Targeting topoisomerase IIa in endometrial adenocarcinoma: a combined chromogenic in situ hybridization and immunohistochemistry study based on tissue microarrays.
Topoisomerase IIa is a nucleic enzyme that affects the topological structure of DNA and also is a target for chemotherapy (ie, anthracyclines). In this study, we coevaluated its protein expression with chromosome 17 and gene status. Using tissue microarrays, 40 cases of sporadic, primary endometrial adenocarcinomas, 5 cases of atypical hyperplasia, and 5 cases of benign hyperplasia were obtained and reembedded into two paraffin blocks with a core diameter of 1 mm. Immunohistochemistry combined with chromogenic in situ hybridization was performed in 2 and 5 microm sections, respectively. Finally using a semiautomated Image Analysis System, we evaluated the levels of Nuclear labeling index of topoisomerase IIa expression. Statistical analysis was performed by SPSS version 11.0 software. The results indicate that chromosome 17 instability (aneuploidy in 7/40 cases) and Topo IIa gene deregulation (amplification in 3/40 and deletion in 1/40 cases) are significant genetic events correlated with biologic behavior in endometrial adenocarcinoma. Because protein overexpression was observed in a significant proportion of the tumors (18/40), detection of the specific gene deregulation mechanism is a crucial process for application of targeted chemotherapies, which are characterized by different levels of cardiotoxicity and other serious effects.
Tsiambas
E
E
Department of Cytopathology, Evangelismos Hospital, 18B Symis Str., Ag Paraskevi, pc 15341 Athens, Greece. tsiambasecyto@yahoo.gr
Alexopoulou
D
D
Lambropoulou
S
S
Gerontopoulos
K
K
Karakitsos
P
P
Karameris
A
A
D000230:Adenocarcinoma / Q000201:enzymology*; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis / Q000378:metabolism*; D002863:Chromogenic Compounds / Q000494:pharmacology; D043171:Chromosomal Instability; D002886:Chromosomes, Human, Pair 17 / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D004714:Endometrial Hyperplasia / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D040081:Protein Array Analysis / Q000379:methods; D046888:Tissue Array Analysis / Q000379:methods*
D000951:Antigens, Neoplasm; D002863:Chromogenic Compounds; D004268:DNA-Binding Proteins; D004250:DNA Topoisomerases, Type II