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      Pathologic features of aggressive vulvar carcinoma are associated with an epithelial-mesenchymal transition

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          Abstract

          Factors contributing to aggressive behavior in vulvar squamous cell carcinoma (vSCC) are poorly defined; however, a recent study has shown that vSCCs with an infiltrative pattern of invasion and fibromyxoid stroma are associated with worse outcomes than tumors with a pushing or nested pattern of invasion and lymphoplasmacytic stroma. Epithelial-mesenchymal transition (EMT) has been associated with tumor progression in a number of malignancies, and this study proposes that EMT contributes to tumor aggressiveness in this subset of vSCC. Immunohistochemistry was used to detect nuclear localization of β-catenin, loss of E-cadherin, and presence of vimentin in 58 cases of vSCC. The association of these phenotypic changes with pathologic features and clinical outcomes was tested using Fisher’s exact and χ 2 analyses (significance at p ≤0.05). EMT-associated features were identified in 45 of 58 cases (78%) with 28 cases exhibiting more than one feature. Nuclear β-catenin and presence of vimentin were significantly more likely to occur in tumors with an infiltrative pattern of invasion or a fibromyxoid stromal response. Loss of E-cadherin was significantly associated with an infiltrative pattern, but not a fibromyxoid stroma. Risk for tumor recurrence was significantly increased in tumors with nuclear localization of β-catenin alone or in tumors displaying multiple EMT-associated features. These results suggest that the development of an EMT may be a mechanism by which infiltrative vulvar tumors with a fibromyxoid stromal response behave more aggressively and convey worse outcomes than tumors that do not exhibit these pathologic features.

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          Author and article information

          Journal
          9421547
          4136
          Hum Pathol
          Hum. Pathol.
          Human pathology
          0046-8177
          1532-8392
          25 June 2016
          18 June 2016
          October 2016
          01 October 2017
          : 56
          : 22-30
          Affiliations
          [1 ]Department of Pathology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR, 72205, U.S.A
          [2 ]Department of Biostatistics, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR, 72205, U.S.A
          Author notes
          Corresponding Author: Charles M. Quick, MD, University of Arkansas for Medical Sciences, Department of Pathology, 4301 West Markham Street, Slot 517, Little Rock, Arkansas, 72205, Office: (501) 526-5251, Fax: (501) 686-6531, QuickCharlesM@ 123456uams.edu
          [*]

          These authors contributed equally to this work.

          Article
          PMC5021565 PMC5021565 5021565 nihpa796740
          10.1016/j.humpath.2016.05.020
          5021565
          27327194
          59b662b5-5113-43fb-a222-a9de4727348c
          History
          Categories
          Article

          vulva,carcinoma,EMT,invasive pattern,stromal response
          vulva, carcinoma, EMT, invasive pattern, stromal response

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