A Detailed Clinicopathologic Study of ALK-translocated Papillary Thyroid Carcinoma. (May 2015)

• Record Type: Journal Article
• Authors: Chou, Angela; Fraser, Sheila; Toon, Christopher W.; Clarkson, Adele; Sioson, Loretta; Farzin, Mahtab; Cussigh, Carmen; Aniss, Ahmad; O'Neill, Christine; Watson, Nicole; Clifton-Bligh, Roderick J.; Learoyd, Diana L.; Robinson, Bruce G.; Selinger, Christina I.; Delbridge, Leigh W.; Sidhu, Stanley B.; O'Toole, Sandra A.; Sywak, Mark; Gill, Anthony J.
• Is Part Of: American journal of surgical pathology. Volume 39:Number 5(2015)
• Publication Date: 2015-05
• Subjects: Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000000368
• Languages: English
• ISSNs: 0147-5185

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>Pathogenic <italic>ALK</italic> 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 <italic>ALK</italic>-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 <italic>ALK</italic> translocations were identified in 36 PTCs with distant metastases, 28 poorly differentiated (insular) carcinomas, and 20 anaplastic carcinomas. All 14 patients with <italic>ALK</italic> translocations were female (<italic>P</italic>=0.0425), and translocations occurred at a younger age (mean 38 vs. 48 y, <italic>P</italic>=0.0289 in unselected patients). <italic>ALK</italic> translocation was an early clonal event present in all neoplastic cells and mutually exclusive with <italic>BRAF</italic><sup><italic>V600E</italic></sup> mutation. <italic>ALK</italic> 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 <italic>ALK</italic>-translocated and can be identified by screening IHC followed by FISH. <italic>ALK</italic> translocations may be more common in young females and diffuse sclerosing variant PTC but do not connote more aggressive disease.</p> </sec> </abstract>