Mah Vei, Seligson David B, Li Ai, Márquez Diana C, Wistuba Ignacio I, Elshimali Yahya, Fishbein Michael C, Chia David, Pietras Richard J, Goodglick Lee
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1747, USA.
Cancer Res. 2007 Nov 1;67(21):10484-90. doi: 10.1158/0008-5472.CAN-07-2607.
Estrogen signaling is critical in the progression of tumors that bear estrogen receptors. In most patients with breast cancer, inhibitors that block interactions of estrogen with its receptors or suppress the production of endogenous estrogens are important interventions in the clinic. Recent evidence now suggests that estrogen also contributes to the pathogenesis of non-small cell lung cancer (NSCLC). We used a human lung cancer xenograph model system to analyze the effect of aromatase or estradiol on tumor growth. We further examined the level of protein expression of aromatase in 422 patients with NSCLC using a high-density tissue microarray. Results were confirmed and validated on an independent patient cohort (n = 337). Lower levels of aromatase predicted a greater chance of survival in women 65 years and older. Within this population, the prognostic value of aromatase was greatest in earlier stage lung cancer (stage I/II). In addition, for women with no history of smoking, lower aromatase levels were a strong predictor of survival. Our findings implicate aromatase as an early-stage predictor of survival in some women with NSCLC. We predict that women whose lung cancers have higher levels of aromatase might be good candidates for targeted treatment with aromatase inhibitors.
雌激素信号传导在携带雌激素受体的肿瘤进展中至关重要。在大多数乳腺癌患者中，阻断雌激素与其受体相互作用或抑制内源性雌激素产生的抑制剂是临床上重要的干预措施。最近的证据表明，雌激素也与非小细胞肺癌（NSCLC）的发病机制有关。我们使用人肺癌异种移植模型系统来分析芳香化酶或雌二醇对肿瘤生长的影响。我们进一步使用高密度组织微阵列检测了422例NSCLC患者中芳香化酶的蛋白表达水平。结果在一个独立的患者队列（n = 337）中得到了证实和验证。芳香化酶水平较低预示着65岁及以上女性有更大的生存机会。在这个人群中，芳香化酶的预后价值在早期肺癌（I/II期）中最大。此外，对于无吸烟史的女性，较低的芳香化酶水平是生存的有力预测指标。我们的研究结果表明芳香化酶是一些NSCLC女性患者生存的早期预测指标。我们预测，肺癌中芳香化酶水平较高的女性可能是芳香化酶抑制剂靶向治疗的良好候选者。
