Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Surgery material from 28 cases was studied. Thyroid adenoma differs from thyroid carcinoma by a lower level of expression of Ki-67 and bcl-2, while the mutated p53 expression is lacking. These indices may be used for early and differential diagnosis of thyroid carcinoma. Medullary carcinoma is a tumor with the highest malignant potential and p53 and bcl-2 may serve as markers of a higher degree of malignancy. Ki-67 may serve a marker of proliferative activity of tumors belonging to the same histological type. Thus, its high expression in follicular carcinoma is an index of a high proliferative activity of its cells, correlates with its rapid growth and should be taken into consideration in therapy and prognosis. Expression of bcl-2 clearly correlates with neuroendocrine differentiation of carcinoma and its highest expression was found in the medullary carcinoma as well as in the chromogranin positive cells of the papillary thyroid carcinoma. APUD amyloid deposits in medullary carcinoma and high levels of c-myc in adenomas indicate some genetic restructurizations in malignant and benign thyroid tumors.
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PMID:[Immunohistochemistry of biomolecular markers of early thyroid cancer]. 948 13

Combined phenotypes of cells with membrane and intracellular expression of apoptosis and proliferation regulation markers (p53, bcl-2, CD95, CD95L, Ki-67) were studied by flow cytometry of cell suspension from thyroid tissue specimens from patients with autoimmune diseases, adenoma, and thyroid cancer. The incidence of cell groups with phenotypes p53/Ki-67, p53/CD95, bcl-2/Ki-67, bcl-2/CD95, CD95/Ki-67, p53/CD95L, CD95/CD95L, and bcl-2/CD95L was evaluated and the density of receptor distribution on/in each cell group are presented. Patients with autoimmune diseases had high incidence of cells with phenotypes p53/Ki-67, p53/CD95, bcl-2/Ki-67, bcl-2/CD95, CD95/Ki-67, p53/CD95L, CD95/CD95L, and bcl-2/CD95L; cells with the bcl-2/CD95 phenotype were the most incident. Patients with thyroid adenoma had high levels of cells with p53/CD95L phenotype, while patients with thyroid cancer had significantly lower levels of p53 expression in the p53/CD95L cell group. The density of CD95L receptors on CD95/CD95L-positive cells was 4-7-fold higher in patients with thyroid tumors; the density of CD95L receptors on CD95/CD95L cells was maximum in thyroid adenoma and minimum in thyroid cancer. These data indicate differences in the expression of apoptosis and proliferation markers in thyroid adenoma, cancer, and autoimmune diseases. Analysis of the expression of these markers in the above diseases can be useful for differential diagnosis.
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PMID:Comparative analysis of cells with combined apoptosis and proliferation markers in thyroid tissue specimens from patients with cancer, adenoma, and autoimmune diseases. 2226 42

Gender bias in the incidence of thyroid cancer is well known, however, the underlying mechanism is largely unknown. The current study determines variations in the molecular characteristics of thyroid cancers between men and women. Normal and cancerous thyroid tissues were collected from a total of 125 men and women who underwent surgical thyroidectomy. Testosterone levels in serum and thyroid cancer tissues were elevated in women while it decreased in men compared to respective control groups; whereas, ligand binding activity increased in men and decreased in women. Androgen receptor (AR) mRNA expression increased in a majority of men while it decreased in a majority of women except those with follicular thyroid carcinoma (FTC). In thyroid cancers of women, Pearson's correlation analysis showed a positive correlation of AR mRNA with AR protein, CBP and Sp1, whereas AR mRNA showed a negative correlation with p53. In case of men, AR mRNA showed a positive correlation with AR and cyclin D1 proteins in papillary thyroid carcinoma (PTC); and CBP and Sp1 in follicular thyroid adenoma (FTA), whereas AR mRNA showed a positive correlation with p53. Our study identified for the first time that AR is posttranscriptionally regulated by miR-124a in thyroid cancer tissues. Further, our in vitro studies with a PTC cell line (NPA-87-1) showed miR-124a as the potent inhibitor of AR that impairs cell proliferation even in the presence of testosterone. Thus, the current study suggests that: (i) the varying pattern of testosterone level and AR status in thyroid tissues of men and women may predispose to the gender specific incidence of thyroid tumors and (ii) miR-124a plays a significant role in determining the AR gene expression pattern and thus, androgen mediated thyroid tumor growth.
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PMID:Androgen receptor expression in human thyroid cancer tissues: a potential mechanism underlying the gender bias in the incidence of thyroid cancers. 2238 53

The goal of the present study was to investigate whether p53 antibodies (Abs) could be a relevant marker for papillary thyroid carcinoma (PTC). Three types of enzyme-linked immunosorbent assay (ELISA) methods were developed for the detection of p53 Abs, including p53-ELISA, phage-SS-ELISA, and phage-SP-ELISA. A total of 304 patients, including 117 cases with thyroid adenoma and 187 PTC patients, were enrolled in this study. Expression of p53 protein and mutation in BRAF gene were evaluated in paraffin-embedded tissue from 44 patients with PTC, in order to elucidate their correlations with the presence of p53 Abs. Compared with p53-ELISA and phage-SS-ELISA, phage-SP-ELISA presented the highest detection efficiency of p53 Abs in patients with PTC, and a combination of these three ELISA systems could make the detection of p53 Abs more sensitive than using each of the individual ELISA methods. Furthermore, p53 Abs was positively associated with clinical stage (P = 0.044), node metastasis (P = 0.010), and p53 protein accumulation (P = 0.019). These results indicate that serum p53 Abs could be a useful marker for PTC.
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PMID:Detection of serum p53 antibodies from Chinese patients with papillary thyroid carcinoma using phage-SP-ELISA: correlation with clinical parameters. 2468 40

