PMID- 25501013
OWN - NLM
STAT- MEDLINE
DCOM- 20150615
LR  - 20190221
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 39
IP  - 5
DP  - 2015 May
TI  - A detailed clinicopathologic study of ALK-translocated papillary thyroid 
      carcinoma.
PG  - 652-9
LID - 10.1097/PAS.0000000000000368 [doi]
AB  - Pathogenic ALK translocations have been reported in papillary thyroid carcinoma 
      (PTC). We developed and validated a screening algorithm based on 
      immunohistochemistry (IHC), followed by fluorescence in situ hybridization (FISH) 
      in IHC-positive cases to identify ALK-rearranged PTC. IHC and FISH were performed 
      in a cohort of 259 thyroid carcinomas enriched for aggressive variants. IHC was 
      positive in 8 cases, 6 confirmed translocated by FISH (specificity 75%). All 251 
      IHC-negative cases were FISH negative (sensitivity 100%). Having validated this 
      approach, we performed screening IHC, followed by FISH in IHC-positive cases in 
      an expanded cohort. ALK translocations were identified in 11 of 498 (2.2%) of all 
      consecutive unselected PTCs and 3 of 23 (13%) patients with diffuse sclerosing 
      variant PTCs. No ALK translocations were identified in 36 PTCs with distant 
      metastases, 28 poorly differentiated (insular) carcinomas, and 20 anaplastic 
      carcinomas. All 14 patients with ALK translocations were female (P=0.0425), and 
      translocations occurred at a younger age (mean 38 vs. 48 y, P=0.0289 in 
      unselected patients). ALK translocation was an early clonal event present in all 
      neoplastic cells and mutually exclusive with BRAF mutation. ALK translocation was 
      not associated with aggressive clinicopathologic features (size, stage, 
      metastasis, vascular invasion, extrathyroidal extension, multifocality, risk for 
      recurrence, radioiodine resistance). We conclude that 2.2% of PTCs are 
      ALK-translocated and can be identified by screening IHC followed by FISH. ALK 
      translocations may be more common in young females and diffuse sclerosing variant 
      PTC but do not connote more aggressive disease.
FAU - Chou, Angela
AU  - Chou A
AD  - *Cancer Diagnosis and Pathology Research Group  section sign section signSydney Vital Translational 
      Research Centre, Kolling Institute of Medical Research  section signUniversity of Sydney 
      Endocrine Surgical Unit **Hormones and Cancer Group, Cancer Genetics Laboratory, 
      Kolling Institute of Medical Research Departments of  paragraph signAnatomical Pathology 
      #Endocrinology, Royal North Shore Hospital, St Leonards daggerDepartment of Anatomical 
      Pathology SYDPATH, St Vincent's Hospital double daggerKinghorn Cancer Centre and Cancer 
      Research Program, Garvan Institute of Medical Research, Darlinghurst  parallelHistopath 
      Pathology, North Ryde daggerdaggerDepartment of Tissue Pathology and Diagnostic Oncology, 
      Royal Prince Alfred Hospital, Camperdown double daggerdouble daggerUniversity of Sydney, Sydney, NSW, 
      Australia.
FAU - Fraser, Sheila
AU  - Fraser S
FAU - Toon, Christopher W
AU  - Toon CW
FAU - Clarkson, Adele
AU  - Clarkson A
FAU - Sioson, Loretta
AU  - Sioson L
FAU - Farzin, Mahtab
AU  - Farzin M
FAU - Cussigh, Carmen
AU  - Cussigh C
FAU - Aniss, Ahmad
AU  - Aniss A
FAU - O'Neill, Christine
AU  - O'Neill C
FAU - Watson, Nicole
AU  - Watson N
FAU - Clifton-Bligh, Roderick J
AU  - Clifton-Bligh RJ
FAU - Learoyd, Diana L
AU  - Learoyd DL
FAU - Robinson, Bruce G
AU  - Robinson BG
FAU - Selinger, Christina I
AU  - Selinger CI
FAU - Delbridge, Leigh W
AU  - Delbridge LW
FAU - Sidhu, Stanley B
AU  - Sidhu SB
FAU - O'Toole, Sandra A
AU  - O'Toole SA
FAU - Sywak, Mark
AU  - Sywak M
FAU - Gill, Anthony J
AU  - Gill AJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Algorithms
MH  - Anaplastic Lymphoma Kinase
MH  - Carcinoma/genetics/*pathology
MH  - Carcinoma, Papillary
MH  - Child
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Sensitivity and Specificity
MH  - Thyroid Cancer, Papillary
MH  - Thyroid Neoplasms/genetics/*pathology
MH  - Tissue Array Analysis
MH  - Translocation, Genetic
MH  - Young Adult
PMC - PMC4415964
COIS- Conflicts of Interest and Source of Funding: Supported by the Cancer Institute 
      NSW through the Sydney Vital Translational Research Centre. S.O.T. and A.J.G. 
      report receiving honoraria from lectures from Pfizer, manufacturers of 
      crizotinib. S.O.T. was also supported by the Sydney Breast Cancer Foundation for 
      this study. For the remaining authors none were declared.
EDAT- 2014/12/17 06:00
MHDA- 2015/06/16 06:00
PMCR- 2015/04/30
CRDT- 2014/12/16 06:00
PHST- 2014/12/16 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/06/16 06:00 [medline]
PHST- 2015/04/30 00:00 [pmc-release]
AID - 10.1097/PAS.0000000000000368 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2015 May;39(5):652-9. doi: 10.1097/PAS.0000000000000368.