Detection of novel and potentially actionable anaplastic lymphoma kinase (ALK) rearrangement in colorectal adenocarcinoma by immunohistochemistry screening

• Published in: Oncotarget Vol. 6; no. 27; pp. 24320 - 24332
• Main Authors: Lee, Jeeyun, Kim, Hee Cheol, Hong, Jung Yong, Wang, Kai, Kim, Sun Young, Jang, Jiryeon, Kim, Seung Tae, Park, Joon Oh, Lim, Ho Yeong, Kang, Won Ki, Park, Young Suk, Lee, Jiyun, Lee, Woo Yong, Park, Yoon Ah, Huh, Jung Wook, Yun, Seong Hyeon, Do, In-Gu, Kim, Seok Hyung, Balasubramanian, Sohail, Stephens, Philip J, Ross, Jeffrey S, Li, Gang Gary, Hornby, Zachary, Ali, Siraj M, Miller, Vincent A, Kim, Kyoung-Mee, Ou, Sai-Hong Ignatius
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 15.09.2015
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - chemistry; Benzamides - chemistry; Cell Line, Tumor; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Female; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - metabolism; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Rearrangement; Genomics; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Indazoles - chemistry; Male; Middle Aged; Mutation; Phosphorylation; Pyrazoles - chemistry; Pyridines - chemistry; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Reproducibility of Results; Republic of Korea; Research Paper; Sensitivity and Specificity; Tissue Array Analysis; Young Adult; anaplastic lymphoma kinase (ALK) rearrangement; colorectal carcinoma; immunohistochemistry; next generation sequencing
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.4462

Anaplastic lymphoma kinase (ALK) rearrangement has been detected in colorectal carcinoma (CRC) using advanced molecular diagnostics tests including exon scanning, fluorescence in situ hybridization (FISH), and next generation sequencing (NGS). We investigated if immunohistochemistry (IHC) can be used to detect ALK rearrangement in gastrointestinal malignancies. Tissue microarrays (TMAs) from consecutive gastric carcinoma (GC) and CRC patients who underwent surgical resection at Samsung Medical Center, Seoul, Korea were screened by IHC using ALK monoclonal antibody 5A4. IHC positive cases were confirmed by FISH, nCounter assays, and NGS-based comprehensive genomic profiling (CGP). ALK IHC was further applied to CRC patients enrolled in a pathway-directed therapeutic trial. Four hundred thirty-two GC and 172 CRC cases were screened by IHC. No GC sample was ALK IHC positive. One CRC (0.6%) was ALK IHC positive (3+) that was confirmed by ALK FISH and a novel CAD-ALK (C35; A20) fusion variant that resulted from a paracentric inversion event inv(2)(p22-21p23) was identified by CGP. One out of 50 CRC patients enrolled in a pathway-directed therapeutic trial was ALK IHC positive (3+) confirmed by ALK FISH and found to harbor the EML4-ALK (E21, A20) fusion variant by CGP. Growth of a tumor cell line derived from this EML4-ALK CRC patient was inhibited by ALK inhibitors crizotinib and entrectinib. ALK IHC is a viable screening strategy for identifying ALK rearrangement in CRC. ALK rearrangement is a potential actionable driver mutation in CRC based on survival inhibition of patient tumor-derived cell line by potent ALK inhibitors.