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Argyrophilic nuclear organizer region and p73 expression in head and neck squamous cell carcinomas: Teammates or adversaries?

ABSTRACT: CONTEXT:Head and neck squamous cell carcinoma (HNSCC) consists of squamous cell carcinomas (SCCs) arising in the upper aerodigestive tract and accounts for 5% of cancers worldwide. In Malaysia, cancers of the nasopharynx, larynx, tongue and oral cavity are among the top twenty most common cancers in men. Argyrophilic nuclear organizer regions (AgNORs) are increased from normal mucosa to premalignant lesions to malignant lesions and have been associated with tumor grade and prognosis of patients. Although p73 is not mutated in human cancers, high levels of p73 expression have been associated with tumor differentiation status and patient prognosis. AIMS:To investigate the correlation between AgNORs and p73 immunoexpression. SETTINGS AND DESIGN:Fifty-two formalin-fixed, paraffin-embedded HNSCC cases and ten controls were collected from the Hospital. SUBJECTS AND METHODS:Tissue blocks were sectioned, dewaxed and rehydrated before silver nitrate staining to determine the AgNOR count and immunohistochemical staining to determine the p73 expression. Adopting the scoring system used by Chen et al. for p73 staining, the proportion of positively stained cells in the whole epithelial layer was determined. Staining was considered positive if >10% of epithelial cells were stained. STATISTICAL ANALYSIS USED:Spearman's correlation coefficient was calculated using SPSS 18 software to determine the relationship between the p73 score against tumor differentiation, mean AgNOR counts and tumor grade and between the mean AgNOR count and p73 score. RESULTS:Positive results were found in the immunoexpression of p73. Positive results were seen with the staining of AgNOR; however, in comparison with the entire sample size, a significant correlation between mean AgNOR count and p73 immunohistochemical expression was not obtained. CONCLUSIONS:AgNOR count showed a linear and decreasing trend as the p73 score increases. This correlation was statistically insignificant.

SUBMITTER: Venkateswaran SP

PROVIDER: S-EPMC5051291 | biostudies-literature | 2016 Sep-Dec

REPOSITORIES: biostudies-literature

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Argyrophilic nuclear organizer region and p73 expression in head and neck squamous cell carcinomas: Teammates or adversaries?

Venkateswaran Sunil Pazhayanur SP Nathan Leviana Ercylina LE Mutalik Vimi Sunil VS Shamsuddin Noor Hasni NH

Journal of oral and maxillofacial pathology : JOMFP 20160901 3

<h4>Context</h4>Head and neck squamous cell carcinoma (HNSCC) consists of squamous cell carcinomas (SCCs) arising in the upper aerodigestive tract and accounts for 5% of cancers worldwide. In Malaysia, cancers of the nasopharynx, larynx, tongue and oral cavity are among the top twenty most common cancers in men. Argyrophilic nuclear organizer regions (AgNORs) are increased from normal mucosa to premalignant lesions to malignant lesions and have been associated with tumor grade and prognosis of p ...[more]

PMID: 27721608

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Project description:BACKGROUND:Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high mortality. The identification of specific HNSCC biomarkers will increase treatment efficacy and limit the toxicity of current therapeutic strategies. Long non-coding RNAs (lncRNAs) are promising biomarkers. Accordingly, here we investigate the biological role of ZFAS1 and its potential as a biomarker in HNSCC. METHODS:The expression level of ZFAS1 in HNSCC cell lines was analyzed using qRT-PCR. Based on the HNSCC TCGA data, the ZFAS1 expression profile, clinicopathological features, and expression of correlated genes were analyzed in patient tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. The interaction between lncRNA:miRNA and miRNA:mRNA was tested using available online tools. All statistical analyses were accomplished using GraphPad Prism 5. RESULTS:The expression of ZFAS1 was up-regulated in the metastatic FaDu cell line relative to the less aggressive SCC-25 and SCC-040 and dysplastic DOK cell lines. The TCGA data indicated an up-regulation of ZFAS1 in HNSCCs compared to normal tissue samples. The ZFAS1 levels typically differed depending on the cancer stage and T-stage. Patients with a lower expression of ZFAS1 presented a slightly longer disease-free survival and overall survival. The analysis of genes associated with ZFAS1, as well its targets, indicate that they are linked with crucial cellular processes. In the group of patients with low expression of ZFAS1, we detected the up-regulation of suppressors and down-regulation of genes associated with epithelial-to-mesenchymal transition (EMT) process, metastases, and cancer-initiating cells. Moreover, the negative correlation between ZFAS1 and its host gene, ZNFX1, was observed. The analysis of interactions indicated that ZFAS1 has a binding sequence for miR-150-5p. The expression of ZFAS1 and miR-150-5p is negatively correlated in HNSCC patients. miR-150-5p can regulate the 3'UTR of EIF4E mRNA. In the group of patients with high expression of ZFAS1 and low expression of miR-150-5p, we detected an up-regulation of EIF4E. CONCLUSIONS:In HNSCC, ZFAS1 displays oncogenic properties, regulates important processes associated with EMT, cancer-initiating cells, and metastases, and might affect patients' clinical outcomes. ZFAS1 likely regulates the cell phenotype through miR-150-5p and its downstream targets. Following further validation, ZFAS1 might prove a new and valuable biomarker.

Dataset Information

Argyrophilic nuclear organizer region and p73 expression in head and neck squamous cell carcinomas: Teammates or adversaries?

Publications

Argyrophilic nuclear organizer region and p73 expression in head and neck squamous cell carcinomas: Teammates or adversaries?

Similar Datasets

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