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      Human Papillomavirus Infection and Its Possible Correlation with p63 Expression in Cervical Cancer in Japan, Mongolia, and Myanmar

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          Abstract

          Although human papillomavirus (HPV) 16 is the cause of cervical cancer in most countries including Japan, the involvement of cervical cancer with HPV types in Mongolian and Myanmar populations is largely unknown. We examined the expression of HPV in formalin-fixed and paraffin-embedded cervical tissues from 40 Japanese, 32 Mongolian, and 30 Myanmar cervical cancer patients. We performed immunohistochemistry using anti-HPV16 and anti-HPV 1, 6, 11, 16, 18 and 31 cocktail and then correlated it with the expression of Ki-67 and p63. HPV 16 was detected in 72%, 65% and 50% of Japanese, Mongolian and Myanmar cervical cancer patients, respectively, whereas 5 (13%) of the 40 patients, 8 (25%) of the 32 patients and 7 (23%) of the 30 patients in HPV 16-negative cancers were positive for other HPV types included in the cocktail, respectively. Ki-67 labeling index (LI) as well as p63 LI was significantly higher in HPV 16-positive patients than in HPV 16-negative ones in the Japanese and Mongolian samples. p63 expression was significantly associated with stage III and IV in Japan and Mongolia. These findings suggest that HPV 16 may be associated with cell proliferative activity and tumor progression, possibly depending upon the expression of p63 in the cervical cancer. In addition, immunohistochemical detection for distinguishing the type of HPV may also be useful for cervical cancer in the clinical setting.

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          Most cited references39

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          p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development.

          The p63 gene, a homologue of the tumour-suppressor p53, is highly expressed in the basal or progenitor layers of many epithelial tissues. Here we report that mice homozygous for a disrupted p63 gene have major defects in their limb, craniofacial and epithelial development. p63 is expressed in the ectodermal surfaces of the limb buds, branchial arches and epidermal appendages, which are all sites of reciprocal signalling that direct morphogenetic patterning of the underlying mesoderm. The limb truncations are due to a failure to maintain the apical ectodermal ridge, a stratified epithelium, essential for limb development. The embryonic epidermis of p63-/- mice undergoes an unusual process of non-regenerative differentiation, culminating in a striking absence of all squamous epithelia and their derivatives, including mammary, lacrymal and salivary glands. Taken together, our results indicate that p63 is critical for maintaining the progenitor-cell populations that are necessary to sustain epithelial development and morphogenesis.
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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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              Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group.

              Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries. There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation. Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types. More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries. Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics. We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types. A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity. HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries. HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5%. HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common. There was significant geographic variation in the prevalence of some less common virus types. A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America. In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors). Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide. They also suggest that most genital HPVs are associated with cancer, at least occasionally. The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs.
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                Author and article information

                Journal
                Acta Histochem Cytochem
                AHC
                Acta Histochemica et Cytochemica
                Japan Society of Histochemistry and Cytochemistry (Tokyo, Japan )
                0044-5991
                1347-5800
                29 December 2009
                22 December 2009
                : 42
                : 6
                : 181-190
                Affiliations
                [1 ]Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
                [2 ]Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
                [3 ]Department of Health, National Health Laboratory, Ministry of Health; Department of Public Health Laboratory, University of Public Health; Department of Medical Science, Ministry of Health, Yangon, Union of Myanmar
                [4 ]Pathology Research Division, Department of Medical Research (Lower Myanmar), Yangon, Union of Myanmar
                [5 ]Yangon Central Women’s Hospital, Yangon, Union of Myanmar
                [6 ]Oncology Department, Center of Pathology, Ministry of Health, Mongolia
                Author notes
                Correspondence to: Professor Takehiko Koji, Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1–12–4 Sakamoto, Nagasaki 852–8523, Japan. E-mail: tkoji@ 123456nagasaki-u.ac.jp
                Article
                AHC09030
                10.1267/ahc.09030
                2808501
                20126571
                d4f5bf9c-49a3-4ff4-8362-c0c6be6ee006
                © 2009 The Japan Society of Histochemistry and Cytochemistry

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

                History
                : 13 September 2009
                : 10 October 2009
                Categories
                Regular Article

                Clinical chemistry
                hpv,japan,myanmar,cervical cancer,mongolia
                Clinical chemistry
                hpv, japan, myanmar, cervical cancer, mongolia

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