in multiparametric immunohistochemical panels.