MOLECULAR DETECTION OF MECT1-MAML2 FUSION GENE IN MUCOEPIDERMOID CARCINOMA WITH ORDINARY AND VARIANT HISTOLOGY: A STUDY USING ARCHIVAL PARAFFIN EMBEDDED TISSUE

Mucoepidermoid carcinoma (MEC) has been characterized by t (11; 19)(q21; p13). This chromosomal translocation has been recently shown to generate a MECT1- MAML2 fusion gene. MEC can pose diagnostic challenges when they are of high-grade, of variant histologic appearance and occurring in an unusual site. The aim of this study was to evaluate the frequency of the MECT1-MAML2 fusion gene among primary salivary gland MECs and extrasalivary gland MECs, together with some histological variants and its role as a possible diagnostic adjunct, comparing the salivary gland tumors including Warthin's tumor(WT)，pleomorphic adenoma(PA)，and adenoid cystic carcinoma(ACC). Using a reverse transcription-polymerase chain (RT-PCR)-based approach, we assayed for the MECT1-MAML2 transcript in 39 cases for which paraffin- embedded tumor tissue with adequate RNA was available. These included 19 MECs，10 WTs， five PAs， and five ACCs. The MECT1-MAML2 fusion gene transcript was detected in 16 (84.2%) of 19 MECs. These positive cases included two cases of MEC with WT-like areas，a sclerosing MEC and a clear cell MEC. Three negative cases were high- grade MECs. Two of them were not easy to distinguish from squamous cell carcinoma. The MECT1-MAML2 fusion gene was negative in all cases of WT，PA and ACC. The potential usefulness of MECT1-MAML2 fusion gene expression as a molecular marker in the diagnosis of MEC is supported

カナダにおける国家統合 : 1920年代の地域主義とマッケンジー・キング自由党政権

学位の種別:課程博士University of Tokyo(東京大学

総督の権限とカナダ連邦政治 : 1926 年キング―ビング事件と進歩党を中心に

Since its formation, Canada has been a country of multiple ethnicities and regions that respectively have their own interests. The 2016 Canadian census reports that more than 250 ethnic origins and ancestries exist in the country. In addition, the Canadian federal government has historically faced the political challenge of the regional movements of the Atlantic and Western provinces and Quebecʼs separatist movement.According to Arendt Lijphart, a scholar of comparative politics, a consensus form of democracy, which is conducive to creating compromise among different groups regardless of their size, is advantageous especially for countries facing social divide. Switzerland and Belgium with their federal system and proportional representation system are typical examples of consensus form of democracy.While Canada also adopted federalism, it followed the British parliamentary and electoral systems, that is to say, it is a majoritarian form of democracy. Given Canadaʼs deep ethnic and regional cleavages, the following research questions arise. Does consensus form of democracy better fit Canada for stabilizing society? Has there been a movement toward institutional reform in Canadian political history?If we look to the past, we can acknowledge negative perspectives casted on the existing political system. This occurred with the emergence of the Progressives, a third party established from a regional protest movement in the Western provinces in 1920. The politicians of this new party insisted on a sort of consensus form of democracy that included the necessity of cooperative politics among different political groups, a proportional representation system, and a coalition government. This study argues that despite the Progressive Partyʼs political influence in parliament through its power of the casting vote, the King-Byng affair of 1926, a political dispute between the governor general and the prime minister, negatively affected the Progressives. In conclusion, this study insists that the first challenge against the existing political system ended when the Progressives receded in the middle of the 1920s

多党制下のカナダにおけるデュヴェルジェ的政党政治の希求

Canada has been classified as a counter-example to the political theory "Duverger\u27s law," which posits that a single-member plurality electoral system (SMP) tends to produce a two-party system. In fact, a multi-party system appeared after the federal election of 1921. A regional protest party challenged the existing Liberal Party and Conservative Party, resulting in winning the second largest seats in the House of Commons. Particularly, the 1993 federal election marked a turning point in the history of Canadian politics. Canada saw an emergence of two regionally based parties, and the status of the largest opposition was consecutively occupied by third parties.Since that election, scholars of Canadian party politics have focused on and explained the aspect of change in the party system, party organization, party representation, and electoral campaign strategies. Interestingly, however, if we look at the traditional Liberal Party and Progressive Conservative Party (today\u27s Conservative Party, we can acknowledge that they have continuously emphasized on being "nationa" in their representation; that is, the party should secure support from every region of the country, even after the politicization of a regional cleavage in the 1993 federal election. Being "national" has been their political tenet since the Canadian Confederation of 1867, for it is believed as a means of "national unity" in the country with highly distinctive regions.With a focus on the aspect of continuity in the traditional two parties, the sole governing parties so far, this article aims to delineate the nature of Canadian party politics, which is unfolded under the undeniable multi-party system. As mentioned above, Canada is a deviation from Duverger\u27s law; paradoxically however, we can empirically observe that the traditional two parties have pursued a return to a two party system regardless of its feasibility. That is demonstrated by the fact that there is an absence of coalition government, but there are many minority governments in Canada as the traditional two parties have persisted in being "national" on their own and not accepted third parties as a coalition partner after the election. In sum, Canadian party politics can be regarded as a pursuit of one that Duverger\u27s law generally assumes

