HER2/Topoisomerase IIa co-amplified breast adenocarcinoma "mirror" cases with different Topoisomerase IIa expression patterns.

Concerning breast adenocarcinomas, critical genes -including HER2/neu, Topoisomerase IIa (Topo IIa) and estrogen/progesterone receptorsare frequently altered, affecting the biological behavior of the neoplasm and also the response rates to specific targeted or chemotherapeutic agents [1]. Interestingly, HER2 and Topo IIa genes share the same Chr 17 locus (band 17q12-21) and for this reason they are frequently co-amplified (~40-90%) demonstrating different protein expression. Additionally, Chr 17 polysomy combined or not with these genes’ amplification seems to be to an independent predictor for anthracycline (a Topo IIa inhibitor) response -as adjuvant chemotherapyin sub groups of breast cancer cases [2]. In contrast to this, Topo IIa gene deletion is associated with poor prognosis and an aggressive phenotype in the corresponding patients [3]. Two female patients, a 39-year-old and a 46-year-old, were diagnosed with breast cancer in 417 VA Hospital. Surgical resection was performed and pathology showed breast ductal adenocarcinoma grade I and II, respectively based on WHO breast tumor classification. Fluoresence in situ hybridization (FISH) with a triple color signal (HER2/TopoIIa/ CEP17) and immunohistochemical (IHC) analyses were performed in the corresponding tissue sections. Evaluation of gene/protein expression patterns was based on ASCO/ACAP guidelines 2013 [4]. In both of the examined cases, FISH detected combined HER2 & Topo IIa gene amplification. In the first case IHC analysis demonstrated a HER2 score 3+ with a low Topo IIa expression, whereas the second case showed a HER2 score 2+ with high Topo IIa protein expression (Figure 1). Chr 17 demonstrated a normal diploid pattern in both of them. Concerning the oncological approach of the cases, trastuzumab (anti-HER2 monoclonal antibody) and anthracycline (doxorubicin) based chemotherapy was administered. A 2-year follow up showed high response rates for the monoclonal antibody in both of the cases, but differences in anthracycline response were also reported. The first patient did not benefited after the regimen implementation and the chemotherapy was dropped. Topoisomerase IIa gene alterations -including amplification and deletionlead to different protein expresHER2/Topoisomerase IIa co-amplified breast adenocarcinoma “mirror” cases with different Topoisomerase IIa expression patterns