title: Standard immunohistochemistry efficiently screens for anaplastic lymphoma kinase rearrangements in differentiated thyroid cancer.
abstract: The anaplastic lymphoma kinase (ALK) gene is frequently rearranged in various types of cancer and is highly responsive to targeted therapeutics. We developed a system to detect rearrangement of ALK in a large group of Korean thyroid cancer patients. We screened 474 malignant or benign thyroid tumor cases to identify ALK fusions. Expression and translocation of the ALK gene were analyzed by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and digital multiplexed gene expression (DMGE) analysis in formalin-fixed paraffin-embedded tissues. Four cases of rearrangement of ALK were detected by IHC, and these cases were validated with FISH on 189 samples. On the other hand, DMGE analysis using Nanostring detected three out of four IHC-positive cases. Two rearrangements of ALK were striatin (STRN)-ALK fusions, which were identified by 5' RACE analysis. Rearrangements of ALK were found exclusively in v-raf murine sarcoma viral oncogene homolog B (BRAF) WT papillary carcinomas. Given the wide availability and accuracy of IHC for detecting ectopic expression of ALK in the thyroid, we suggest that IHC-based screening can be a practical method for identifying patients with ALK rearrangements in differentiated thyroid cancer.
authors.affiliation: Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Gahee
authors.initials: G
authors.lastname: Park
authors.affiliation: Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Tae Hyuk
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Hae-Ock
authors.initials: HO
authors.lastname: Lee
authors.affiliation: Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Jung Ah
authors.initials: JA
authors.lastname: Lim
authors.affiliation: Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Won
authors.affiliation: Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.affiliation: Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Kyu Eun
authors.initials: KE
authors.lastname: Lee
authors.affiliation: Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Do Joon
authors.initials: DJ
authors.lastname: Park
authors.affiliation: Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea Samsung Genome InstituteSamsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments ofInternal MedicinePathology SurgeryBiomedical SciencesSeoul National University College of Medicine, Seoul, KoreaDepartment of Internal MedicineEulji University School of Medicine, Eulji General Hospital, Seoul, KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea woongyang.park@samsung.com.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D055088:Early Detection of Cancer; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; gene rearrangement; immunohistochemistry; thyroid cancer