Nassar Aziza, Lawson Diane, Cotsonis George, Cohen Cynthia
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Appl Immunohistochem Mol Morphol. 2008 Mar;16(2):113-20. doi: 10.1097/PAI.0b013e318032ea73.
Survivin is an inhibitor of apoptosis protein that is overexpressed in most human cancers, including breast, but is not expressed in normal tissue. Survivin is associated with more aggressive behavior and decreased survival in a variety of tumor types. It regulates the G2/M phase of the cell cycle by associating with mitotic spindle microtubules, and it directly inhibits caspase-3 and caspase-7 activity. We used a breast cancer tissue microarray to assess survivin and caspase-3 expression in breast cancer and to correlate both markers with proliferation (MIB-1), angiogenesis (CD31), and prognosis.
A breast cancer tissue microarray with a total of 190 1-mm tissue samples (2 from each specimen) were immunostained for survivin, caspase-3, MIB-1, and CD31. The microarray contains 91 cases of breast carcinoma diagnosed at Emory University Hospital between 1992 and 2000, and 4 normal breast tissue controls. Follow-up information was obtained from hospital records and the Winship Cancer Center database.
Eighty-four percent of breast carcinoma showed nuclear survivin expression. Normal breast tissue was immunonegative. Fifty-seven percent and 43% of breast cancer showed reduced and absent caspase-3 expression, respectively. Survivin (nuclear) and caspase (nuclear/cytoplasmic) expression showed significant correlation with histologic grade (P=0.008 and 0.041) and MIB-1 expression (P=0.033 and 0.012). Survivin nuclear expression also correlated significantly with tumor stage (P=0.012) and tended to correlate with estrogen receptor (P=0.050). There was no significant correlation between survivin and caspase expression. Furthermore, there was no correlation of both markers with other clinicopathologic parameters (age, tumor size, histologic type, progesterone receptor, Her-2 neu status, lymph node status), angiogenesis (CD31), or outcome (overall and disease-free survival).
Survivin and caspase-3 expression correlate with poor prognostic parameters (higher histologic grade and high proliferation), but not with outcome, in breast carcinoma patients.
生存素是一种凋亡抑制蛋白，在包括乳腺癌在内的大多数人类癌症中过度表达，但在正常组织中不表达。生存素与多种肿瘤类型中更具侵袭性的行为和生存率降低有关。它通过与有丝分裂纺锤体微管结合来调节细胞周期的G2/M期，并直接抑制半胱天冬酶-3和半胱天冬酶-7的活性。我们使用乳腺癌组织芯片评估乳腺癌中生存素和半胱天冬酶-3的表达，并将这两种标志物与增殖（MIB-1）、血管生成（CD31）及预后相关联。
对一张包含总共190个1毫米组织样本（每个标本2个）的乳腺癌组织芯片进行生存素、半胱天冬酶-3、MIB-1和CD31的免疫染色。该芯片包含1992年至2000年间在埃默里大学医院诊断的91例乳腺癌病例以及4个正常乳腺组织对照。随访信息来自医院记录和温希普癌症中心数据库。
84%的乳腺癌显示核生存素表达。正常乳腺组织免疫阴性。57%和43%的乳腺癌分别显示半胱天冬酶-3表达降低和缺失。生存素（核）和半胱天冬酶（核/胞质）表达与组织学分级（P = 0.008和0.041）及MIB-1表达（P = 0.033和0.012）显著相关。生存素核表达也与肿瘤分期显著相关（P = 0.012），并倾向于与雌激素受体相关（P = 0.050）。生存素和半胱天冬酶表达之间无显著相关性。此外，这两种标志物与其他临床病理参数（年龄、肿瘤大小、组织学类型、孕激素受体、Her-2 neu状态、淋巴结状态）、血管生成（CD31）或结局（总生存和无病生存）均无相关性。
在乳腺癌患者中，生存素和半胱天冬酶-3表达与不良预后参数（更高的组织学分级和高增殖）相关，但与结局无关。
