Decreased CD34 expression in breast phyllodes tumors: association with malignancy and diagnostic test accuracy meta-analysis

Literature points to an association between CD34 stromal expression and breast phyllodes tumors (PT) grading. We conduct a meta-analysis to investigate this association. Studies assessing PT and reporting CD34 levels were identified, with a total of 399 cases. A meta-analysis was conducted for six studies using diverse cutoffs for CD34 positivity, and a subgroup analysis included three studies applying a ≥ 50% cutoff. In six studies with diverse cutoffs, significant association was found with decreased expression of CD34 in (1) malignant compared to borderline tumors (OR 5.27; CI 1.99–13.93; P < 0.001; I2 = 0%); (2) malignant compared to benign tumors (OR 9.18; 95% CI 3.67–22.64; P < 0.001; I2 = 0%). In three studies adopting a cutoff point of 50%, significant association was found with decreased CD34 expression in (1) malignant compared to borderline tumors (OR 6.69; CI 1.47–30.31; P = 0.01; I2 = 0%); (2) malignant compared to benign tumors (OR 12.74; 95% CI 2.53–64.09; P = 0.002; I2 = 0%). No significant differences in CD34 expression were observed between borderline and benign tumors in both analyses. For malignant PTs, reduced CD34 expression showed a pooled sensitivity of 75.9%, specificity of 56.8%, and AUC of 0.71 in the differential with borderline PTs; while in borderline tumors sensitivity was 50.1%, specificity 61.1%, and AUC 0.56, in the differential with benign. No heterogeneity detected in either analysis (I² = 0.0%). Reduced CD34 expression was significantly associated with malignant PT, while the distinction between borderline and benign lesions did not reach statistical significance. However, its limited diagnostic accuracy suggests that CD34 should be used as an adjunct rather than a standalone marker in tumor grading.