ALK-rearranged lung cancer in Chinese: a comprehensive assessment of clinicopathology, IHC, FISH and RT-PCR.
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.
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Yuan
Y
Li
Yunjian
Y
Pan
Rui
R
Wang
Yihua
Y
Sun
Haichuan
H
Hu
Xuxia
X
Shen
Yongming
Y
Lu
Lei
L
Shen
Xiongzeng
X
Zhu
Haiquan
H
Chen
D000230:Adenocarcinoma / Q000175:diagnosis / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000912:Antibodies, Neoplasm / Q000276:immunology; D044466:Asian People / Q000235:genetics*; D002681:China; D004252:DNA Mutational Analysis; D005260:Female; D005629:Frozen Sections; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D000912:Antibodies, Neoplasm; C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases