Characteristics of PTEN Mutation in Thyroid Tumours: A Retrospective Chart Review

Abstract

While some studies suggest that PTEN mutations correlate with a low-risk phenotype in pediatric thyroid nodules, the relationship between the mutation and malignancy in the adult populations is abstruse. This study investigated whether PTEN mutations result in thyroid malignancy, and whether these malignancies are aggressive. This multicenter study involved 316 patients who underwent preoperative molecular testing, and subsequent lobectomy or total thyroidectomy at two quaternary care hospitals. A four-year retrospective review was performed on the 16 charts of patients that opted for surgery following a positive PTEN mutation on molecular testing results from January 2018 to December 2021. Of the total 16 patients, 37.5% (n = 6) had malignant tumours, 18.75% (n = 3) had non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), and 43.75% (n = 7) had benign disease. Aggressive features were detected in 33.33% of the malignant tumours. Malignant tumours were found to have a statistically significant higher allele frequency (AF). The aggressive nodules were all poorly differentiated thyroid carcinomas (PDTCs) with copy number alterations (CNAs) and the highest AFs.

Thyroid nodules with DICER1 mutation or PTEN alteration: A comparative cytologic, clinical, and molecular study of 117 FNA cases

“…In the two published FNA series of PTEN ‐associated thyroid lesions (Table 8), the most common Bethesda classification was Category III, followed by Category IV 39,43 . Our FNA cohort, in a trend similar to our DICER1 cohort, showed the same pattern, with 54.3% of PTEN cases classified as TBSRTC Category III and 29.6% as TBSRTC Category IV.…”

“…In addition, Laury et al 40 show that thyroid nodules with a DICER1 mutation are more frequently hyperplastic with variable pseudopapillary features compared with the more microfollicular pattern in PTEN-altered nodules, this finding is not as readily apparent based on our cytologic cohort and those of others (Table 8). 31,32,39,40,43 The limitation of the current study is the concentration of DICER1 and PTEN-altered cases belonging to the indeterminate TBSRTC categories. Furthermore, the case cohort does not reflect the full spectrum of benign DICER1 and PTEN-related thyroid nodules classified by FNA as benign (TBSRTC category II) because those cases would neither be triaged for molecular testing nor undergo surgical resection.…”

“…Although approximately two-thirds of our cohort was diagnosed as follicular adenomas and adenomatous nodules at resection, the other one-third of cases comprised NIFTP, follicular carcinoma, PTC, and one case of anaplastic thyroid carcinoma. Only two other series of PTEN-altered FNA cases report their cytologic features, but they show a similar broad spectrum of follicular-patterned histology at resection although the FNA cohort by Bandargal et al 39 contained an increased proportion of PTEN-mutated NIFTPs or malignant tumors, some having aggressive features (Table 8). 43 Quaytman et al 43 concluded that isolated somatic PTEN-mutated thyroid tumors are predominantly benign, and the ROM is likely to be higher when combined with other mutations.…”

“…Most PTEN alterations are non‐syndromic and are associated with limited clinical information, which also limits their identification in FNA cases of PTEN‐altered nodules. This is further exaggerated by the fact that PTEN protein loss is more frequent in tumorigenesis than PTEN genetic alterations 39 . Our FNA cohort of PTEN‐altered thyroid nodules was enriched in cases with PTEN mutations because these would be identified through the application of molecular testing such as Thyroseq to nodules classified in the indeterminate Bethesda categories.…”

Possible Markers for Distinguishing benign and Malignant Thyroid Tumors and Predicting Malignancy in Patients with Genetic Predisposition to Cancer

“…The balance between ROS and antioxidants is maintained by activating antioxidant systems or upregulating antioxidant gene expression [ 9 , 10 ]. There is increasing evidence to suggest that the tumor suppressor genes are involved in the regulation of the cell cycle and other important cellular process, such as DNA reparation, replication, transcription [ 11 , 12 ], and the regulation of oxidative stress through the upregulation of antioxidant response [ 13 , 14 ]. This upregulation leads to an increase in the expression of several genes, including glutathione S-transferases, which decrease the levels of ROS [ 15 , 16 ], and mutation of these genes contributes to the intensification of oxidative stress and further malignant transformation of the tumor cells.…”