Pelosi Giuseppe, Pasini Felice, Fraggetta Filippo, Pastorino Ugo, Iannucci Antonio, Maisonneuve Patrick, Arrigoni Gianluigi, De Manzoni Giovanni, Bresaola Enrica, Viale Giuseppe
Department of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan School of Medicine, Via G. Ripamonti, 435, I-20141 Milan, Italy.
Lung Cancer. 2003 Nov;42(2):203-13. doi: 10.1016/s0169-5002(03)00294-0.
Immunoreactivity for fascin, an actin-bundling protein related to cell motility, has been reported in breast, ovary, pancreas, skin, and non-small cell carcinomas, and associated with more advanced disease stage and poorer prognosis. Data on pulmonary neuroendocrine (NE) tumors, however, are lacking. We evaluated the expression of fascin by immunohistochemistry--using two different monoclonal antibodies--in surgical specimens of pulmonary NE tumors of all the diverse histological types from 128 consecutive patients recruited between 1987 and 2001, and investigated its relationship with the presence of lymph node metastases. Overall, fascin immunoreactivity was detected in 5% of 38 typical carcinoids (TC), 35% of 23 atypical carcinoids (AC), 83% of 40 large-cell neuroendocrine carcinomas (LCNEC), and 100% of 27 small-cell lung carcinomas (SCLC) (P<0.001), Normal NE cells or hyperplastic NE tumorlets were consistently unreactive. No statistically significant differences in fascin immunoreactivity were found between the two antibodies. In TC and AC but not high-grade NE tumors, fascin immunoreactivity closely correlated with the occurrence of lymph node metastases, the pN class and the number of involved lymph nodes (P<0.001). It was also significantly associated with an increased proliferative activity (Ki-67 labeling index >5%) (P=0.020), and with either down-regulation or altered subcellular compartmentalization of E-cadherin (P<0.001) and CD99 (P=0.030), two cell adhesion complexes in pulmonary NE tumors. At multivariate analysis, only fascin emerged as an independent predictor of lymph node metastases in this tumor group (HR 30.28; 95% confidence intervals: 1.59-574.49; P=0.023). This study indicates that fascin immunoreactivity may identify subsets of pulmonary carcinoid patients with different metastatic potential to regional lymph nodes. Targeting the fascin pathway could be a novel therapeutic strategy of pulmonary carcinoids.
肌动蛋白成束蛋白fascin与细胞运动相关，已有报道称其在乳腺癌、卵巢癌、胰腺癌、皮肤癌和非小细胞癌中具有免疫反应性，并与疾病进展更严重及预后更差相关。然而，关于肺神经内分泌（NE）肿瘤的数据却很缺乏。我们通过免疫组织化学方法——使用两种不同的单克隆抗体——评估了1987年至2001年间连续招募的128例患者的各种组织学类型的肺NE肿瘤手术标本中fascin的表达，并研究了其与淋巴结转移的关系。总体而言，在38例典型类癌（TC）中有5%检测到fascin免疫反应性，23例非典型类癌（AC）中有35%，40例大细胞神经内分泌癌（LCNEC）中有83%，27例小细胞肺癌（SCLC）中有100%（P<0.001），正常NE细胞或增生性NE微瘤始终无反应。两种抗体之间在fascin免疫反应性方面未发现统计学上的显著差异。在TC和AC中，但在高级别NE肿瘤中未发现，fascin免疫反应性与淋巴结转移的发生、pN分级及受累淋巴结数量密切相关（P<0.001）。它还与增殖活性增加（Ki-67标记指数>5%）显著相关（P=0.020），并与肺NE肿瘤中的两种细胞粘附复合物E-钙粘蛋白（P<0.001）和CD99（P=0.030）的下调或亚细胞定位改变相关。在多变量分析中，只有fascin在该肿瘤组中成为淋巴结转移的独立预测因子（风险比30.28；95%置信区间：1.59 - 574.49；P=0.023）。本研究表明，fascin免疫反应性可能识别出肺类癌患者中具有不同区域淋巴结转移潜能的亚组。靶向fascin途径可能是肺类癌的一种新的治疗策略。
