Williams Daron J, Cohen Cynthia, Darrow Mary, Page Andrew J, Chastain Beth, Adams Amy L
School of Medicine, Emory University, Atlanta, GA, USA.
Appl Immunohistochem Mol Morphol. 2011 Oct;19(5):431-6. doi: 10.1097/PAI.0b013e318206d23d.
The Oncotype DX Recurrence Score (RS) is often used in lymph node-negative, estrogen receptor-positive breast cancer to refine prognosis and direct therapy. Its utility is limited by its cost, proprietary nature, and turnaround time. Markers of proliferation factor heavily into determination of RS. Our aim is to correlate expression of proliferation markers Ki-67 and phosphohistone H3 (PPH3) with RS and other prognostic indicators. Estrogen receptor-positive invasive breast carcinomas from 133 patients with Oncotype DX testing were selected. Representative tumor sections were stained with MIB1, a monoclonal antibody that reacts against Ki-67, and antibody to PPH3. Nuclear staining was quantitated through an automated imaging system. The percentage of positive cells was scored as low (<10%), intermediate (10% to 20%), or high (>20%) for Ki-67, and low (<2%), intermediate (2% to 5%), or high (>5%) for PPH3. Expression of both markers was compared with RS and clinicopathologic parameters including grade, tumor size, lymph node metastasis, and angiolymphatic invasion. Ki-67 and PPH3 expression were both significantly associated with RS (P=0.02 and P=0.027, respectively) and grade (P<0.001 and P=0.002, respectively). Ki-67 expression correlated with angiolymphatic invasion (P=0.01) but not with tumor size or lymph node metastasis; PPH3 expression showed no association with any of these 3 parameters. Expression of proliferation markers Ki-67 and PPH3 by immunohistochemistry is significantly correlated with RS and tumor grade. This observation suggests that immunohistochemical assessment of markers of proliferation may provide useful prognostic information, at lower cost than RS testing.
Oncotype DX复发评分（RS）常用于淋巴结阴性、雌激素受体阳性的乳腺癌，以优化预后并指导治疗。其应用受到成本、专利性质和周转时间的限制。增殖因子的标志物在RS的测定中占很大比重。我们的目的是将增殖标志物Ki-67和磷酸化组蛋白H3（PPH3）的表达与RS及其他预后指标相关联。选取了133例接受Oncotype DX检测的雌激素受体阳性浸润性乳腺癌患者。代表性肿瘤切片用与Ki-67反应的单克隆抗体MIB1和PPH3抗体染色。通过自动成像系统对细胞核染色进行定量。Ki-67阳性细胞百分比分为低（<10%）、中（10%至20%）或高（>20%），PPH3阳性细胞百分比分为低（<2%）、中（2%至5%）或高（>5%）。将两种标志物的表达与RS及临床病理参数进行比较，包括分级、肿瘤大小、淋巴结转移和血管淋巴管浸润。Ki-67和PPH3表达均与RS（分别为P=0.02和P=0.027）及分级（分别为P<0.001和P=0.002）显著相关。Ki-67表达与血管淋巴管浸润相关（P=0.01），但与肿瘤大小或淋巴结转移无关；PPH3表达与这三个参数中的任何一个均无关联。免疫组织化学检测增殖标志物Ki-67和PPH3的表达与RS及肿瘤分级显著相关。这一观察结果表明，增殖标志物的免疫组织化学评估可能提供有用的预后信息，且成本低于RS检测。
