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Diffuse sclerosing variant of papillary thyroid carcinoma: major genetic alterations and prognostic implications
Author(s) -
Joung Ji Y,
Kim Tae H,
Jeong Dae J,
Park SunMi,
Cho Yoon Y,
Jang Hye W,
Jung Yoon Y,
Oh Young L,
Yim Hyun S,
Kim YooLi,
Chung Jae H,
Ki ChangSeok,
Kim Sun W
Publication year - 2016
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12902
Subject(s) - neuroblastoma ras viral oncogene homolog , thyroid carcinoma , hras , kras , gene rearrangement , sanger sequencing , thyroiditis , pax8 , medicine , cancer research , pathology , biology , mutation , gastroenterology , thyroid , cancer , genetics , gene , colorectal cancer , transcription factor
Aim Diffuse sclerosing variant of papillary thyroid carcinoma ( DSV ‐ PTC ) is an uncommon variant of PTC , and its prognostic significance remains controversial. The aim of this study was to investigate the major genetic alterations of DSV ‐ PTC and their prognostic implications. Methods and results We included 37 patients with DSV ‐ PTC who underwent thyroid surgery and had formalin‐fixed paraffin‐embedded samples. We tested for a panel of genetic alterations, including BRAF V 600E , NRAS codon 61, HRAS codon 12/13/61 and KRAS codon 12/13 point mutations as well as RET / PTC 1 , RET / PTC 3 and PAX 8/ PPAR γ rearrangements using reverse transcription real‐time polymerase chain reaction ( PCR ). All genetic alterations found on PCR were confirmed by Sanger sequencing. Associations between the identified genetic alterations and clinicopathological characteristics were evaluated. Among 37 cases of DSV ‐ PTC , 17 were positive for RET / PTC 1 (46%), six for RET / PTC 3 (16%) and nine for BRAF V 600E (24%). All mutations/rearrangements were mutually exclusive. The remaining five cases had none of the above genetic alterations. DSV ‐ PTC with RET / PTC 3 rearrangement was associated with advanced‐stage disease, including T4 and distant metastasis ( P < 0.05). Patients with RET / PTC 3 showed a higher frequency of persistent disease ( P < 0.01). In contrast, DSV ‐ PTC with RET / PTC 1 was associated with a higher prevalence of disease remission ( P < 0.05) and coexistent Hashimoto's thyroiditis ( P < 0.01). Conclusion Taken together, RET / PTC rearrangement was the major genetic alteration seen in patients with DSV ‐ PTC , and the RET / PTC 3 rearrangement was associated with advanced stage at diagnosis and poor clinical outcome.