β-Catenin, PAX2 and PTEN panel in the diagnosis of endometrial precancers: a case-based review

Detection and management of endometrial precancers remain ongoing challenges in the fields of pathology and gynecology, with implications for the need to decrease mortality from endometrial cancer. Due to many factors, the diagnosis of endometrial precancers and their reliable discrimination from benign mimics remains a difficult area in diagnostic pathology, and among the most frequently encountered in gynecologic pathology. Our understanding of endometrial precancers and their diagnosis has been enhanced by systematic investigations into morphologic criteria, the molecular genetics of endometrial cancer and their precursors, and the validation of individual markers. Despite these refinements, many ambiguous cases are encountered in daily practice, creating diagnostic uncertainty and suboptimal patient management. Recently, an immunohistochemical 3-marker panel consisting of β-catenin, PAX2, and PTEN has been proposed as a diagnostic adjunct. While the panel is useful in routine practice in the majority of cases, these immunostains—like any others—have nuances in their interpretation and require an understanding of normal vs. aberrant patterns of expression. Here, we review criteria for scoring each of the 3 markers and provide a case-based review that serves as a guide for how these markers can be diagnostically helpful in a range of clinical scenarios.