Does polysomy of chromosome 17 have a role in ERBB2 and topoisomerase IIalpha expression? Gene, mRNA and protein expression: a comprehensive analysis.
OBJECTIVE
ERBB2 is an oncogene with prognostic and predictive value. Topoisomerase IIalpha is an enzyme encoding close to the ERBB2 oncogene, that represents a molecular target for anthracyclines. An indirect mechanism of increasing ERBB2 and topoisomerase IIalpha gene copy number is chromosome 17 polysomy. The aim of the present study was to clarify the implication of polysomy 17 in ERBB2 and topoisomerase IIalpha expression. In addition, we assessed the relation of ERBB2 and topoisomerase IIalpha gene dosage to mRNA and protein levels.


METHODS
We selected 83 cases diagnosed as invasive breast cancer. We analysed ERBB2 and topoisomerase IIalpha genes, mRNA and protein by fluorescence in situ hybridisation, real-time reverse-transcription polymerase chain reaction and immunohistochemistry.


RESULTS
We observed a progressive increase in mRNA expression from 0+ to 3+ and also a significant difference in the ERBB2 RNA levels between normal and amplified cases. We found that polysomy of chromosome 17 does not affect the ERBB2 expression and that topoisomerase IIalpha mRNA expression is not related to gene status.


CONCLUSIONS
Our results demonstrate that polysomy of chromosome 17 is not related to ERBB2 expression. Thereby, it is important to use centromeric probes to clearly discriminate between true ERBB2 gene amplification and polysomy of chromosome 17.
Corzo
Cristina
C
Servei d'Oncologia mèdica, Hospital del Mar, IMAS, Barcelona, Spain. E0062@imas.imim.es
Bellosillo
Beatriz
B
Corominas
Josep M
JM
Salido
Marta
M
Coll
Maria Dolors
MD
Serrano
Sergi
S
Albanell
Joan
J
Solé
Francesc
F
Tusquets
Ignacio
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002886:Chromosomes, Human, Pair 17; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*
D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human