32 results on '"Fukayama"'
Search Results
2. Extraskeletal osteosarcoma: MDM2 and H3K27me3 analysis of 19 cases suggest disease heterogeneity
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Takayuki Kinoshita, Nobuyoshi Hiraoka, Tomoyasu Kato, Susumu Wakai, Takashi Kubo, Akihiko Yoshida, Masaya Sekimizu, Hitoshi Ichikawa, Shun-ichi Watanabe, Masashi Fukayama, Naohiro Makise, and Akira Kawai
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Adult ,Male ,0301 basic medicine ,Jumonji Domain-Containing Histone Demethylases ,Pathology ,medicine.medical_specialty ,Extraskeletal Osteosarcoma ,Histology ,Soft Tissue Neoplasms ,Disease ,Liposarcoma ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,CDKN2A ,medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Osteosarcoma ,biology ,Osteoid ,business.industry ,Soft tissue ,Proto-Oncogene Proteins c-mdm2 ,General Medicine ,Middle Aged ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Mdm2 ,Female ,Sarcoma ,business - Abstract
Aims Extraskeletal osteosarcoma (ESOS) is a sarcoma in the non-skeletal tissue that directly produces neoplastic osteoid or bone. De-differentiated liposarcoma (DDLPS) and malignant peripheral nerve sheath tumour (MPNST) are the two most common types of sarcoma that can harbour heterologous osteosarcomatous differentiation. We aimed to determine the potential relationship of ESOS to DDLPS and MPNST. Methods and results We investigated MDM2 and H3K27me3 status in 19 cases of ESOS, two of which contained a low-grade component. The ESOS affected deep soft tissues (n = 10), superficial soft tissues (n = 3) and organs (n = 6). Among 10 deep soft-tissue ESOS, six showed MDM2 amplification, four of which also harboured CDK4 co-amplification. Both ESOS with a low-grade component showed co-amplification for MDM2 and CDK4. Among the six organ-based ESOS three giant cell-rich ESOS showed an H3K27me3 deficiency (one in primary and two in metastatic sites). Using targeted next generation sequencing, an H3K27me3-deficient ESOS showed EED homozygous deletion, while none of the three showed alterations in NF1, CDKN2A or SUZ12 genes. During median follow-up of 20 months, all six patients with MDM2-amplified ESOS lived for 3-103 months, while two of the three patients with H3K27me3-deficient ESOS died from this disease in 4 and 20 months, respectively. Conclusion We demonstrate that ESOS may include at least two small subsets: an MDM2-amplified deep soft-tissue ESOS (which may be related to DDLPS) and an H3K27me3-deficient organ-based ESOS (which is probably unrelated to MPNST). Larger studies are required to validate the present observations and investigate the clinical implications of such subcategorisation.
