Department of Pathology, IRCCS Arcispedale Santa Maria Nuova, viale Risorgimento, 80 42100, Reggio Emilia, Italy; Section of Pathologic Anatomy, University of Modena and Reggio Emilia, Modena, Italy.
Unit of Pathology San Camillo Hospital, Malpighi Pavillon, Rome, Italy.
Semin Diagn Pathol. 2013 Nov;30(4):298-312. doi: 10.1053/j.semdp.2013.11.007. Epub 2013 Nov 13.
Non-small-cell lung cancer (NSCLC) subtyping has recently been a key factor in determining patient management with novel drugs. In addition, the identification of distinct oncogenic driver mutations frequently associated with NSCLC histotype and coupled to the clinical responses to targeted therapies have revolutionized the impact of histologic type and molecular biomarkers in lung cancer. Several molecular alterations involving different genes (EGFR, KRAS, ALK, BRAF, and HER2) seem to have a remarkable predilection for adenocarcinoma and specific inhibitors of EGFR and ALK are now available for patients with adenocarcinoma harboring the relevant gene alterations. The efficacy of histology-based and molecular-targeted therapies had a deep impact in (1) re-defining classification of lung cancer (particularly adenocarcinomas) and (2) routine clinical practice of pathologists involved in optimization of handling of tissue samples in order to guarantee NSCLC subtyping with the help of immunohistochemistry and adequately preserve tumor cells for molecular analysis. In agreement with the modern multidisciplinary approach to lung cancer, we reviewed here the diagnostic and predictive value of molecular biomarkers according to the clinical, pathologic, and molecular biologist viewpoints.
非小细胞肺癌 (NSCLC) 亚分型最近已成为确定新型药物治疗患者管理的关键因素。此外，与 NSCLC 组织类型相关的独特致癌驱动基因突变的鉴定以及与靶向治疗的临床反应相结合，彻底改变了组织学类型和分子生物标志物在肺癌中的作用。涉及不同基因（EGFR、KRAS、ALK、BRAF 和 HER2）的几种分子改变似乎对腺癌有明显的偏好，并且现在有针对携带相关基因突变的腺癌患者的 EGFR 和 ALK 特异性抑制剂。基于组织学和分子靶向治疗的疗效对以下方面产生了深远影响：(1) 重新定义肺癌（特别是腺癌）的分类；(2) 参与优化组织样本处理的病理学家的常规临床实践，以帮助免疫组织化学进行 NSCLC 亚分型，并为分子分析充分保留肿瘤细胞。根据临床、病理和分子生物学家的观点，我们在这里综述了分子生物标志物的诊断和预测价值，以符合现代多学科治疗肺癌的方法。
