Altered expression pattern of topoisomerase IIalpha in ovarian tumor epithelial and stromal cells after platinum-based chemotherapy.
OBJECTIVE
The aim of this study was to evaluate the expression of topoisomerase IIalpha (TOP2A) in epithelial and stromal cells of ovarian cancer.


METHODS
TOP2A expression was analyzed prospectively in normal and tumor epithelial and adjacent stromal cells using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) after laser microdissection (n = 38), RNA in situ hybridization (n = 13), and immunohistochemistry (n = 69).


RESULTS
TOP2A mRNA was detected by RNA in situ hybridization in all ovarian cancer samples, with stronger hybridization signals in tumor epithelial cells compared to adjacent stromal cells. The same expression pattern was found by immunohistochemistry (P = .0001). Very interestingly, specific change was found in recurrent ovarian cancer after platinum-based chemotherapy: TOP2A expression decreased in tumor epithelial cells of recurrent ovarian cancer compared to primary ovarian cancer (P = .056), whereas it increased in tumor-adjacent stromal cells in carboplatin-treated recurrent tumors compared to primary ovarian cancer (P = .023).


CONCLUSIONS
TOP2A mRNA and protein expression in ovarian cancer exhibits specific patterns in tumor epithelial and adjacent stromal cells, which are differentially modulated after platinum-based chemotherapy. These data support the recently discovered importance of the stromal compartment in tumor progression and suggest that tumor stromal cells might be relevant to the development of chemotherapy resistance in ovarian cancer.
Chekerov
Radoslav
R
Department of Obstetrics and Gynecology, Charité University Hospital, Campus Virchow, Berlin, Germany.
Klaman
Irina
I
Zafrakas
Menelaos
M
Könsgen
Dominique
D
Mustea
Alexander
A
Petschke
Beate
B
Lichtenegger
Werner
W
Sehouli
Jalid
J
Dahl
Edgar
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007834:Lasers; D042282:Microdissection; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human