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- 2018
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3. Gastric pyloric gland adenoma: a multicentre clinicopathological study of 67 cases
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Ian Brown, Namrata Setia, Tetsuo Ushiku, Gregory Y. Lauwers, Amitabh Srivastava, Masato Yozu, Won-Tak Choi, Joseph Misdraji, Rish K. Pai, Ryan M. Gill, Masashi Fukayama, and Melanie Johncilla
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Adenoma ,Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Histology ,Autoimmune Gastritis ,Adenocarcinoma ,Gastroenterology ,Pathology and Forensic Medicine ,Familial adenomatous polyposis ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Immunophenotyping ,Stomach Neoplasms ,Internal medicine ,Biomarkers, Tumor ,medicine ,Genetic predisposition ,Humans ,Aged ,Aged, 80 and over ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Cell Transformation, Neoplastic ,030104 developmental biology ,Gastric Mucosa ,Dysplasia ,030220 oncology & carcinogenesis ,Disease Progression ,Immunohistochemistry ,Female ,Neoplasm Recurrence, Local ,business - Abstract
AIMS There is limited information regarding the clinicopathological and immunohistochemical characteristics of gastric pyloric gland adenomas (PGAs). METHODS AND RESULTS Sixty-seven cases of gastric PGA from 57 patients were analysed. PGAs occurred with similar frequency in men and women (47.4 and 52.6%, respectively), with a mean age of 66 years. Most presented in the gastric body/fundus (67.2%). Fifteen cases (22.4%) developed against a background of autoimmune gastritis (AIG), whereas normal mucosa was seen in 35.8%. Only 16.4% (11 cases) developed in patients with a genetic predisposition, most commonly familial adenomatous polyposis. Low-grade lesions had a mean size of 1.5 cm, while PGAs with high-grade dysplasia (HGD) or adenocarcinoma had a mean size of 3.5 cm (P < 0.001) and more commonly showed tubulovillous architecture (50.0 versus 25.6% in low-grade dysplasia; P = 0.040). Most PGAs (61.2%) co-expressed mucin (MUC)5AC and MUC6 (mixed type), which was associated significantly with HGD or adenocarcinoma (P = 0.013). AIG was also associated with HGD (P = 0.027), but genetic predisposition did not correlate with the grade of dysplasia (P = 0.793). The recurrence rate of PGA was similar for high- (11.8%) and low-grade lesions (7.4%) (P = 0.624). CONCLUSIONS The risk of HGD increases with the size of PGA, tubulovillous architecture and the presence of AIG as well as mixed immunophenotype. As the overall local recurrence rate is less than 10%, PGAs may be treated conservatively, but they should be excised completely if possible, particularly if they are large or show high-grade features.
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- 2018
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4. Claudin-18 overexpression in intestinal-type mucinous borderline tumour of the ovary
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Halimi, Sultan Ahmad, Maeda, Daichi, Shinozaki-Ushiku, Aya, Koso, Takahiro, Matsusaka, Keisuke, Tanaka, Mariko, Arimoto, Takahide, Oda, Katsutoshi, Kawana, Kei, Yano, Tetsu, Fujii, Tomoyuki, and Fukayama, Masashi
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- 2013
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5. Expression of multidrug resistance 1 gene in B-cell lymphomas: association with follicular dendritic cells
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Yagi, Keiko, Yamamoto, Kouhei, Umeda, Shigeaki, Abe, Shinya, Suzuki, Shiho, Onishi, Iichiroh, Kirimura, Susumu, Fukayama, Masashi, Arai, Ayako, Kitagawa, Masanobu, and Kurata, Morito
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- 2013
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6. Distinct expression pattern of claudin-6, a primitive phenotypic tight junction molecule, in germ cell tumours and visceral carcinomas
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Ushiku, Tetsuo, Shinozaki-Ushiku, Aya, Maeda, Daichi, Morita, Shigeki, and Fukayama, Masashi
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- 2012
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7. Gastric carcinoma with invasive micropapillary pattern and its association with lymph node metastasis
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Ushiku, Tetsuo, Matsusaka, Keisuke, Iwasaki, Yoshiaki, Tateishi, Yoko, Funata, Nobuaki, Seto, Yasuyuki, and Fukayama, Masashi
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- 2011
