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s of A Presentation by the winners of The Japanese Society of Pathology; Pathology Research Award in 2017 (in program order) Histopathological examination in animal models of atherosclerosis to metabolic syndrome Sohsuke Yamada Department of Pathology and Laboratory Medicine, Kanazawa Medical University Since atherosclerosis and its complications account for approximately up to 30% of cause of human death in the whole world, it is very critical to overcome this issue from the economical as well as medical aspects. I first focused on the histopathological viewpoints that the initiation to progression of atherosclerosis basically depends on inflammatory response. In order to elucidate its mechanism, we have thoroughly performed the in vivo and in vitro experiments together with the extensively morphological to biochemical and molecular analyses from the wide view, by using various genetically modified animal models of mice or rabbits, and various cell cultures. Furthermore, I recently aim to multidimensionally and comprehensively re-evaluate these chronic inflammatory diseases, via overlooking the entity of metabolic syndrome, manifesting as not only atherosclerosis but diabetes mellitus (DM) or non-alcoholic steatohepatitis (NASH). In the atherosclerotic lesions, besides vascular wallcomprising cells including smooth muscle cells (SMCs), we can histologically see various types of inflammatory cells, such as macrophages (MФ), whose complicated reactions consider to canonically regulate the promotion of atherosclerosis. We have figured out the mechanism(s) of metabolic syndrome including atherosclerosis, via extensively investigating the production and regulation of histamine, a classic inflammatory low-molecular-weight amine, apoptotic activities, oxidative stress and the regulation of lipid/bile acid metabolism, especially in those inflammatory lesions, at least in part. Based on a growing body of evidences using variable target genes-knockout mice, e.g., histidine decarboxylase (HDC), histamine receptors (HRs) or apoptosis signal-regulating kinase 1 (ASK1), the expression of receptor or apoptosis on MФ and SMC play a key role in the promotion or suppression of atherosclerosis to liver injury. But our serial in vivo studies can also provide new findings, that those crucial and complicated functions of histamine/HRs signaling or apoptotic activities uniquely depend on each animal model or each inflammatory phase. Moreover, since I focused on the results that oxidative stressors are one of critical factors for apoptotic stimulators, we have generated unique human peroxiredoxin 4 (hPRDX4) transgenic mice. We have revealed that the critical and diverse protective roles of PRDX4 against metabolic syndrome, i.e., DM, atherosclerosis, insulin resistance and/or NASH. We ultimately aim to contribute understanding the pathophysiology of life style-related diseases, through careful and precise investigation of those unique animal models. Post-genome comprehensive medical care for patients and at risk families with Birt-Hogg-Dub e syndrome Mitsuko Furuya Department of Molecular Pathology, Yokohama City University School of Medicine Birt-Hogg-Dub e (BHD) syndrome is an inherited disorder caused by a germline mutation of FLCN. The affected individuals have pulmonary cysts, fibrofolliculomas, and renal cell carcinomas (RCCs). In Japan, BHD syndrome had been studied as a familial pneumothorax; however, little was known about RCCs. We collected the cases and summarized genetic, pathological and epidemiologic information of 165 Japanese BHD families composed of 420 individuals. There were the three mutational hot spots in exon 11, 12 and 13. Approximately 70% of individuals presented with episodes of pneumothorax. Within FLCN mutation carriers over 40 years of age, 35% of them had RCCs. The most frequent histological types were chromophobe RCC (chRCC) and hybrid oncocytic/chromophobe tumor (HOCT). Papillary RCC and clear cell RCC occurred less frequently, suggesting promiscuous association between FLCN mutations and RCC phenotypes. Immunohistochemical analysis revealed that BHD-associated chRCCs and HOCTs were positively stained for distal tubule markers, which was similar to sporadic chRCCs. Around 40% of RCCs had FLCN second hits, but others did not. Copy number variation analysis revealed that BHD-associated RCCs, regardless of histological types, had balanced chromosomal state. All RCCs had copious numbers of loss of heterozygosity (LOH) in a wide range of chromosomes, © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd Pathology International 2017; xx: 1–5 doi:10.1111/pin.12595