p53 expression in cytology samples may represent a marker of early‐stage cancer

Abstract

Background TP53 gene plays a major role in the negative control of cell proliferation and in the regulation of signaling cascades. TP53 mutation may have a relevant role in the malignant transformation of thyroid cells as well as thyroid tumor progression. TP53 mutation has been detected only in few well differentiated thyroid carcinomas and is absent in benign conditions. Methods A total of 162 prospective thyroid cytology and corresponding histological samples diagnosed from atypia of indeterminate significance (AUS) to malignant, were studied via immunocytochemistry for p53. Hence, 50 benign lesions (B) were used as negative control. Molecular analysis for p53 only was performed. Results The cytology resulted in 50 B, 48 AUS, 40 follicular neoplasms (FNs), 23 suspicious for malignancy (SFM), and 1 malignant (M) case. The authors reported 102 negative and 60 positive p53 cases. The 60 positive cases included 27 cases with weak and/or focal cytoplasmic positivity (+1) and 33 with cases moderate (2+) to strong (3+) cytoplasmic and/or nuclear expression. Overall, 71 cases had histology (2 B, 11 AUS, 37 FN, 20 SFM, and 1 M) including 61.7% benign and 38.2% malignant diagnoses. Only 16 of 71 (5 FN, 10 SFM, and 1 M) were p53‐positive. Furthermore, 100% AUS and 86.5% FN cases were p53‐negative, none of which had malignant histology. All p53‐positive cases were associated with a larger nodule size, tall‐cell variant subtype, multifocality, extra thyroidal infiltration, and nodal metastases. Noninvasive follicular thyroid neoplasm with papillary like nuclear features were negative for p53. Few discrepancies in p53 intensity were observed on histology; there were no differences with the molecular testing. Conclusions p53 might be useful in discriminating thyroid follicular lesions. p53 is likely to be a useful diagnostic marker in recognizing indeterminate lesions that are well‐differentiated thyroid cancers.

Indeterminate Thyroid Nodules: From Cytology to Molecular Testing

“…The reason is that the presence of mutations in these two genes is associated with aggressive histological phenotypes, which are usually not classified in the categories with indeterminate cytology. Therefore, the frequency of TERT promoter and TP53 mutations in indeterminate nodules is very low [ 47 , 48 ].…”

Pitfalls in Thyroid Fine-Needle Aspiration Cytopathology: An Approach to Atypical Findings

“…Loss of CD56 expression and overexpression of cyclin D1 on ICC are reported to show high predictability for malignant thyroid tumors on subsequent histopathology; however, the literature is limited on this topic [71][72][73]. Recently, P53 was shown to serve as a valuable diagnostic marker in cytology specimens to identify indeterminate lesions that represent well-differentiated thyroid cancers on subsequent histologic preparations [74].…”