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      Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

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          Abstract

          Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important advances for detecting high-risk patients, monitoring preventive interventions, and assessing cancer risk and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from studies using appropriate animal carcinogenesis models. New approaches, such as molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy.

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          Most cited references130

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          Nomenclature and classification of potentially malignant disorders of the oral mucosa.

          At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the UK issues related to terminology, definitions and classification of oral precancer were discussed by an expert group. The consensus views of the Working Group are presented here. The term, 'potentially malignant disorders', was recommended to refer to precancer as it conveys that not all disorders described under this term may transform into cancer. Critically evaluating all definitions proposed so far for oral leukoplakia, the Working Group agreed that the term leukoplakia should be used to recognize 'white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer'. An outline was proposed for diagnosing oral leukoplakia that will prevent other oral white disorders being misclassified as leukoplakia. The Working Group discussed the caveats involved in the current use of terminology and classification of oral potentially malignant disorders, deficiencies of these complex systems, and how they have evolved over the past several decades. The terminology presented in this report reflects our best understanding of multi-step carcinogenesis in the oral mucosa, and aspires to engender consistency in use.
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            A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications.

            The concept of "field cancerization" was first introduced by Slaughter et al. [D. P, Slaughter et al., Cancer (Phila.), 6: 963-968, 1953] in 1953 when studying the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. It was proposed to explain the development of multiple primary tumors and locally recurrent cancer. Organ systems in which field cancerization has been described since then are: head and neck (oral cavity, oropharynx, and larynx), lung, vulva, esophagus, cervix, breast, skin, colon, and bladder. Recent molecular findings support the carcinogenesis model in which the development of a field with genetically altered cells plays a central role. In the initial phase, a stem cell acquires genetic alterations and forms a "patch," a clonal unit of altered daughter cells. These patches can be recognized on the basis of mutations in TP53, and have been reported for head and neck, lung, skin, and breast cancer. The conversion of a patch into an expanding field is the next logical and critical step in epithelial carcinogenesis. Additional genetic alterations are required for this step, and by virtue of its growth advantage, a proliferating field gradually displaces the normal mucosa. In the mucosa of the head and neck, as well as the esophagus, such fields have been detected with dimensions of >7 cm in diameter, whereas they are usually not detected by routine diagnostic techniques. Ultimately, clonal divergence leads to the development of one or more tumors within a contiguous field of preneoplastic cells. An important clinical implication is that fields often remain after surgery of the primary tumor and may lead to new cancers, designated presently by clinicians as "a second primary tumor" or "local recurrence," depending on the exact site and time interval. In conclusion, the development of an expanding preneoplastic field appears to be a critical step in epithelial carcinogenesis with important clinical consequences. Diagnosis and treatment of epithelial cancers should not only be focused on the tumor but also on the field from which it developed.
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              “Field cancerization” in oral stratified squamous epithelium. Clinical implications of multicentric origin

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                Author and article information

                Journal
                Patholog Res Int
                PRI
                Pathology Research International
                SAGE-Hindawi Access to Research
                2042-003X
                2011
                22 May 2011
                : 2011
                : 431246
                Affiliations
                1Director TCI-CaRP, 5-1-2 Minami-Uzura, Gifu City, Gifu 500-8285, Japan
                2Department of Oncologic Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Shikawa 920-0293, Japan
                3Department of Pharmacy, Kinjo Gakuin University of Pharmacy, Moriyama-Ku, Nagoya, Aichi 463-8521, Japan
                4Department of Physical Therapy, Kansai University of Health Sciences, Kumatori-Machi, Sennan-Gun, Osaka 590-0482, Japan
                Author notes

                Academic Editor: Stefan E. Pambuccian

                Article
                10.4061/2011/431246
                3108384
                21660266
                21b544aa-88c8-4eec-af51-751884ca8bf3
                Copyright © 2011 Takuji Tanaka et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 October 2010
                : 19 March 2011
                Categories
                Review Article

                Pathology
                Pathology

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