Clinical significance of RET/PTC and p53 protein expression in sporadic papillary thyroid carcinoma

Division of Endocrinology, Hospital General i Universitari Vall d'Hebron, Barcelona, Spain.
Histopathology (Impact Factor: 3.45). 02/2007; 50(2):225-31. DOI: 10.1111/j.1365-2559.2006.02555.x
Source: PubMed


Rearranged during Transfection (RET)/papillary thyroid carcinoma (PTC) and p53 are two genes involved in the pathogenesis of PTC. It has been suggested that RET/PTC expression is associated with higher rates of local extension and lymph node involvement, whereas p53 mutations are more frequent in poorly differentiated and anaplastic carcinomas. In addition, experimental studies have shown that p53 activity can modify the behaviour of PTC carrying RET/PTC. The aim of this study was to investigate the expression of both RET/PTC and p53 in order to evaluate their usefulness as prognostic factors.
Resected specimens of 61 cases of PTC were studied immunohistochemically using a polyclonal antibody to RET and a monoclonal antibody to p53 protein. RET/PTC expression was associated with extrathyroid extension of PTC, at diagnosis (P < 0.05). In contrast, no relationship between p53 immunoreactivity and clinical status was found. In addition, p53 expression was more prevalent among RET/PTC+ patients, and significantly influenced the relationship observed between RET/PTC and extrathyroid extension of the disease.
Our results suggest that immunohistochemistry for both PTC/RET and p53 could be useful in the clinical evaluation of patients with PTC.

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Available from: Jordi Mesa, Feb 13, 2015
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    • "e mean number of lymph node metastases was present ( Morita et al . , 2008 ) . Horie et al . ( 2001 ) also said that overexpression of p53 protein significantly correlated with large tumor size and the presence of capsular invasion ( Horie et al . , 2001 ) . But several studies ( Park et al . , 1998 ; Kalidag et al . , 2007 ; Jung et al . , 2007 ; Zafon et al . , 2007 ; Cvejic et al . , 2008 ; Hamzany et al . , 2012 ) found no association between p53 positivity and clinicopathologic data . In this study all parameters ( age , tumor size , multiplicity , extrathyroidal extension , vascular invasion , lymph node metastasis and mean number of metastatic lymph node ) revealed no significant correlation w"
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    ABSTRACT: Background: P53 protein expression has been detected immunohistochemically in papillary thyroid carcinoma(PTC). We investigated the relations between its expression and clinicopathologic features and its significance as a diagnostic marker. Materials and methods: We compared and evaluated 93 patients in whom thyroidectomy with lymph node dissection had been performed to treat PTC for clinicopathologic significance and 102 patients with 23 papillary thyroid overt carcinomas (POC), 57 papillary thyroid microcarcinomas(PMC), 5 follicular adenomas (FA), 5 Hashimoto's thyroiditis (HT) and 12 nodular hyperplasias (NH) for significance as a diagnostic marker. Expression of p53 protein was evaluated immunohistochemically in sections of paraffin- embedded tissue. Results: Statistical analysis showed significantly different expression of p53 in PTC versus other benign thyroid lesions (BTL).The diagnostic sensitivity and specificity were 85.0% and 72.7%, respectively. Overexpression of p53 protein was observed in 44 of the 93 PTC cases (47.3%), but no significant correlation between p53 protein overexpression and clinicopathologic features (age, size, multiplicity, lymph node metastasis, extrathyroidal extension and vascular invasion) was noted. Conclusions: p53 is valuable to distinguish PTC from other BTL, but there is no correlation between p53 protein overexpression and clinicopathologic features.
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    • "Somatic TP53 gene mutations have been reported in about half of all cancers and are believed to be critical determinants of the phenotype of many forms, including thyroid tumors [22]. TP53 has long been known to be rarely mutated in well-differentiated thyroid tumors, whereas it is frequently altered in poorly differentiated or undifferentiated cancers [19, 23, 24]. However, the paradigm that this tumor suppressor gene is only involved in advanced cancer progression is contradicted by a series of evidence indicating that it also plays an important role in the early stages of gastric [25], hepatocellular [26], lung [27], and many other tumors, including thyroid cancer [23]. "
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    ABSTRACT: Background: Besides its major role in cell proliferation, DNA repair, and apoptosis, functional p53 protein is involved in the induction of antitumor cytotoxic-T-cell activity against carcinoma cells. We aimed to investigate p53 and immune cell markers utility as diagnostic and prognostic markers of differentiated thyroid cancer (DTC). Methods: ACIS-III system was used to evaluate p53 and immune cell markers including tumor-associated macrophages (TAM); CD68 and tumor-infiltrating lymphocytes (TIL) subsets such as CD3, CD4, CD8, and CD20 in 206 thyroid carcinomas, 105 benign nodules, and 18 normal tissues. Also, TP53 was sequenced in 78 out of 164 patients with papillary thyroid carcinoma. Results: P53 expression was observed more frequently in malignant than in benign lesions (P < 0.0001) and helped discriminate follicular patterned lesions. In addition, p53 was more frequent in smaller (P = 0.0015), unique tumors (P = 0.0286), with thyroiditis (P = 0.0486) and without metastasis at diagnosis (P = 0.0201). TAM was more frequent in P53 negative tumors (P = 0.002). Infiltration of CD8+ TIL was found in 61.7% of P53 positive and 25.6% of P53 negative DTC (P < 0.001). Conclusions: We suggest that p53 and CD8+ TIL immune profile analysis might be useful in DTC.
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    • "Chromosomal rearrangement of the gene encoding the transmembrane tyrosine kinase receptors ret and trk is one identified early step in the development of these tumors. RET/PTC genetic alterations have been found in 40% and 60% of papillary carcinomas in adults and children, respectively, and are the most common mutation found in the Chernobyl radiation-induced thyroid carcinomas [74–76]. "
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