TOP2A Amplification and Overexpression in Hepatocellular Carcinoma Tissues

Abstract

Hepatocellular carcinoma (HCC) is the leading cause of cancer death in men worldwide owing to limited insights into pathogenesis and unsatisfactory efficacy of current therapies. HER2 and TOP2A genes are coamplified in breast and some other cancers. In this study, we investigated gene aberrations of HER2 and TOP2A and protein expressions of HER2, TOP2A, Ki-67, and p53 in tumor and matched nontumor tissues, as well as their associations with clinicopathological features. Gene aberrations were evaluated by FISH and protein expressions by IHC. Neither HER2 overexpression nor HER2 gene amplification was observed in both tumor tissues and matched nontumor tissues. By contrast, TOP2A overexpression was detected in 72.5% of tumor tissues but not detected in matched nontumor tissues. However, TOP2A gene amplification was not observed in both tumor and matched nontumor tissues. TOP2A overexpression was significantly associated with HCC tumor tissues (P < 0.001), hepatitis B surface antigen (HBsAg) in the serum (P = 0.004), and Ki-67 (P = 0.038) but not with age, tumor size, alpha-fetoprotein, TP53, and copy number of TOP2A gene and chromosome 17 centromere. In conclusion, TOP2A overexpression in HCC was not secondary to gene amplification. In addition, neither HER2 amplification nor overexpression could be used as prognostic and predictive marker in HCC.

Profiles of brain metastases: Prioritization of therapeutic targets

“…19 We did not observe TOP2A amplification in brain metastases, however it is established that TOP2A protein expression is not secondary to gene amplification, which likely explains this discordance. 20 The proteins RRM1, ERCC1 and TS (involved in DNA replication, repair and chemotherapy resistance) were more frequently expressed in metastases than in primary lesions across all three tumor pathologies (NSLC, breast cancer and melanoma). The DNA repair enzyme ERCC1, which plays a role in therapeutic resistance to platinum-based chemotherapy, 21,22 has not been previously documented to be associated with…”

Mechanisms of doxorubicin resistance in hepatocellular carcinoma

“…The situation in HCC, however, appears to be different where TOP2A is increased rather than decreased. In HCC, TOP2A protein level has been shown to be increased independently of gene amplification in 73% of human HCC tumors compared with adjacent non-tumor tissue [40]. It is also overexpressed in several HCC cell lines with acquired doxorubicin resistance [41].…”

Integrated Analysis Revealed Hub Genes in Breast Cancer

“…This nuclear enzyme is mainly related to processes such as chromatid separation, chromosome condensation, and the relief of torsional stress that occurs during DNA transcription and replication. The upregulation of TOP2A was associated with female breast cancer and other cancer types [21]. As a negative regulator of p53, AURKA promotes tumor growth and cell survival.…”