IPATIMUP: Institute of Molecular Pathology and Immunology of the University of Porto, University of Porto, Rua Dr Roberto Frias s/n, 4200-465, Porto, Portugal.
Virchows Arch. 2010 Mar;456(3):235-43. doi: 10.1007/s00428-010-0881-0. Epub 2010 Feb 4.
Class IA phosphoinositide-3'-kinases (PI3Ks) regulate many cellular processes. Despite a clear implication of PI3K in cancer, the involvement of each of its isoforms namely p110alpha and p110beta in the development of breast cancer remains elusive. Until recently, the spotlight was given to the alpha subunit; however, the p110beta isoform has now emerged as an interesting target as well. In order to determine the importance of both these subunits in breast cancer, we aimed to study the expression of p110alpha and p110beta in a series of invasive breast carcinomas. We constructed tissue microarrays from 315 invasive breast carcinomas and performed immunohistochemistry for p110alpha and beta, correlating the expression patterns with clinicopathological parameters. Furthermore, overall survival was analysed through Kaplan-Meier survival curves and Cox regression. We found that p110 subunits are expressed in 23.8% of invasive breast carcinomas, of which 11.8% express p110alpha and 15.2% p110beta. The p110alpha positive tumours correlated with hormone receptor (HR) expression, and were not associated with overall survival. The membrane expression of p110beta was associated with worse prognosis. This was due to its link to HER2-overexpression, lower age of onset, higher grade, lymph node involvement, distant metastasis and was inversely associated with HR status. Furthermore, p110beta expression was associated with worse overall survival. Importantly our results indicate a role for the beta subunit in the development/progression of HER2-overexpressing tumours, highlighting possible therapeutic associations between HER2 and p110beta inhibitors.
IA 类磷酸肌醇-3-激酶（PI3Ks）调节许多细胞过程。尽管 PI3K 明显与癌症有关，但每个同工酶（即 p110alpha 和 p110beta）在乳腺癌的发展中的作用仍不清楚。直到最近，焦点才放在 alpha 亚基上；然而，p110beta 同工酶现在也成为了一个有趣的靶点。为了确定这两个亚基在乳腺癌中的重要性，我们旨在研究一系列浸润性乳腺癌中 p110alpha 和 p110beta 的表达。我们从 315 例浸润性乳腺癌中构建了组织微阵列，并进行了 p110alpha 和 beta 的免疫组织化学染色，将表达模式与临床病理参数相关联。此外，通过 Kaplan-Meier 生存曲线和 Cox 回归分析进行了总生存分析。我们发现，p110 亚基在 23.8%的浸润性乳腺癌中表达，其中 11.8%表达 p110alpha，15.2%表达 p110beta。p110alpha 阳性肿瘤与激素受体（HR）表达相关，与总生存无关。p110beta 的膜表达与预后不良相关。这是由于它与 HER2 过表达、发病年龄较低、分级较高、淋巴结受累、远处转移有关，并且与 HR 状态呈负相关。此外，p110beta 的表达与总生存不良相关。重要的是，我们的结果表明 beta 亚基在 HER2 过表达肿瘤的发展/进展中起作用，突出了 HER2 和 p110beta 抑制剂之间可能的治疗关联。
