BRAFV600E Mutation, RET/PTC1 and PAX8-PPAR Gamma Rearrangements in Follicular Epithelium Derived Thyroid Lesions - Institutional Experience and Literature Review

Abstract

Background: Thyroid cancers are the most frequently occurring endocrine malignancy worldwide. In Turkey, thyroid cancers are ranked 2 nd on the incidence list in women, with a rate of 16.2%, but they are not included among the top 10 cancer types in men. Aims: To identify the contribution of the BRAF V600E mutation, and the RET/PTC1 and PAX8-PPARγ rearrangements in the diagnosis and differential diagnosis of follicular epithelial-derived thyroid lesions. Study Design: Retrospective clinical and molecular genetic study. Methods: A total of 86 thyroid cases diagnosed between 2001 and 2012 at the Department of Pathology were included in the retrospective study group. Samples best representing the lesion and comprising capsules were chosen in the selection of paraffin blocks pertaining to the cases. The BRAF V600E mutation, and the RET/PTC1 and PAX8-PPARγ rearrangements were investigated in all cases. Results: The BRAF V600E mutation was observed in 12 out of 37 papillary carcinoma cases (32.4%), in 1 out of 15 follicular carcinoma cases (6.6%), and in 1 out of 7 undifferentiated carcinoma cases (14.3%). No mutation was detected in benign lesions. The RET/PTC1 rearrangement was detected in 2 out of 7 undifferentiated carcinoma cases (28.6%), and in 1 out of 15 follicular carcinoma cases (6.6%). No gene rearrangement was detected in benign lesions. The PAX8-PPARγ rearrangement was detected in 5 out of 15 follicular thyroid carcinoma cases (33.3%) and in 1 out of 15 follicular adenoma cases (6.6%). Conclusion:The BRAF V600E mutation and RET/PTC1 rearrangement were effective in distinguishing the follicular epithelium-derived benign and malignant lesions of the thyroid in the resection materials. The BRAF V600E mutation was rather specific to papillary carcinoma in the thyroid, and in cases where the BRAF V600E mutation was detected, multi-centricity, lymph node metastasis and capsular invasion findings were observed more frequently compared to cases in which no mutation was observed. The PAX8-PPARγ rearrangement was observed to be more effective in the differentiation of adenomas and carcinomas in follicular neoplasms of the thyroid, whereas the RET/PTC1 analysis contributed to the differential diagnosis of papillary carcinoma histogenesis at a frequency of 29% in undifferentiated thyroid carcinomas.

Targeted next‑generation sequencing of cancer‑related genes in thyroid carcinoma: A single institution's experience

“…BRAF mutations in TC have been vigorously investigated since the early 2000s (17,18). The frequency of the BRAF V600E mutation reportedly ranges from 32 to 80% in patients with PC (4,(19)(20)(21). Several large-scale multicenter studies reported that the average frequency of the BRAF V600E mutation in PC is approximately 48% (22,23).…”

Mutation Profile of Well-Differentiated Thyroid Cancer in Asians

“…The PAX8/PPARγ fusion gene is most commonly found in FTC, the follicular variant PTC, and benign follicular adenomas, though the prevalence of these rearrangements varies significantly among studies. The mean frequency in FTC is 5.6% in Asia, 43.8% in the Americas, and 27.4% in Europe ( Table 4 ) [ 36 38 45 46 73 74 75 76 77 78 79 80 81 82 83 84 ]. The low frequency of PAX8/PPARγ rearrangements in Asia is particularly noteworthy, with one Japanese study failing to identify a single PAX8/PPARγ rearrangement in FTC [ 73 ].…”

BRAF mutation, TERT promoter mutation, and HER2 amplification in sporadic or neurofibromatosis‐related neurofibromas and malignant peripheral nerve sheath tumors: do these molecules have a signature in malignant transformation?

“…The loss of NF-1 protein function leads to increased RAS signaling. The BRAF kinase molecule is also a downstream RAS effector, and its mutations are found in numerous cancers such as melanomas and thyroid carcinomas (11,20). New advances in molecular pathology have provided information that specific mutations are associated with particular tumors, but BRAF mutation can be expected in malignant melanomas but also can be found in common melanocytic nevi.…”