Background Endometrial intraepithelial neoplasia (EIN) is a monoclonal proliferation of endometrial glands that can progress to endometrial carcinoma (EC). Squamous metaplasia (SM) is a common morphologic feature of EIN associated with β-catenin protein alterations. Patients with high-risk endometrial cancer (copy-number high) have frequent TP53 gene mutations and worse outcomes. This study evaluates the prognostic significance of SM, β-catenin, and p53 expression in EIN.
Methods This retrospective study included patients with biopsy-proven EIN, subsequent hysterectomy, and evaluable tissue. Hematoxylin and Eosin (H&E) slides were reviewed to characterize SM; β-catenin and p53 expression were evaluated by immunohistochemistry (IHC).
Results 88 cases met inclusion criteria. On biopsy specimen, 11.4% (10/88) of patients had associated SM, and 2.3% (2/88) had abnormal p53 staining. 80% (8/10) of patients with SM had positive staining for β-catenin versus 2.6% (2/78) of patients lacking SM (p < 0.001) (figure 1). 34.1% (30/88) of patients were diagnosed with EC on subsequent hysterectomy. SM, β-catenin, and p53 expression on biopsy specimen were not correlated with a finding of neoplasia on subsequent hysterectomy (EC or EIN) (p = 0.427, p = 0.104, and p = 0.583, respectively).
Conclusions Our findings confirm the association between SM and β-catenin abnormalities. Although rare, abnormal p53 IHC in EIN is concerning and may represent a precursor to copy-number high EC. Although these findings demonstrate molecular abnormalities within EIN, β-catenin and p53 expression do not reliably predict cancer diagnosis on final hysterectomy specimen.
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