BACKGROUND: Sarcomatoid renal cell carcinomas (SRCC) are composed of two cell populations, a sarcomatous component (SC) and a carcinomatous component (CC). SRCC are particularly aggressive and often present at an advanced stage at diagnosis. Epithelial-mesenchymal transition (EMT) has been proposed as a mechanism for the development of SC from CC. AIMS AND METHODS: E- to N-cadherin switching, localisation of β-catenin, and expression of Snail and secreted protein acidic and rich in cysteine (SPARC) (markers of EMT) were studied to determine whether SRCC is an example of EMT. Expression of these markers was analysed by immunohistochemistry on 21 cases of SRCC that had both SC and CC and scored according to intensity and extent. RESULTS: E-cadherin expression was decreased in SC (Wilcoxon signed-rank test, p=0.0004) while N-cadherin expression was high in both components (p=0.46). Membranous β-catenin expression was decreased in SC (p<0.0001) while cytoplasmic expression was increased (p=0.0002). Snail and SPARC had higher expression in SC (p=0.002 and p<0.0001, respectively). When the scores were dichotomised into low and high expression levels, the results using McNemar's test substantiated the above results. CONCLUSIONS: E- to N-cadherin switching, dissociation of β-catenin from the membrane, and increased expression of Snail and SPARC in SC indicate that SRCC is an example of EMT. High expression of N-cadherin and Snail in CC suggest early involvement in initiating EMT. Once EMT is established, loss of E-cadherin, release of β-catenin into the cytoplasm, and expression of SPARC correspond with mesenchymal phenotypic expression.
BACKGROUND:Sarcomatoid renal cell carcinomas (SRCC) are composed of two cell populations, a sarcomatous component (SC) and a carcinomatous component (CC). SRCC are particularly aggressive and often present at an advanced stage at diagnosis. Epithelial-mesenchymal transition (EMT) has been proposed as a mechanism for the development of SC from CC. AIMS AND METHODS: E- to N-cadherin switching, localisation of β-catenin, and expression of Snail and secreted protein acidic and rich in cysteine (SPARC) (markers of EMT) were studied to determine whether SRCC is an example of EMT. Expression of these markers was analysed by immunohistochemistry on 21 cases of SRCC that had both SC and CC and scored according to intensity and extent. RESULTS:E-cadherin expression was decreased in SC (Wilcoxon signed-rank test, p=0.0004) while N-cadherin expression was high in both components (p=0.46). Membranous β-catenin expression was decreased in SC (p<0.0001) while cytoplasmic expression was increased (p=0.0002). Snail and SPARC had higher expression in SC (p=0.002 and p<0.0001, respectively). When the scores were dichotomised into low and high expression levels, the results using McNemar's test substantiated the above results. CONCLUSIONS: E- to N-cadherin switching, dissociation of β-catenin from the membrane, and increased expression of Snail and SPARC in SC indicate that SRCC is an example of EMT. High expression of N-cadherin and Snail in CC suggest early involvement in initiating EMT. Once EMT is established, loss of E-cadherin, release of β-catenin into the cytoplasm, and expression of SPARC correspond with mesenchymal phenotypic expression.
Authors: Jiaqi Mi; Erika Hooker; Steven Balog; Hong Zeng; Daniel T Johnson; Yongfeng He; Eun-Jeong Yu; Huiqing Wu; Vien Le; Dong-Hoon Lee; Joseph Aldahl; Mark L Gonzalgo; Zijie Sun Journal: J Biol Chem Date: 2018-11-06 Impact factor: 5.157
Authors: Sumanta K Pal; Jeremy O Jones; Courtney Carmichael; Junmi Saikia; Joanne Hsu; Xueli Liu; Robert A Figlin; Przemyslaw Twardowski; Clayton Lau Journal: Urol Oncol Date: 2012-05-17 Impact factor: 3.498
Authors: Sumanta K Pal; Miaoling He; Tommy Tong; Huiqing Wu; Xueli Liu; Clayton Lau; Jin-Hui Wang; Charles Warden; Xiwei Wu; Sabina Signoretti; Toni K Choueiri; Jose A Karam; Jeremy O Jones Journal: Mol Cancer Res Date: 2014-09-02 Impact factor: 5.852
Authors: Mark Bi; Siming Zhao; Jonathan W Said; Maria J Merino; Adebowale J Adeniran; Zuoquan Xie; Cayce B Nawaf; Jaehyuk Choi; Arie S Belldegrun; Allan J Pantuck; Harriet M Kluger; Kaya Bilgüvar; Richard P Lifton; Brian Shuch Journal: Proc Natl Acad Sci U S A Date: 2016-02-10 Impact factor: 11.205