Immunohistochemical expression of estrogen and progesterone receptors identifies a subset of NSCLCs and correlates with EGFR mutation.
Immunohistochemical expression of estrogen and progesterone receptors identifies a subset of NSCLCs and correlates with EGFR mutation.
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DOI：
10.1158/1078-0432.ccr-09-0033
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发表时间：
2009-09-01
期刊：
影响因子：
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通讯作者：
Wistuba II
中科院分区：
文献类型：
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作者：
Raso MG;Behrens C;Herynk MH;Liu S;Prudkin L;Ozburn NC;Woods DM;Tang X;Mehran RJ;Moran C;Lee JJ;Wistuba II
确定大量非小细胞肺癌（NSCLC）标本中雌激素受体α和β以及孕激素受体蛋白免疫组化表达的频率，并将我们的结果与先前发表的报告中提供不一致结果的一些相同抗体的结果进行比较。使用多种抗体，我们研究了放置在组织微阵列中的317个NSCLC中雌激素受体α和β以及孕激素受体的免疫组织化学表达，并将其表达与患者的临床病理特征以及EGFR突变状态的腺癌相关联。在NSCLC细胞的细胞核和细胞质中检测到雌激素受体α和β;然而，表达频率（细胞核，α为5 - 36%，β为42 - 56%;细胞质：α <1 - 42%，β为20 - 98%）在检测的不同抗体之间存在差异。63%的肿瘤细胞胞核中表达Progr受体。雌激素受体α核表达与腺癌组织学类型、女性性别和从不吸烟史显著相关（P = 0.0048~<0.0001）。多变量分析显示，在NSCLC中，胞浆雌激素受体α表达水平越高，无复发生存率越差（风险比，1.77; 95%可信区间，1.12，2.82; P = 0.015）。在腺癌中，雌激素受体α表达与EGFR突变相关（P = 0.0029至<0.0001）。雌激素受体β和孕激素受体在肺腺癌旁正常上皮中表达，而雌激素受体α不表达。雌激素受体α和β表达可区分具有明确临床病理学和遗传学特征的NSCLC亚群。在肺腺癌中，雌激素受体α表达与EGFR突变相关。
To determine the frequency of estrogen receptor α and β and progesterone receptor protein immunohistochemical expression in a large set of non–small cell lungcarcinoma (NSCLC) specimens and to compare our results with those for some of the same antibodies that have provided inconsistent results in previously published reports. Using multiple antibodies, we investigated the immunohistochemical expression of estrogen receptors α and β and progesterone receptor in 317 NSCLCs placed in tissue microarrays and correlated their expression with patients’ clinicopathologic characteristics and in adenocarcinomas with EGFR mutation status. Estrogen receptors α and β were detected in the nucleus and cytoplasm of NSCLC cells; however, the frequency of expression (nucleus, 5-36% for α and 42-56% for β; cytoplasm: <1-42% for α and 20-98% for β) varied among the different antibodies tested. Progesterone receptor was expressed in the nuclei of malignant cells in 63% of the tumors. Estrogen receptor α nuclear expression significantly correlated with adenocarcinoma histology, female gender, and history of never smoking (P = 0.0048 to <0.0001). In NSCLC, higher cytoplasmic estrogen receptor α expression significantly correlated with worse recurrence-free survival (hazard ratio, 1.77; 95% confidence interval, 1.12, 2.82; P = 0.015) in multivariate analysis. In adenocarcinomas, estrogen receptor α expression correlated with EGFR mutation (P = 0.0029 to <0.0001). Estrogen receptor β and progesterone receptor but not estrogen receptor α expressed in the normal epithelium adjacent to lung adenocarcinomas. Estrogen receptor α and β expression distinguishes a subset of NSCLC that has defined clinicopathologic and genetic features. In lung adenocarcinoma, estrogen receptor α expression correlates with EGFR mutations.