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8. Gastrointestinal tissue‐based molecular biomarkers: a practical categorisation based on the 2019 World Health Organization classification of epithelial digestive tumours
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Quezada‐Marín, Javier I, primary, Lam, Alfred K, additional, Ochiai, Atsushi, additional, Odze, Robert D, additional, Washington, Kay M, additional, Fukayama, Masashi, additional, Rugge, Massimo, additional, Klimstra, David S, additional, Nagtegaal, Iris D, additional, Tan, Puay‐Hoon, additional, Arends, Mark J, additional, Goldblum, John R, additional, Cree, Ian A, additional, and Salto‐Tellez, Manuel, additional
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- 2020
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9. Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer
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Morikawa, Teppei, Maeda, Daichi, Kume, Haruki, Homma, Yukio, and Fukayama, Masashi
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- 2010
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10. Hepatocellular oncofetal protein, glypican 3 is a sensitive marker for α-fetoprotein-producing gastric carcinoma
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Hishinuma, M, Ohashi, K-I, Yamauchi, N, Kashima, T, Uozaki, H, Ota, S, Kodama, T, Aburatani, H, and Fukayama, M
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- 2006
11. Cytoplasmic localization of p63 is associated with poor patient survival in lung adenocarcinoma
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Narahashi, T, Niki, T, Wang, T, Goto, A, Matsubara, D, Funata, N, and Fukayama, M
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- 2006
12. Prevalence of CD99 protein expression in pancreatic endocrine tumours (PETs)
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Goto, A, Niki, T, Terado, Y, Fukushima, J, and Fukayama, M
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- 2004
13. Intrahepatic cholangiocarcinoma frequently shows loss of BAP1 and PBRM1 expression, and demonstrates specific clinicopathological and genetic characteristics with BAP1 loss
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Norihiro Kokudo, Kiyoshi Hasegawa, Akimasa Hayashi, Masashi Fukayama, Junichi Arita, Kento Misumi, Yoshihiro Sakamoto, and Junji Shibahara
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Adult ,Male ,0301 basic medicine ,Prognostic factor ,Pathology ,medicine.medical_specialty ,Histology ,Perineural invasion ,Kaplan-Meier Estimate ,Biology ,Pathology and Forensic Medicine ,PBRM1 ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Biomarkers, Tumor ,medicine ,Humans ,Intrahepatic Cholangiocarcinoma ,Aged ,Proportional Hazards Models ,BAP1 ,Proportional hazards model ,Tumor Suppressor Proteins ,Mucin ,Nuclear Proteins ,General Medicine ,Middle Aged ,Prognosis ,Immunohistochemistry ,DNA-Binding Proteins ,030104 developmental biology ,Bile Duct Neoplasms ,030220 oncology & carcinogenesis ,Female ,Ubiquitin Thiolesterase ,Transcription Factors - Abstract
Aims BAP1 and PBRM1 expression loss has been observed in multiple cancers, including intrahepatic cholangiocarcinoma (ICC). We investigated BAP1 and PBRM1 expression in ICC using immunohistochemistry, and analyzed its association with clinicopathological and genetic features, including two histologic subtypes. Methods and results Whole-section slides of 108 consecutive primary ICC cases were immunostained against BAP1 and PBRM1. Complete loss of BAP1 and PBRM1 was observed in 21 (19.4%) and 25 (23.1%) cases, respectively, and partial loss was identified in 4 (3.7%) and 9 (8.4%) cases. In all cases, normal bile ducts were strongly and diffusely positive for both BAP1 and PBRM1. ICC with BAP1 loss showed lower serum CA19-9 levels, less perineural invasion, rare mucin production, weaker immunoreactivity against S-100P, and stronger immunoreactivity against N-cadherin and NCAM. IDH mutations were identified more frequently in ICCs with BAP1 loss. All ICC with BAP1 loss corresponded to small-duct-type ICC. Multivariate Cox regression analysis showed that BAP1 loss was an independent prognostic factor for both overall and recurrence-free survival (P < 0.05). PBRM1 loss, on the other hand, was found in both small-duct-type and large-duct-type ICC, and was not significantly associated with any specific characteristics, including prognosis. Conclusion BAP1 and PBRM1 loss is frequently seen in ICC. ICC with BAP1 loss shares features of small-duct-type ICC. This article is protected by copyright. All rights reserved.
