Premium
HER‐2/ neu and p27 Kip1 in progression of Fallopian tube carcinoma: an immunohistochemical and array comparative genomic hybridization study
Author(s) -
Nowee M E,
Dorsman J C,
Piek J M J,
Kosma V M,
Hämäläinen K,
Verheijen R H M,
Van Diest P J
Publication year - 2007
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2007.02850.x
Subject(s) - fallopian tube , immunohistochemistry , serous fluid , biology , comparative genomic hybridization , carcinogenesis , in situ hybridization , serous carcinoma , ovarian carcinoma , ovary , pathology , ovarian cancer , medicine , gene expression , cancer , anatomy , endocrinology , gene , genetics , immunology , genome
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.