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146 Prognostic significance of histologic squamous metaplasia and immunohistochemical staining patterns of β-catenin and p53 in biopsy-proven endometrial intraepithelial neoplasia
  1. J Wong1,
  2. R Whitaker2,
  3. K Strickland3 and
  4. RA Previs2
  1. 1Duke University School of Medicine, USA
  2. 2Duke University Medical Center, Division of Gynecologic Oncology, USA
  3. 3Duke University Medical Center, Department of Pathology, USA


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).

Abstract 146 Figure 1

Biopsies from patients with EIN were evaluated via H&E. IHC was used to evaluate beta-catenin nuclear staining and p53 overexpression or null expression. Abbreviations: BCAT+, beta-catenin positive expression; WT, wild-type)

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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