Xia Wei-Ya, Lien Huang-Chun, Wang Shao-Chun, Pan Yung, Sahin Aysegul, Kuo Yau-Hung, Chang King-Jeng, Zhou Xin, Wang Hongying, Yu Zhengming, Hortobagyi Gabriel, Shi Dar-Ren, Hung Mien-Chie
Department of Molecular and Cellular Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Breast Cancer Res Treat. 2006 Aug;98(3):295-301. doi: 10.1007/s10549-006-9162-7. Epub 2006 Jun 3.
The ETS protein PEA3 functions as a transcription factor to regulate gene expression. Although members of the ETS family have been reported to be involved in tumor progression, ectopic expression of PEA3 has been shown to suppress tumor formation. Despite several studies demonstrated frequent expression of PEA3 and its high association with HER-2/neu and have suggested a potential role of PEA3 in breast cancer, contradictory result has shown that the PEA3 was associated with better survival rate in breast cancer. In the current study, we address this discrepancy by examining the expression of PEA3 and HER-2/neu on 289 archived breast cancer tumor tissues and their correlation with clinicopathologic factors and prognosis. The staining of PEA3 was further validated by in situ hybridization for PEA3 mRNA. We found PEA3 was positive in 22.2% (64/289) of all cases and only 25.6% (21/82) of HER-2/neu-overexpressing cases showed co-expression of PEA3. In contrast to HER-2/neu, PEA3 expression was not correlated with prognosis or major clinicopathologic factors, except for a negative correlation with lymphovascular permeation ( p=0.007). This study demonstrates that PEA3 expression is not correlated with HER-2/neu expression in breast cancer tumor tissues, nor is it associated with adverse clinicopathologic factors or prognosis.
ETS蛋白PEA3作为一种转录因子发挥作用以调控基因表达。尽管已有报道称ETS家族成员参与肿瘤进展,但PEA3的异位表达已被证明可抑制肿瘤形成。尽管多项研究表明PEA3表达频繁且与HER-2/neu高度相关,并提示PEA3在乳腺癌中可能发挥作用,但相互矛盾的结果显示PEA3与乳腺癌更好的生存率相关。在本研究中,我们通过检测289例存档乳腺癌肿瘤组织中PEA3和HER-2/neu的表达及其与临床病理因素和预后的相关性来解决这一差异。通过PEA3 mRNA的原位杂交进一步验证了PEA3的染色情况。我们发现,在所有病例中,PEA3阳性率为22.2%(64/289),在HER-2/neu过表达的病例中,只有25.6%(21/82)显示PEA3共表达。与HER-2/neu不同, PEA3表达与预后或主要临床病理因素无关,仅与淋巴管浸润呈负相关(p = 0.007)。本研究表明,在乳腺癌肿瘤组织中,PEA3表达与HER-2/neu表达无关,也与不良临床病理因素或预后无关。