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 frequentlyoccurring endocrine malignancy worldwide. In Turkey,thyroid cancers are ranked 2nd on the incidence list inwomen, with a rate of 16.2%, but they are not includedamong the top 10 cancer types in men. Aims: To identify the contribution of the BRAFV600E mutation, and the RET/PTC1 and PAX8-PPARγ rear - rangements in the diagnosis and differential diagnosisof follicular epithelial-derived thyroid lesions. Study Design: Retrospective clinical and moleculargenetic study. Methods: A total of 86 thyroid cases diagnosed be- tween 2001 and 2012 at the Department of Pathologywere included in the retrospective study group. Sam- ples best representing the lesion and comprising cap- sules were chosen in the selection of paraffin blockspertaining to the cases. The BRAFV600E mutation, andthe RET/PTC1 and PAX8-PPARγ rearrangements wereinvestigated in all cases. Results: The BRAFV600E mutation was observed in 12out of 37 papillary carcinoma cases (32.4%), in 1 outof 15 follicular carcinoma cases (6.6%), and in 1 out of7 undifferentiated carcinoma cases (14.3%). No muta- tion was detected in benign lesions. The RET/PTC1 rearrangement was detected in 2 out of 7 undifferentiated carcinoma cases (28.6%), and in1 out of 15 follicular carcinoma cases (6.6%). No generearrangement was detected in benign lesions.The PAX8-PPARγ rearrangement was detected in 5 outof 15 follicular thyroid carcinoma cases (33.3%) and in1 out of 15 follicular adenoma cases (6.6%).Conclusion: The BRAFV600E mutation and RET/PTC1rearrangement were effective in distinguishing the fol-licular epithelium-derived benign and malignant lesionsof the thyroid in the resection materials. The BRAFV600Emutation was rather specific to papillary carcinoma inthe thyroid, and in cases where the BRAFV600E mutationwas detected, multi-centricity, lymph node metastasisand capsular invasion findings were observed morefrequently compared to cases in which no mutationwas observed. The PAX8-PPARγ rearrangement wasobserved to be more effective in the differentiation ofadenomas and carcinomas in follicular neoplasms ofthe thyroid, whereas the RET/PTC1 analysis contrib-uted to the differential diagnosis of papillary carcinomahistogenesis at a frequency of 29% in undifferentiatedthyroid carcinomas.