Beg Shaham, Siraj Abdul K, Prabhakaran Sarita, Jehan Zeenath, Ajarim Dahish, Al-Dayel Fouad, Tulbah Asma, Al-Kuraya Khawla S
Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia,
Breast Cancer Res Treat. 2015 Jun;151(3):541-53. doi: 10.1007/s10549-015-3430-3. Epub 2015 May 16.
PTEN is a tumor suppressor that negatively regulates the PI3 K-AKT signaling pathway which is involved in the pathogenesis of many different tumor types and serves as a prognostic marker in breast cancer. However, the significance of the role of PTEN in Middle Eastern ethnic breast cancer has not been explored especially with the fact that breast cancer originating from this ethnic population tend to behave more aggressively than breast cancer in the west. In this study, we analyzed PTEN alteration in a tissue microarray format containing more than 1000 primary breast cancers with clinical follow-up data. Tissue Microarray sections were analyzed for protein expression and copy number change using immunohistochemistry and fluorescence in situ hybridization. Loss of PTEN immunostaining was observed in 77 % of the cases. PTEN loss was significantly associated with large tumor size (p = 0.0030), high grade (p = 0.0281), tumor recurrence (p = 0.0333), and triple-negative breast cancers (p = 0.0086). PTEN loss in triple-negative breast cancers was significantly associated with rapid tumor cell proliferation (p = 0.0396) and poor prognosis (p = 0.0408). PTEN deletion was found only in 60 cases (6.4 %). Loss of PTEN protein expression occurs at high frequency in Middle Eastern breast cancer. PTEN inactivation may potentially lead to an aggressive behavior of tumor cells through stimulation of tumor cell proliferation. Furthermore, PTEN signaling pathway might be used as potential therapeutic target in triple-negative breast cancers since loss of its expression is shown to be significantly associated with this aggressive subtype of breast cancer.
PTEN是一种肿瘤抑制因子,它对PI3K - AKT信号通路起负向调节作用,该信号通路参与多种不同肿瘤类型的发病机制,并作为乳腺癌的预后标志物。然而,PTEN在中东种族乳腺癌中的作用意义尚未得到探索,尤其是考虑到源自该种族人群的乳腺癌往往比西方乳腺癌表现得更具侵袭性。在本研究中,我们以组织芯片形式分析了1000多例原发性乳腺癌的PTEN改变情况,并伴有临床随访数据。使用免疫组织化学和荧光原位杂交技术对组织芯片切片进行蛋白质表达和拷贝数变化分析。在77%的病例中观察到PTEN免疫染色缺失。PTEN缺失与肿瘤体积大(p = 0.0030)、高级别(p = 0.0281)、肿瘤复发(p = 0.0333)以及三阴性乳腺癌(p = 0.0086)显著相关。三阴性乳腺癌中的PTEN缺失与肿瘤细胞快速增殖(p = 0.0396)和预后不良(p = 0.0408)显著相关。仅在60例(6.4%)中发现PTEN缺失。PTEN蛋白表达缺失在中东乳腺癌中高频出现。PTEN失活可能通过刺激肿瘤细胞增殖而潜在地导致肿瘤细胞的侵袭性行为。此外,PTEN信号通路可能作为三阴性乳腺癌的潜在治疗靶点,因为其表达缺失与这种侵袭性乳腺癌亚型显著相关。