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Nuclear Localization of β‐catenin Associates EMT with Aggressive Vulvar Squamous Cell Carcinoma
Author(s) -
Holthoff E,
Jeffus S,
Kelly T,
Quick C,
Post S
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.147.3
Subject(s) - immunostaining , pathology , staining , catenin , biology , immunohistochemistry , medicine , wnt signaling pathway , signal transduction , microbiology and biotechnology
Nuclear localization of β‐catenin in epithelial cells characterizes the epithelial‐mesenchymal transition (EMT) and is associated with tumor progression in numerous malignancies. Factors that contribute to aggressive behavior in vulvar squamous cell carcinoma (vSCC) are poorly defined; however, studies have shown that vSCC with an infiltrative pattern of invasion are associated with worse outcomes compared to those with nested/pushing patterns of invasion. This study proposes that infiltrative vSCC may acquire increased aggressive behavior through EMT‐like changes reflected by nuclear localization of β‐catenin. Immunostaining patterns of β‐catenin were analyzed in 30 cases of vSCC: 10 cases with infiltrative pattern of invasion, 10 with nested/pushing pattern of invasion, and 10 with a “mixed” invasive pattern. Stained tumor sections were analyzed for nuclear localization or membranous staining of β‐catenin. A staining pattern was defined as predominant when present in >75% of tumor cells. Predominant nuclear localization of β‐catenin was observed in 8 (80%) of the infiltrative tumors, compared to only 3 (30%) of the pushing/nested tumors. In contrast, membranous staining predominated in 5 (50%) of the nested/pushing tumors compared to only 1 (10%) of the infiltrative tumors. Both membranous staining and nuclear localization of β‐catenin was observed in 7 (70%) of the mixed tumors. Importantly, in 6 of the 7 mixed tumors (85%), β‐catenin showed membranous staining in the pushing regions and nuclear localization in the infiltrative regions. Our results show that nuclear localization of β‐catenin is highly associated with an infiltrative pattern of invasion in vSCC, suggesting that development of an epithelial‐mesenchymal transition drives the more aggressive behavior in this subset of tumors.