HER-2/neu and p27Kip1 in progression of Fallopian tube carcinoma: an immunohistochemical and array comparative genomic hybridization study.
OBJECTIVE
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.


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.
Nowee
M E
ME
Department of Obstetrics and Gynaecology, VU University Medical Centre, Amsterdam, The Netherlands.
Dorsman
J C
JC
Piek
J M J
JM
Kosma
V M
VM
Hämäläinen
K
K
Verheijen
R H M
RH
van Diest
P J
PJ
D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018450:Disease Progression; D005185:Fallopian Tube Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D023281:Genomics / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D050760:Cyclin-Dependent Kinase Inhibitor p27; D047908:Intracellular Signaling Peptides and Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C436291:CDKN1B protein, human; C508053:ERBB2 protein, human