Recently, RET/PTC rearrangements have been shown not only in PTC but also in benign thyroid lesions. In recent years, thyroid cancer has been at the forefront of molecular pathology as a result of the consequences of the Chernobyl disaster and the recognition of the role of RET/PTC rearrangements in papillary thyroid carcinomas (PTCs). The evolution of molecular tests for thyroid nodules followed the discovery of various diagnostic and prognostic molecular markers of thyroid cancer that can be applied to thyroid FNA .
The most frequent initial manifestation of thyroid cancer is the appearance of a nodüle, most of which are benign nodules. Estimating, less than 5% are malignant nodules. In reality, some cases are misdiagnosed, and many patients undergo unnecessary surgery. Because of this, an accurate pre-surgery evaluation is required. In most cases, the most reliable diagnostic test for thyroid nodules is fine needle aspiration (FNA) cytology.
In our study, we performed the molecular analysis using a procedure that involves RET/PTC gene mutation in easily obtainable FNA samples. We aimed to attempt to improve the efficacy of the FNA diagnosis of thyroid nodules and thus patient management.
In our previous study, RET/PTC in tumor tissue was determined positive in 67(66,3%) of totally 101 patients and RET/PTC determined negative in 34(33,7%) . In our recent newer study, A total of 75% FNA RET rearrangements were detected in the 20 PTC. RET/PTC positive was detected in 35% of cases without cancer (sensitivity 75%, specificity 65%). RET/PTC rearrangements was found to be statistically significant in PTC (p = 0,003). In first years, RET/PTC was considered a PTC specific. Later times, it was also found sporadically in benign thyroid lesions [18,19]. Sapio MR and all. investigated whether a search for the oncogenes RET/PTC, TRK and BRAF(V600E) in thyroid aspirates could refine an uncertain diagnosis. On final analysis, no false-positive results were reported in 131 samples and five out of seven carcinomas (71%) were correctly diagnosed . In our study, the FNA RET/PTC results were (80%) PTC, (75%) suspect citology, (40%) atypyc nodule, (20%) benign nodule, (30%) nondiagnostic nodule.
In a multicenter study in Italy, the rate of mutation-positive FNAs were found related to the risk of malignancy of in each Bethesda diagnostic categories class . On the other hand, in a study in Germany, their data suggest that the application of the current seven-gene panel in a routine primary referral setting does not improve the presurgical diagnosis of thyroid FNAs .
For the first time in literature, our study investigated RET/PTC in according to ATA USG risk groups (A- high suspicion, B- intermediate suspicion and C- low suspicion). Significant correlation was found between A-USG group (80%), B-USG group (45%) and C-USG group (20%) in of RET/PTC rearrangements (p = 0.001) (Table 2). Similarly with the literature, in our study significant correlation was found between USG groups and PTC (respectively group A,B,C: 60%, 30%, 10%)(p = 0.003)(Table 3) . When we considered patients with PTC according to histological types, they were composed of classical type and follicular variant (FV). The FV is the most common type of PTC after classic PTC . In our study, classical type and FV of PTC prevalence was similar with literature . In our study, in frequency between Classic type and Follicular varient PTC significant correlation was found with USG groups (p = 0.019) (Table 4).
The prevalence of RET rearrangements have been examined in cohorts of papillary carcinomas in many countries. The prevalence has shown a marked geographic discordance [17,25–28]. RET/PTC1 and RET/PTC3 are the most encountered types . Similarly, RET/PTC1 and RET/PTC3 the most type of RET/PTC was found in our study.
The relationship between RET/PTC prevalence and types of PTC were investigated. No correlation difference was found between RET/PTC and types of PTC (Table 5).
In a study Basolo F at al. investigated the prognostic meaning of RET/PTC rearrangement on the long term outcome of PTC. No correlation was found between RET expression and other parameters such as age at diagnosis, sex, histological variant and tumor class .
The relationship between prognostic factors and RET/PTC prevalence and types in patients with PTC were investigated in our study. There was no statistical difference related to TSH, age and tumor diameter in both PTC type (Classic and Follicular) and RET PTC type (1,3) (Table 6 and Table 7). No correlation was found with RET/PTC releated to multifocality, bilaterality, soft tissue invasion and lymph node metastases.
In the beginning of the literature firstly, our study investigated the prevalence of RET/PTC mutation in thyroid nodules according to risk category ATA USG. On the other hand, we were determined the relation of the between RET/PTC and malignancy. No differant was found between USG groups and TSH, sex, age at diagnosis and tumor diameter (Table 8). In addition, No difference was found with sex in USG groups neither RET/PTC nor PTC. There was a statistical difference related tumor to diameter with groups A and C (Table 8).
The weaknesses of our study were the absence of other molecular markers and the number of patients. Strengths of the study were the cytological evaluation and histopathological confirmation of RET/PTC according to the ATA USG risk category for the first time.
As a result, Cytological analysis is now, practically routinely, being joined with molecular analysis to enable the patholog to make a more actual diagnosis. Molecular testing of FNA samples improves presurgical diagnosis. RET/PTC frequency in FNA significant difference was found in ATA USG risk category. RET/PTC was found to be significantly higher in the diagnoses of the PTC with 75% sensitivity and 65% specificity. However, a larger clinical study will be required to verify this resuls.