AIMS: To determine expression of p53, HER-2/neu and p27(Kip1) in serous Fallopian tube carcinoma (FTC) in relation to stage and grade, and to investigate DNA copy number changes of HER-2 and P27KIP1 as a potential mechanism of altered expression status. METHODS AND RESULTS: Immunohistochemistry was performed on 28 serous FTCs and 10 normal Fallopian tubes. p53 protein accumulated and p27(Kip1) was down-regulated significantly in early-stage FTCs compared with normal Fallopian tubes. HER-2/neu overexpression was absent in normal Fallopian tubes and in all stage I FTCs (n = 6) but present in 57% (12/21) of advanced-stage FTCs. No differences in expression between grade 2 and 3 tumours were detected. HER-2 gain/amplification was found by array comparative genomic hybridization in 23% (3/13) of analysed FTCs and all showed overexpression. HER-2/neu overexpression also occurred without DNA copy number changes in three other cases. For p27(Kip1), expression and DNA copy number were unrelated. CONCLUSIONS: p53 accumulation and p27(Kip1) down-regulation seem to be early events in Fallopian tube carcinogenesis. HER-2/neu showed overexpression, caused by gain/amplification in 50%, and may be involved in progression of FTC. These data contribute to a better understanding of the molecular carcinogenesis of FTC and to possible new therapeutic approaches.
AIMS: To determine expression of p53, HER-2/neu and p27(Kip1) in serous Fallopian tube carcinoma (FTC) in relation to stage and grade, and to investigate DNA copy number changes of HER-2 and P27KIP1 as a potential mechanism of altered expression status. METHODS AND RESULTS: Immunohistochemistry was performed on 28 serous FTCs and 10 normal Fallopian tubes. p53 protein accumulated and p27(Kip1) was down-regulated significantly in early-stage FTCs compared with normal Fallopian tubes. HER-2/neu overexpression was absent in normal Fallopian tubes and in all stage I FTCs (n = 6) but present in 57% (12/21) of advanced-stage FTCs. No differences in expression between grade 2 and 3 tumours were detected. HER-2 gain/amplification was found by array comparative genomic hybridization in 23% (3/13) of analysed FTCs and all showed overexpression. HER-2/neu overexpression also occurred without DNA copy number changes in three other cases. For p27(Kip1), expression and DNA copy number were unrelated. CONCLUSIONS:p53 accumulation and p27(Kip1) down-regulation seem to be early events in Fallopian tube carcinogenesis. HER-2/neu showed overexpression, caused by gain/amplification in 50%, and may be involved in progression of FTC. These data contribute to a better understanding of the molecular carcinogenesis of FTC and to possible new therapeutic approaches.
Authors: Henry D Reyes; Kristina W Thiel; Matthew J Carlson; Xiangbing Meng; Shujie Yang; Jean-Marie Stephan; Kimberly K Leslie Journal: Mol Diagn Ther Date: 2014-04 Impact factor: 4.074
Authors: Russell Vang; Kala Visvanathan; Amy Gross; Emily Maambo; Mamta Gupta; Elisabetta Kuhn; Rose Fanghong Li; Brigitte M Ronnett; Jeffrey D Seidman; Anna Yemelyanova; Ie-Ming Shih; Patricia A Shaw; Robert A Soslow; Robert J Kurman Journal: Int J Gynecol Pathol Date: 2012-05 Impact factor: 2.762