High Concordance of p53 Immunohistochemistry Between Cytology and Surgical Specimens Supports Early Classification of Gynecologic Malignancies and Borderline Tumors

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Abstract
Introduction: p53 immunohistochemistry serves as a surrogate for TP53 mutation status and plays a central role in the classification of gynecologic malignancies. However, its reliability in cytology specimens, which often constitute the initial diagnostic material, remains incompletely characterized in routine practice. Materials and Methods: After institutional review board (IRB) approval, we performed a retrospective study of 51 gynecologic malignancies and borderline tumors with paired cytology (body fluids and fine‐needle aspiration specimens) and surgical resections. p53 staining patterns were classified as wild‐type or aberrant (overexpression, null, cytoplasmic). Concordance between specimen types and correlation with TP53 mutational status were assessed. Cytology specimens were fixed in CytoRich Red fixative, while surgical specimens were formalin‐fixed. Results: Overall concordance between cytology and surgical specimens was 100% (51/51 cases), spanning multiple specimen types and tumor categories. Aberrant p53 expression was most commonly characterized by overexpression (62.8%), followed by a null pattern (23.5%). Aberrant p53 expression corresponded with TP53 mutations in all cases with available molecular data. Cytology established the initial diagnosis in 60.8% of cases, highlighting its role in early classification. Conclusion: p53 immunohistochemistry demonstrates highly reproducible, pattern‐based interpretation in cytology specimens, supporting its use as a reliable surrogate for TP53 status at the time of initial diagnosis. These findings reinforce the role of p53 in enabling early and accurate classification of gynecologic malignancies when surgical material is limited or unavailable.

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