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

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          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.

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          Most cited references29

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          Head and neck cancer.

          Most head and neck cancers are squamous cell carcinomas that develop in the upper aerodigestive epithelium after exposure to carcinogens such as tobacco and alcohol. Human papillomavirus has also been strongly implicated as a causative agent in a subset of these cancers. The complex anatomy and vital physiological role of the tumour-involved structures dictate that the goals of treatment are not only to improve survival outcomes but also to preserve organ function. Major improvements have been accomplished in surgical techniques and radiotherapy delivery. Moreover, systemic therapy including chemotherapy and molecularly targeted agents--namely, the epidermal growth factor receptor inhibitors--has been successfully integrated into potentially curative treatment of locally advanced squamous-cell carcinoma of the head and neck. In deciding which treatment strategy would be suitable for an individual patient, important considerations include expected functional outcomes, ability to tolerate treatment, and comorbid illnesses. The collaboration of many specialties is the key for optimum assessment and decision making. We review the epidemiology, molecular pathogenesis, diagnosis and staging, and the latest multimodal management of squamous cell carcinoma of the head and neck.
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            p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities.

            We describe the cloning of p63, a gene at chromosome 3q27-29 that bears strong homology to the tumor suppressor p53 and to the related gene, p73. p63 was detected in a variety of human and mouse tissues, including proliferating basal cells of epithelial layers in the epidermis, cervix, urothelium, and prostate. Unlike p53, the p63 gene encodes multiple isotypes with remarkably divergent abilities to transactivate p53 reporter genes and induce apoptosis. Importantly, the predominant p63 isotypes in many epithelial tissues lack an acidic N terminus corresponding to the transactivation domain of p53. We demonstrate that these truncated p63 variants can act as dominant-negative agents toward transactivation by p53 and p63, and we suggest the possibility of physiological interactions among members of the p53 family.
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              • Record: found
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              • Article: not found

              Clinical implications of the p53 tumor-suppressor gene.

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                Author and article information

                Journal
                J Oral Maxillofac Pathol
                J Oral Maxillofac Pathol
                JOMFP
                Journal of Oral and Maxillofacial Pathology : JOMFP
                Medknow Publications & Media Pvt Ltd (India )
                0973-029X
                1998-393X
                Sep-Dec 2016
                : 20
                : 3
                : 427-435
                Affiliations
                [1]Department of Pathology, International Medical University, Kuala Lumpur, Malaysia
                [1 ]Department of Medical Sciences, University of Queensland, Brisbane, Australia
                [2 ]Department of Oral and Maxillofacial Pathology and Radiology, The Ohio State University, Columbus, Ohio, United States of America
                [3 ]Department of Pathology, Hospital Tuanku Ja’afar, Seremban, Negeri Sembilan, Malaysia
                Author notes
                Address for correspondence: Dr. Sunil Pazhayanur Venkateswaran, International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia. E-mail: sunil_venkateswaran@ 123456imu.edu.my
                Article
                JOMFP-20-427
                10.4103/0973-029X.190945
                5051291
                27721608
                73bd7f62-c61b-48da-a279-2bfc5603aece
                Copyright: © Journal of Oral and Maxillofacial Pathology

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 20 June 2016
                : 04 August 2016
                Categories
                Original Article

                Pathology
                argyrophilic nuclear organizer regions,p73 protein,head and neck squamous cell carcinoma

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