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- 2017
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14. Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma
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Jun Nakajima, Masashi Fukayama, Aya Shinozaki-Ushiku, Tetsuo Ushiku, Masaki Anraku, and Shigeki Morita
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Adult ,Male ,Mesothelioma ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Histology ,Kaplan-Meier Estimate ,macromolecular substances ,medicine.disease_cause ,Asbestos ,Pathology and Forensic Medicine ,03 medical and health sciences ,Mesothelial hyperplasia ,0302 clinical medicine ,Biomarkers, Tumor ,Humans ,Medicine ,Enhancer of Zeste Homolog 2 Protein ,Survival analysis ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,BAP1 ,business.industry ,Tumor Suppressor Proteins ,Mesothelioma, Malignant ,EZH2 ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Female ,business ,Ubiquitin Thiolesterase - Abstract
Aims Malignant mesothelioma is a highly aggressive cancer that is usually diagnosed at advanced stages; thus, highly sensitive and specific markers are necessary for its early definitive diagnosis. The aim of this study was to evaluate the diagnostic utility and prognostic significance of BAP1 and EZH2 in malignant mesothelioma. Methods and results The expression of BAP1 and EZH2 was investigated by immunohistochemistry in 32 malignant mesotheliomas and 44 benign mesothelial proliferative lesions, including well-differentiated papillary mesothelioma (n = 4), mesothelial inclusion cyst (n = 22), and reactive mesothelial hyperplasia (n = 18). BAP1 loss and high EZH2 expression were observed in 17 (53%) and 22 (66%) malignant mesothelioma cases, respectively, whereas none of the benign lesions showed BAP1 loss or high EZH2 expression. The combination of BAP1 loss and high EZH2 expression as markers to differentiate epithelioid/biphasic malignant mesothelioma from benign mesothelial lesions was highly sensitive (90%) and specific (100%). There were no statistically significant associations between parameters such as age and sex of patients, tumour location, asbestos exposure, treatment, histology, and BAP1 or EZH2 expression. Survival analysis revealed that BAP1 loss, but not high EZH2 expression, was associated with a better prognosis. Conclusions BAP1 loss and high EZH2 expression were highly specific to malignant mesothelioma in differentiating it from benign mesothelial proliferations, and the combination of these two markers improved the diagnostic accuracy.
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- 2017
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15. Extraskeletal osteosarcoma: MDM2 and H3K27me3 analysis of 19 cases suggest disease heterogeneity
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Makise, Naohiro, primary, Sekimizu, Masaya, additional, Kubo, Takashi, additional, Wakai, Susumu, additional, Watanabe, Shun-ichi, additional, Kato, Tomoyasu, additional, Kinoshita, Takayuki, additional, Hiraoka, Nobuyoshi, additional, Fukayama, Masashi, additional, Kawai, Akira, additional, Ichikawa, Hitoshi, additional, and Yoshida, Akihiko, additional
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- 2018
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16. Gastric pyloric gland adenoma: a multicentre clinicopathological study of 67 cases
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Choi, Won-Tak, primary, Brown, Ian, additional, Ushiku, Tetsuo, additional, Yozu, Masato, additional, Setia, Namrata, additional, Srivastava, Amitabh, additional, Johncilla, Melanie, additional, Pai, Rish K, additional, Gill, Ryan M, additional, Fukayama, Masashi, additional, Misdraji, Joseph, additional, and Lauwers, Gregory Y, additional
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- 2018
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17. Expression ofmultidrug resistance 1gene in B-cell lymphomas: association with follicular dendritic cells
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Keiko Yagi, Susumu Kirimura, Masanobu Kitagawa, Iichiroh Onishi, Shinya Abe, Morito Kurata, Kouhei Yamamoto, Masashi Fukayama, Shiho Suzuki, Ayako Arai, and Shigeaki Umeda