Analysis of Patients Visiting Niigata University Medical and Dental Hospital with Chief Complaints of Metal Allergy and/or Focal Infection in the Previous 8 Years

Dental metal allergyand dental focal infection are possible causes of dermatological diseases, but have been the subjects of few reports to date. We have been treating such patients in our special clinicfor more than 20 years.The purpose of the present study was to investigate the mouths of patients visitingour dental hospital over an 8-year period, with the aim of clarifyingwhether dental metal allergy andjor dental focal infection affects their dermatologic conditions.We surveyed all clinicalrecords of the 185 patients who visited Niigata UniversityMedicaland Dental Hospitalwith chiefcomplaints of dental metal allergysince 2002. Diagnosticsof skin diseases, periodontal records, periapical lesions, dental caries, dental metal series patch test results and Electron Probed Micro-Analysis(EPMA)data were investigated. Ninety-two(49%) patients were sufferingfrom pustulosis palmaris et plantaris and 20 (11%)patients had lichen planus. Eighty-two(49%)patients showed positive reactions on patch testing. Based on the result of patch tests, Nishowed the highest positivity rate (62%,51 patients), but on EPMA,the number of patients with Ni as an allergen was 14 (27%).On the other hand, more than 98%of patients who showed positive reactions on patch test to Pd and Au had these metals in their dental prostheses. In addition, 112 (60%)patients showed the possibilityof dental focal infections

Analysis of Patients Visiting Niigata University Medical and Dental Hospital with Chief Complaints of Metal Allergy and/or Focal Infection in the Previous 8 Years

Dental metal allergy and dental focal infection are possible causes of dermatological diseases, but have been the subjects of few reports to date. We have been treating such patients in our special clinic for more than 20 years.The purpose of the present study was to investigate the mouths of patients visiting our dental hospital over an 8-year period, with the aim of clarifying whether dental metal allergy and/or dental focal infection affects their dermatologic conditions.We surveyed all clinical records of the 185 patients who visited Niigata University Medical and Dental Hospital with chief complaints of dental metal allergy since 2002. Diagnostics of skin diseases, periodontal records, periapical lesions, dental caries, dental metal series patch test results and Electron Probed Micro-Analysis (EPMA) data were investigated. Ninety-two (49%) patients were suffering from pustulosis palmaris et plantaris and 20 (11%) patients had lichen planus. Eighty-two (49%) patients showed positive reactions on patch testing. Based on the result of patch tests, Ni showed the highest positivity rate (62%, 51 patients), but on EPMA, the number of patients with Ni as an allergen was 14 (27%). On the other hand, more than 98% of patients who showed positive reactions on patch test to Pd and Au had these metals in their dental prostheses. In addition, 112 (60%) patients showed the possibility of dental focal infection

浸潤および血管新生を通しての人肝細胞癌の進行におけるケラチン19分子の役割

BACKGROUND: Keratin (K) 19-positive hepatocellular carcinoma (HCC) is well known to have a higher malignant potential than K19-negative HCC: However, the molecular mechanisms involved in K19-mediated progression of HCC remain unclear. We attempted to clarify whether K19 directly affects cell survival and invasiveness in association with cellular senescence or epithelial-mesenchymal transition (EMT) in K19-positive HCC. METHODS: K19 expression was analysed in 136 HCC surgical specimens. The relationship of K19 with clinicopathological factors and survival was analysed. Further, the effect of K19 on cell proliferation, invasion, and angiogenesis was examined by silencing K19 in the human HCC cell lines, HepG2, HuH-7, and PLC/PRF/5. Finally, we investigated HCC invasion, proliferation, and angiogenesis using K19-positive HCC specimens. RESULTS: Analysis of HCC surgical specimens revealed that K19-positive HCC exhibited higher invasiveness, metastatic potential, and poorer prognosis. In vitro experiments using the human HCC cell lines revealed that K19 silencing suppressed cell growth by inducting apoptosis or upregulating p16 and p27, resulting in cellular senescence. In addition, transfection with K19 siRNA upregulated E-cadherin gene expression, significantly inhibited the invasive capacity of the cells, downregulated angiogenesis-related molecules such as vasohibin-1 (VASH1) and fibroblast growth factor 1 (FGFR1), and upregulated vasohibin-2 (VASH2). K19-positive HCC specimens exhibited a high MIB-1 labelling index, decreased E-cadherin expression, and high microvessel density around cancer foci. CONCLUSION: K19 directly promotes cancer cell survival, invasion, and angiogenesis, resulting in HCC progression and poor clinical outcome. K19 may therefore be a novel drug target for the treatment of K19-positive HCC.博士（医学）・乙第1399号・平成29年3月15日© The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Analysis of Patients Visiting Niigata University Medical and Dental Hospital with Chief Complaints of Metal Allergy And/or Focal Infection in the Previous 8 Years

