ALK-rearranged lung cancer in Chinese: a comprehensive assessment of clinicopathology, IHC, FISH and RT-PCR

• Published in: PloS one Vol. 8; no. 7; p. e69016
• Main Authors: Li, Yuan, Pan, Yunjian, Wang, Rui, Sun, Yihua, Hu, Haichuan, Shen, Xuxia, Lu, Yongming, Shen, Lei, Zhu, Xiongzeng, Chen, Haiquan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.07.2013; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - enzymology; Adenocarcinoma - immunology; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; ALK protein; Analysis; Anaplastic Lymphoma Kinase; Antibodies; Antibodies, Neoplasm - immunology; Asian Continental Ancestry Group - genetics; Biology; Cancer; China; Clinical medicine; DNA Mutational Analysis; Female; Fluorescence; Frozen Sections; Gene fusion; Gene Rearrangement - genetics; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lung cancer; Lung cancer, Non-small cell; Lung diseases; Lung Neoplasms - diagnosis; Lung Neoplasms - enzymology; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lymphoma; Male; Medicine; Middle Aged; Mucus; Mutation; Non-Hodgkin's lymphomas; Oncogene Proteins, Fusion - genetics; Oncology; Pathology; Polymerase chain reaction; Protein-tyrosine kinase; Receptor Protein-Tyrosine Kinases - genetics; Reverse Transcriptase Polymerase Chain Reaction; Reverse transcription; Signaling; Studies; Surgery; Thoracic surgery; Translocation; Tumors; Viral antibodies; Young Adult; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0069016

Approximately 3-7% of non-small cell lung cancers harbor an anaplastic lymphoma kinase (ALK) gene fusion, constituting a new molecular subtype of lung cancer that responds to crizotinib, an ALK inhibitor. Although previous studies have evaluated ALK-rearranged lung cancers, the comprehensive analysis of lung cancer in Chinese has not well assessed. Herein, we identified 44 cases of ALK-rearranged samples by fluorescent in-situ hybridization (FISH), immunohistochemistry (IHC), and reverse transcription polymerase chain reaction (RT-PCR) in a large number of surgically resected lung cancers. All 44 ALK-rearranged lung cancers were adenocarcinomas, with 2 cases having additional focal squamous components. The goal was to analyse the clinicopathological features of ALK-rearranged lung adenocarcinomas. Our data showed that a cribriform structure, prominent extracellular mucus and any type of mucous cell pattern may be either sensitive or specific to predict an ALK rearrangement. We used FISH as the standard detection method. We compared the ALK rearrangement accuracy of FISH, RT-PCR and IHC. RT-PCR could define both the ALK fusion partner and the fusion variant, but seemed unable to detect all translocations involving the ALK gene. It is noteworthy that IHC using the D5F3 antibody (Cell Signaling Technology) showed higher sensitivity and specificity than the ALK1 antibody (Dako). Therefore, we conclude that IHC remains a cost-effective and efficient technique for diagnosing ALK rearrangements and that D5F3 can be the optimal screening antibody in clinical practice.