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Pathology ,medicine.medical_specialty ,Histology ,Follicular dendritic cells ,Follicular lymphoma ,Germinal center ,General Medicine ,Biology ,medicine.disease ,Pathology and Forensic Medicine ,Lymphoma ,Raji cell ,medicine.anatomical_structure ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Cancer research ,B-cell lymphoma ,neoplasms ,Lymph node ,B cell - Abstract
Aims: Multidrug resistance (MDR) in B-cell lymphomas still constitutes a major obstacle to the effectiveness of chemotherapy even in the anti-CD20 antibody therapy era. The aim of this study was to investigate the expression of MDR-associated molecules in reactive lymphadenopathy (RL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Methods and results: The expression of mRNA for ABC-transporter family genes was determined by real-time RT-PCR in lymph nodes from RL, FL, and DLBCL cases. MDR1 exhibited significantly stronger expression in RL, FL, and DLBCL than Raji B-cell lymphoma cells. RL and FL showed significantly higher expression than DLBCL. Immunohistochemically, MDR1 positive cells were localized in the germinal centers of RL and center of the nodular lesions of FL showing associations with CD21 positive follicular dendritic cells (FDCs). Raji cells were co-cultured with FDC sarcoma-derived cells and the expression of MDR1 and drug resistance were analyzed. The co-culture of Raji cells with FDCs induced strong expression of MDR1 and introduced resistance to doxorubicin-induced apoptosis. Conclusions: These results suggest that FDCs induce MDR1 expression in reactive as well as neoplastic B-cells. Inhibition of the interaction of FDCs with B-cells may provide a novel strategy for treating the chemotherapy resistant fraction.
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- 2013
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18. Distinct expression pattern of claudin-6, a primitive phenotypic tight junction molecule, in germ cell tumours and visceral carcinomas
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Aya Shinozaki-Ushiku, Shigeki Morita, Tetsuo Ushiku, Daichi Maeda, and Masashi Fukayama
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medicine.medical_specialty ,Pathology ,Histology ,Tissue microarray ,endocrine system diseases ,Fetal adenocarcinoma ,General Medicine ,Biology ,urologic and male genital diseases ,medicine.disease ,female genital diseases and pregnancy complications ,digestive system diseases ,Pathology and Forensic Medicine ,medicine.anatomical_structure ,medicine ,Carcinoma ,Immunohistochemistry ,Histopathology ,Yolk sac ,Claudin ,Germ cell - Abstract
Ushiku T, Shinozaki-Ushiku A, Maeda D, Morita S & Fukayama M (2012) Histopathology Distinct expression pattern of claudin-6, a primitive phenotypic tight junction molecule, in germ cell tumours and visceral carcinomas Aims: This study aimed to clarify claudin-6 expression patterns in cancers. Methods and results: We surveyed claudin-6 expression by immunohistochemistry using tissue microarray in 860 tumours, including germ cell tumours and major carcinomas. Claudin-6 was expressed consistently in germ cell tumours (28 of 28, 100%), whereas only 64 (8%) of 832 non-germ cell tumours demonstrated claudin-6 expression. Further immunohistochemical study in full tissue sections demonstrated diffuse claudin-6 staining in all seminomas (n = 14), embryonal carcinomas (n = 10), yolk sac tumours (n = 12) and mononuclear trophoblastic cells of choriocarcinomas (n = 3), and focal staining in immature epithelial components of immature teratomas (n = 6). Additionally, because alpha-fetoprotein (AFP)-producing gastric adenocarcinomas and pulmonary high-grade fetal adenocarcinomas were among the claudin-6 expressing non-germ cell tumours in the microarray studies, we predicted that claudin-6 may be a biomarker for them and studied additional tumours in full sections, which showed claudin-6 expression in AFP-producing gastric adenocarcinomas (18 of 20, 90%) and pulmonary high-grade fetal adenocarcinomas (four of five, 80%). Only one of 11 hepatoblastomas demonstrated focal claudin-6 staining. Conclusions: This study demonstrated that claudin-6 is a novel diagnostic marker for primitive germ cell tumours and is also expressed frequently in some cancers with a primitive phenotype.
