218 Modeling E-Cadherin Expression Status to Predict Bladder Cancer Progression. (11th January 2018)

• Record Type: Journal Article
• Authors: Gupta, Sounak; Cheville, John; Hansel, Donna
• Is Part Of: American journal of clinical pathology. Volume 149(2018)Supplement 1
• Page Start: S93
• Page End: S93
• Publication Date: 2018-01-11
• Subjects: Diagnosis, Laboratory -- Periodicals; Pathology -- Periodicals; 616.07
• DOI: 10.1093/ajcp/aqx123.217
• Languages: English
• ISSNs: 0002-9173

Abstract

Abstract: Objectives: The majority of patients with bladder cancer present with noninvasive disease (low-grade [NILG] and high-grade [NIHG] papillary: carcinoma in situ [CIS]). Progression to muscle-invasive disease significantly reduces five-year survival rates to 63% (SEER), and an important component of disease progression involves epithelial to mesenchymal transition. We therefore investigated E-cadherin expression and localization in the progression to pT1 and pT2 invasive disease. Methods: This retrospective study design involved 60 patients who had an initial diagnosis of pTa (NILG n = 7; NIHG n = 10), pTis (n = 30), and pT1 disease (n = 13), with a mean follow-up of 96 months to assess for progression. Initial biopsies diagnosed as pTa/pTis/pT1 disease were immunostained for E-cadherin, and membrane staining was evaluated for focal or extensive loss. Results: Of the 47 patients with non-invasive disease, we identified 20 progressors that included 0 NILG (0%), four NIHG (9%), and 16 patients with CIS (34%). Mean follow-up in these three cohorts was 93, 87, and 119 months, respectively. Loss of E-cadherin was identified in a small subset of these patients and included one of four NIHG progressors (25%), five of 16 CIS progressors (31%), and two of five pT1 progressors (40%). When comparing to the nonprogressor cohort, E-cadherin loss unexpectedly appeared equivalent to or more prevalent than the progressor cohort [one of six NIHG (17%), eight of 14 CIS (57%), and six of eight pT1 (75%) patients]. This data suggest that E-cadherin loss is not directly correlated to stage progression and outcomes, but rather related more closely to clinical stage at the time of diagnosis. Conclusion: E-cadherin loss occurs with increasing frequency in high-grade bladder cancers of increasing stage. Our results suggest that E-cadherin loss is intrinsic to more advanced cancers and may reflect possible transition to an epithelial-mesenchymal phenotype and/or increased cell dyscohesion in the context of invasion.