Objective: To evaluate the potential diagnostic role of the myoepithelial marker p63 in fine needle aspiration cytology (FNAC) of breast in comparison to other diagnostic tools. Study Design: A total of 49 FNAC of breast were assessed according to clinical, mammographic, cytological findings, and p63 immunostaining on FNAC. The strength of agreement with final histological diagnosis (FHD) was measured by kappa test. Results: p63 was positive in myoepithelial cells of 75% (9/12) of benign cases and negative in 89% (33/37) of the malignant cases with strong agreement with the FHD (p < 0.0001, ĸ = 0.63). All the malignant positive cases showed variable degrees of in situ component. Only one malignant case (1/37, 0.03%) showed few p63 positive neoplastic cells in FNAC. Combined FNAC and p63 staining (with <25% cutoff point) to diagnose malignancy showed 100% sensitivity, 75% specificity, 92% positive predictive value, 100% negative predictive value, and 94% diagnostic accuracy. Most of the cytologically suspicious cases (7/9, 78%) showed negative p63 staining results, and all these suspicious cases (100%) proved to be malignant by the FHD. There was poor agreement between diagnosis according to positive background naked nuclei (NN) and the FHD (ĸ = 0.24 and p < 0.0001); however, presence of more than 74% positive NN is strongly suggestive of fibroadenoma. Conclusion: p63 immunostaining with a cutoff value of <25% to diagnose malignancy is a highly sensitive and specific myoepithelial marker which is recommended as an adjuvant tool to FNAC of breast in suspicious cases.

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