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- 2012
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19. Gastric carcinoma with invasive micropapillary pattern and its association with lymph node metastasis
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Keisuke Matsusaka, Tetsuo Ushiku, Yoko Tateishi, Masashi Fukayama, Yasuyuki Seto, Yoshiaki Iwasaki, and Nobuaki Funata
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Pathology ,medicine.medical_specialty ,Histology ,business.industry ,Lymphovascular invasion ,Stomach ,General Medicine ,medicine.disease ,Pathology and Forensic Medicine ,medicine.anatomical_structure ,Papillary adenocarcinoma ,Lymphatic system ,Submucosa ,medicine ,Carcinoma ,Adenocarcinoma ,Immunohistochemistry ,business - Abstract
Ushiku T, Matsusaka K, Iwasaki Y, Tateishi Y, Funata N, Seto Y & Fukayama M (2011) Histopathology 59, 1081–1089 Gastric carcinoma with invasive micropapillary pattern and its association with lymph node metastasis Aims: This study aimed to characterize the clinicopathological features of invasive micropapillary carcinoma (IMPC) of the stomach. Methods and results: Seventeen cases of gastric IMPC were identified from histological reviews of 1178 consecutive cases. IMPC components occupied 10–90% of the entire tumours. Fifteen tumours showed invasion into the muscularis propria or deeper, whereas two tumours were limited to the submucosa. All 17 cases were associated with tubular or papillary adenocarcinoma. Lymphatic and venous invasion were identified more frequently in cases with IMPC components than in those without (P = 0.0023 and P = 0.0009, respectively). Nodal metastases were identified in 14 of 17 (82%) cases with IMPC components, whereas they were detected in 540 of 1161 (47%) cases with no IMPC components (P = 0.0053). Multivariate analysis demonstrated that the presence of IMPC was an independent predictor of nodal metastasis. Conclusions: Conservative treatments, such as endoscopic resection, should not be used for gastric carcinoma with IMPC components, as these cases are associated with a high propensity for lymphovascular invasion and nodal metastasis.
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- 2011
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20. Utility of ATRX immunohistochemistry in diagnosis of adult diffuse gliomas
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Akitake Mukasa, Masako Ikemura, Nobuhito Saito, Shunsaku Takayanagi, Junji Shibahara, Masashi Fukayama, Hiroyuki Aburatani, and Koki Aihara
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P53 overexpression ,Adult ,Male ,Pathology ,medicine.medical_specialty ,X-linked Nuclear Protein ,Histology ,IDH1 ,Concordance ,Oligodendroglioma ,Biology ,Astrocytoma ,Tp53 mutation ,medicine.disease_cause ,Pathology and Forensic Medicine ,03 medical and health sciences ,Diffuse Glioma ,Young Adult ,0302 clinical medicine ,medicine ,Humans ,neoplasms ,ATRX ,Aged ,Aged, 80 and over ,Mutation ,DNA Helicases ,Nuclear Proteins ,General Medicine ,Glioma ,Middle Aged ,Immunohistochemistry ,Isocitrate Dehydrogenase ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Neoplasm Grading ,Tumor Suppressor Protein p53 ,Glioblastoma ,030217 neurology & neurosurgery - Abstract
Aims We performed an immunohistochemical analysis of alpha-thalassaemia/mental retardation syndrome X-linked (ATRX) expression in adult diffuse gliomas, with reference to clinicopathological and genetic features, to determine the utility of this analysis in diagnostic practice. Methods and results A total of 193 adult diffuse gliomas underwent immunohistochemical analysis. In areas in which internal controls, neurones, glia and blood vessels were properly stained, the ATRX immunoreactivity of tumour cells was either almost totally absent or completely retained in all cases. There was perfect concordance between the immunohistochemical results and ATRX mutation status, which was known in 19 cases. ATRX loss was observed in 54.5, 30.8 and 0.0% of grades II/III astrocytomas, oligoastrocytomas and oligodendrogliomas, respectively, and 12.7% of glioblastomas. In grades II/III gliomas, most ATRX-loss cases (92.3%) had IDH1/2 mutations. ATRX loss was associated significantly with TP53 mutation and p53 overexpression (P < 0.001), but was never accompanied by 1p/19q co-deletion. IDH1/2 mutation in ATRX-loss tumours was less frequent in glioblastomas than in grades II/III gliomas (P < 0.001). Further, there was no significant association between ATRX loss and p53 overexpression in glioblastomas. ATRX-loss glioblastomas affected younger patients (P < 0.001) and occurred more frequently in locations other than the cerebral hemispheres (P = 0.006). Most grades II/III gliomas (93.3%) were categorized into three molecular subtypes based on the status of IDH1/2 mutation, ATRX immunohistochemistry and 1p/19q co-deletion. Conclusions Distinct histological and molecular characteristics of adult diffuse gliomas with and without ATRX immunoreactivity indicate the utility of ATRX immunohistochemistry in diagnostic practice.
