Comparison of the Mitotic Count With Various Proliferative Markers for the Effective Differentiation of Benign, Borderline, and Malignant Phyllodes Tumors

Introduction Phyllodes tumors of the breast are categorized as benign, borderline, or malignant based on the WHO classification, which provides comprehensive criteria for determination, such as stromal cell density, stromal cell atypia, mitotic count, borderline status, and presence of ectopic stromal components. The present study was conducted to determine whether there is a proliferative marker superior to mitotic count. Methods The cohort comprised 47 benign, 13 borderline, and 16 malignant phyllodes tumors classified according to the WHO criteria. Various cell cycle-related proteins, including Ki-67, Cyclin A2, Cyclin B1, Cyclin E, phospho-histone H3, and Survivin, were used as proliferation markers. Cutoff values, sensitivity and specificity, and positive predictive value (PPV) were determined using the receiver operator characteristic (ROC) analysis. Results When comparing sensitivity and specificity using cutoff values to differentiate malignant phyllodes tumors from benign and borderline phyllodes tumors separately, only mitotic count alone showed a value exceeding 0.9. Additionally, the mitotic count showed a PPV greater than 0.8 in all three types of differentiation. However, when differentiating between benign and borderline phyllodes tumors, none of the proliferative indices, including mitotic count, exhibited a value greater than 0.9 for both sensitivity and specificity, and the PPV for borderline tumors did not exceed 0.4. Conclusion These findings suggest that mitotic count is the most reliable index for assessing proliferation, for differentiation of malignant from benign or borderline phyllodes tumors. Furthermore, it was revealed that criteria other than the proliferation index play a crucial role in distinguishing between benign and borderline phyllodes tumors.