Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Lung Cancer. 2012 Jan;75(1):24-9. doi: 10.1016/j.lungcan.2011.05.015.
Bronchioloalveolar carcinoma (BAC) pattern is often seen at the margin of invasive adenocarcinomas. We investigated EGFR signaling abnormalities involved in the progression of adenocarcinoma. Fifty tumors were obtained from patients who underwent surgery for lung adenocarcinoma seen as dense areas in ground glass opacity on computed tomography. Six, 18, and 26 tumors <1cm, 1-2 cm, and ≥2 cm in diameter, respectively, were analyzed. Of the 24 tumors ≤2 cm in diameter, nine were preinvasive and 15 were invasive. EGFR, pAKT, and pMAPK were overexpressed in the center of the adenocarcinoma compared to the BAC component (p<0.01) by immunohistochemistry, while pSTAT3 expression was reversed (p=0.017). In the tumors ≤2 cm in diameter, pSTAT3 expression in the central area was higher in preinvasive tumors than in invasive tumors (p=0.005). pSTAT3 was identified in the BAC component of 88% of the EGFR mutant (n=17) and 82% of the wild-type tumors (n=33). Transgenic mice expressing delE748-A752 EGFR and two lung cancer cell lines (PC-9 mutant and A549 wild-type EGFR) were also investigated. In transgenic mice, pSTAT3 was overexpressed in the BAC component around the adenocarcinoma center. Two lung cancer cell lines that overexpressed pSTAT3 were equally sensitive to a JAK2/STAT3 inhibitor (JSI-124). The role of STAT3 in the progression of adenocarcinoma should be further pursued.
细支气管肺泡癌（BAC）模式通常见于浸润性腺癌的边缘。我们研究了涉及腺癌进展的 EGFR 信号异常。从因 CT 显示毛玻璃密度阴影而接受肺癌手术的患者中获得了 50 个肿瘤。分别分析了直径<1cm、1-2cm 和≥2cm 的 6、18 和 26 个肿瘤。在直径≤2cm 的 24 个肿瘤中，9 个为前驱病变，15 个为浸润性肿瘤。免疫组化显示，与 BAC 成分相比，腺癌中心的 EGFR、pAKT 和 pMAPK 表达过度（p<0.01），而 pSTAT3 表达相反（p=0.017）。在直径≤2cm 的肿瘤中，前驱病变中心区域的 pSTAT3 表达高于浸润性肿瘤（p=0.005）。在 EGFR 突变（n=17）和野生型肿瘤（n=33）的 88%和 82%的肿瘤中，都在 BAC 成分中发现了 pSTAT3。还研究了表达 delE748-A752 EGFR 的转基因小鼠和两种肺癌细胞系（PC-9 突变型和 A549 野生型 EGFR）。在转基因小鼠中，pSTAT3 在腺癌中心周围的 BAC 成分中过度表达。两种过度表达 pSTAT3 的肺癌细胞系对 JAK2/STAT3 抑制剂（JSI-124）同样敏感。STAT3 在腺癌进展中的作用值得进一步研究。