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- 2015
21. Cytoplasmic localization of p63 is associated with poor patient survival in lung adenocarcinoma
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T Wang, Akiteru Goto, Nobuaki Funata, Masashi Fukayama, Daisuke Matsubara, T Narahashi, and Toshiro Niki
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Adult ,Male ,Cytoplasm ,medicine.medical_specialty ,Pathology ,Lung Neoplasms ,Histology ,Blotting, Western ,Adenocarcinoma ,Pathology and Forensic Medicine ,Biomarkers, Tumor ,Adenocarcinoma of the lung ,medicine ,Humans ,Lung cancer ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Cell Nucleus ,Lung ,integumentary system ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Respiratory disease ,Membrane Proteins ,Anatomical pathology ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Survival Analysis ,stomatognathic diseases ,Ki-67 Antigen ,medicine.anatomical_structure ,Female ,sense organs ,Tumor Suppressor Protein p53 ,business - Abstract
Aims : To determine the significance of p63 protein expression in the development and progression of lung adenocarcinoma. Mehods and results : The expression of p63 was immunohistochemically investigated in 92 cases of lung adenocarcinoma with a maximum diameter of 30 mm or less. p63 expression was observed not only in the nuclei (46/92 cases, 50%), but also in the cytoplasm of neoplastic cells (47/92, 51%). Nuclear localization of p63 was correlated with nuclear accumulation of p53 (P = 0.0120), whereas the presence of nuclear p63 had no apparent effect on patient survival. Cytoplasmic localization of p63 was found to be correlated with shorter survival periods by univariate and multivariate analyses (P = 0.0486 and P = 0.0488, respectively) and the relation was independent of clinicopathological factors. Cytoplasmic localization of p63 was further confirmed by immunoblots of the cytoplasmic fraction of HLC-1, a lung adenocarcinoma cell line which predominately expressed ΔNp63α transcript relative to TAp63 transcript by quantitative reverse transcriptase-polymerase chain reaction. Conclusions : Cytoplasmic expression of p63 is an adverse prognostic factor in patients with adenocarcinoma of the lung.