The goal of the present study was to evaluate the clinical and diagnostic value of both serum p53-antibodies (Abs) and preoperative fine needle aspiration cytology (FNAC) for BRAF mutation in patients with papillary thyroid carcinoma (PTC). A total of 312 patients, including thyroid adenoma (85) and PTC (227) were enrolled in this study. Two types of enzyme-linked immunosorbent assays (ELISA), phage-ELISA and p53-ELISA, were used to measure serum p53-Ab levels. Sanger sequencing was used to determine BRAF gene mutation in FNA samples. Phage-ELISA was more efficient than conventional p53-ELISA in measuring serum p53-Abs in PTC patients. BRAF mutation analysis with FNAC significantly improved PTC diagnostic sensitivity from 80.18% to 93.83% (P=0.001) and accuracy from 82.31% to 92.37% (P=0.005). Bothp53-Abs and BRAF mutation were positively associated with lymphatic metastasis and advanced TNM stages. Particularly, serum p53-Abs positively associated with multifocality (P=0.02), while BRAF mutation associated with extrathyoidal extension (P=0.01). Furthermore, PTC patients with both elevated serum p53-Abs and BRAF mutation had a higher prevalence of extrathyoidal extension (P=0.003), lymphnode metastasis (P=0.00), multifocality (P=0.04), and advanced TNM stages (P=0.004). Our results indicate that serum p53-Abs alone might not be a reliable biomarker for PTC diagnosis, but the combined analysis of serum p53-Abs and BRAF mutation in FNAC may be useful for optimizing surgical treatment and prognostic prediction of unfavorable clinicopathologic outcomes.
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PMID:Clinical significance of preoperative detection of serum p53 antibodies and BRAF(V600E) mutation in patients with papillary thyroid carcinoma. 2688 73

We aimed to identify differences in mutational status between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC). The study included 35 patients with FTA and 35 with FTC. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) samples from thyroidectomy. Next-generation sequencing (NGS) was performed with the 50-gene Ion AmpliSeq Cancer Hotspot Panel v2. Potentially pathogenic mutations were found in 14 (40%) FTA and 24 (69%) FTC patients (OR (95%CI) = 3.27 (1.22-8.75)). The number of mutations was higher in patients with FTC than FTA (p-value = 0.03). SMAD4 and STK11 mutations were present only in patients with FTA, while defects in FBXW7, JAK3, KIT, NRAS, PIK3CA, SMARCB1, and TP53 were detected exclusively in FTC patients. TP53 mutations increased the risk of FTC; OR (95%CI) = 29.24 (1.64-522.00); p-value = 0.001. FLT3-positivity was higher in FTC than in the FTA group (51.4% vs. 28.6%; p-value = 0.051). The presence of FLT3 and TP53 with no RET mutations increased FTC detectability by 17.1%, whereas the absence of FLT3 and TP53 with a presence of RET mutations increased FTA detectability by 5.7%. TP53 and FLT3 are candidate markers for detecting malignancy in follicular lesions. The best model to predict FTA and FTC may consist of FLT3, TP53, and RET mutations considered together.
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PMID:Differences in Mutational Profile between Follicular Thyroid Carcinoma and Follicular Thyroid Adenoma Identified Using Next Generation Sequencing. 3124 21

Molecular mechanisms underlying the pathogenesis and progression of malignant thyroid cancers, such as follicular thyroid carcinomas (FTCs), and how these differ from benign thyroid lesions, are poorly understood. In this study, we employed network-based integrative analyses of FTC and benign follicular thyroid adenoma (FTA) lesion transcriptomes to identify key genes and pathways that differ between them. We first analysed a microarray gene expression dataset (Gene Expression Omnibus GSE82208, n = 52) obtained from FTC and FTA tissues to identify differentially expressed genes (DEGs). Pathway analyses of these DEGs were then performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) resources to identify potentially important pathways, and protein-protein interactions (PPIs) were examined to identify pathway hub genes. Our data analysis identified 598 DEGs, 133 genes with higher and 465 genes with lower expression in FTCs. We identified four significant pathways (one carbon pool by folate, p53 signalling, progesterone-mediated oocyte maturation signalling, and cell cycle pathways) connected to DEGs with high FTC expression; eight pathways were connected to DEGs with lower relative FTC expression. Ten GO groups were significantly connected with FTC-high expression DEGs and 80 with low-FTC expression DEGs. PPI analysis then identified 12 potential hub genes based on degree and betweenness centrality; namely, TOP2A, JUN, EGFR, CDK1, FOS, CDKN3, EZH2, TYMS, PBK, CDH1, UBE2C, and CCNB2. Moreover, transcription factors (TFs) were identified that may underlie gene expression differences observed between FTC and FTA, including FOXC1, GATA2, YY1, FOXL1, E2F1, NFIC, SRF, TFAP2A, HINFP, and CREB1. We also identified microRNA (miRNAs) that may also affect transcript levels of DEGs; these included hsa-mir-335-5p, -26b-5p, -124-3p, -16-5p, -192-5p, -1-3p, -17-5p, -92a-3p, -215-5p, and -20a-5p. Thus, our study identified DEGs, molecular pathways, TFs, and miRNAs that reflect molecular mechanisms that differ between FTC and benign FTA. Given the general similarities of these lesions and common tissue origin, some of these differences may reflect malignant progression potential, and include useful candidate biomarkers for FTC and identifying factors important for FTC pathogenesis.
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PMID:Network-Based Genetic Profiling Reveals Cellular Pathway Differences Between Follicular Thyroid Carcinoma and Follicular Thyroid Adenoma. 3209 41