Dental metal allergy and dental focal infection are possible causes of dermatological diseases, but have been the subjects of few reports to date. We have been treating such patients in our special clinic for more than 20 years.The purpose of the present study was to investigate the mouths of patients visiting our dental hospital over an 8-year period, with the aim of clarifying whether dental metal allergy and/or dental focal infection affects their dermatologic conditions.We surveyed all clinical records of the 185 patients who visited Niigata University Medical and Dental Hospital with chief complaints of dental metal allergy since 2002. Diagnostics of skin diseases, periodontal records, periapical lesions, dental caries, dental metal series patch test results and Electron Probed Micro-Analysis (EPMA) data were investigated. Ninety-two (49%) patients were suffering from pustulosis palmaris et plantaris and 20 (11%) patients had lichen planus. Eighty-two (49%) patients showed positive reactions on patch testing. Based on the result of patch tests, Ni showed the highest positivity rate (62%, 51 patients), but on EPMA, the number of patients with Ni as an allergen was 14 (27%). On the other hand, more than 98% of patients who showed positive reactions on patch test to Pd and Au had these metals in their dental prostheses. In addition, 112 (60%) patients showed the possibility of dental focal infection

腹膜および胸膜悪性中皮腫におけるEGFR発現の比較

An evaluation of epidermal growth factor receptor (EGFR) phenotypic expression in malignant pleural and peritoneal mesothelioma was undertaken, using immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) analysis. Thirty-eight malignant mesothelioma (MM) specimens were subjected to IHC staining and FISH to evaluate the expression of EGFR protein and gene status. Overall positive IHC reaction was detected in 20/38 (53%) cases, in 11/22 (50%) pleural MM, and in 9/16 (56%) peritoneal MM. Our study confirmed that EGFR membranous expression is a common feature in MM, but not in benign mesothelial lesion. Thirty-seven cases did not show a gene copy number gain. Only one case showed a copy number gain. The protein overexpression of EGFR was not related to a gene copy number gain.博士（医学）・乙第1299号・平成24年5月28日© 2012 The Authors. Pathology International© 2012 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd

乳腺腺様嚢胞癌においてサイトケラチン5/6の腺腔形成細胞の染色性は類似病変との鑑別に有用である

Adenoid cystic carcinoma (AdCC) of the breast is an uncommon but distinct neoplasm composed of a dual cell population polarized around true glandular (luminal) spaces and pseudolumina. The aim of this study was to clarify whether various immunohistochemical markers (CK7, EMA, CD117, p63, calponin, CD10, S100, CK5/6, CK14, vimentin, and type IV collagen) can distinguish between the two cell types in classical AdCC (n = 14) and in collagenous spherulosis (n = 5). The sensitivity and specificity of these 11 markers to distinguish luminal from abluminal cells were evaluated using a curve created by plotting the true-positive rate (sensitivity) against the false-positive rate (1 - specificity) at threshold settings of 0, 10, 50, and 70 %. The most sensitive and specific markers for luminal cells in AdCC were CK7 and EMA; those for abluminal cells were type IV collagen, p63, and vimentin. CD10 and S100 did not act as abluminal markers in AdCC. CK5/6, one of the basal/myoepithelial markers, was expressed more frequently in luminal than in abluminal cells of AdCC. Thus, CK5/6 immunostaining resulted in a reverse expression pattern, analogous to what we recently documented in clear cells in mammary adenomyoepithelioma. In conclusion, compared with myoepithelial/abluminal cells of normal breast or collagenous spherulosis, the neoplastic abluminal cells of classical AdCC are characterized by enhanced vimentin and attenuated CD10 and S100. Furthermore, the luminal cells of AdCC show a unique aberrant staining pattern for CK5/6 that may aid in the differential diagnosis.博士（医学）・乙第1389号・平成28年11月24日© Springer-Verlag Berlin Heidelberg 2016The final publication is available at Springer via http://dx.doi.org/10.1007/s00428-016-1963-