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- 2006
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22. Intrahepatic cholangiocarcinoma frequently shows loss of BAP1 and PBRM1 expression, and demonstrates specific clinicopathological and genetic characteristics with BAP1 loss
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Misumi, Kento, primary, Hayashi, Akimasa, additional, Shibahara, Junji, additional, Arita, Junichi, additional, Sakamoto, Yoshihiro, additional, Hasegawa, Kiyoshi, additional, Kokudo, Norihiro, additional, and Fukayama, Masashi, additional
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- 2017
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23. Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma
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Shinozaki-Ushiku, Aya, primary, Ushiku, Tetsuo, additional, Morita, Shigeki, additional, Anraku, Masaki, additional, Nakajima, Jun, additional, and Fukayama, Masashi, additional
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- 2017
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24. Hepatocellular carcinoma with steatohepatitic features: a clinicopathological study of Japanese patients
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Masashi Fukayama, Norihiro Kokudo, Yoshihiro Sakamoto, Junji Shibahara, and Sumiyo Ando
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Adult ,Male ,medicine.medical_specialty ,Pathology ,Histology ,Carcinoma, Hepatocellular ,Hepatitis C virus ,medicine.disease_cause ,Gastroenterology ,Pathology and Forensic Medicine ,Cohort Studies ,Young Adult ,Japan ,Diabetes mellitus ,Internal medicine ,Medicine ,Humans ,neoplasms ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Bile duct ,Liver Neoplasms ,General Medicine ,HCCS ,Middle Aged ,medicine.disease ,Prognosis ,digestive system diseases ,Fatty Liver ,medicine.anatomical_structure ,Liver ,Hepatocellular carcinoma ,Female ,Steatohepatitis ,Metabolic syndrome ,Steatosis ,business - Abstract
Aims The aim of this study was to investigate the clinicopathological significance of steatohepatitic features in hepatocellular carcinomas (HCCs) using a large-scale analysis. Methods and results Retrospective clinicopathological analysis was performed on HCCs treated surgically at the University of Tokyo Hospital between 2005 and 2010. The diagnosis of HCC with steatohepatitic features (SH-HCC) was made if the tumour fulfilled four of the following five criteria: steatosis (>5% tumour cells), ballooning or Mallory–Denk body formation, interstitial fibrosis and inflammatory infiltrates. There were 120 HCCs (31.4%) from 106 patients (36.3%) that met the criteria of SH-HCC. Patients with SH-HCC were characterized by a higher frequency of diabetes mellitus and hypertension, along with higher serum levels of cholesterol and triglycerides, than those with conventional HCC (P
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- 2013
25. Claudin-18 overexpression in intestinal-type mucinous borderline tumour of the ovary
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Tetsu Yano, Masashi Fukayama, Daichi Maeda, Katsutoshi Oda, Kei Kawana, Tomoyuki Fujii, Sultan Ahmad Halimi, Takahide Arimoto, Takahiro Koso, Aya Shinozaki-Ushiku, Keisuke Matsusaka, and Mariko Tanaka
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Pathology ,medicine.medical_specialty ,Histology ,Vimentin ,Ovary ,Cystadenocarcinoma, Mucinous ,Pathology and Forensic Medicine ,Cystadenoma, Mucinous ,Progesterone receptor ,medicine ,Biomarkers, Tumor ,Cluster Analysis ,Humans ,CDX2 ,Claudin ,Ovarian Neoplasms ,biology ,General Medicine ,Immunohistochemistry ,digestive system diseases ,Epithelium ,Serous fluid ,medicine.anatomical_structure ,Claudins ,biology.protein ,Female - Abstract
Aims Mucinous borderline tumours of the ovary are subclassified as intestinal-type (IMBT) and endocervical-like (EMBT), which differ in their clinicopathological features. In this study, we attempted to elucidate characteristics of the mucinous epithelium in each subtype. Methods and results The expression of claudin-18, a marker of gastric differentiation, MUCs, CDX2, CK7, CK20, oestrogen receptor (ER), progesterone receptor (PgR), CA-125 and vimentin in IMBTs (n = 54), EMBTs (n = 25) and serous borderline tumours (SBTs) (n = 22) were compared by immunohistochemistry. Claudin-18 positivity was identified in 98% of the IMBTs, whereas only 4% of the EMBTs were claudin-18-positive. Expression of intestinal markers such as CDX2 and MUC2 was relatively infrequent in IMBTs (48% and 33%, respectively). Mullerian-lineage markers such as ER, PgR and vimentin were expressed rarely in IMBTs, while most EMBTs and SBTs were positive for these markers. Hierarchial clustering revealed a close association between EMBTs and SBTs, while IMBTs were clearly separate. Conclusions Claudin-18 positivity is a specific phenotype that is characteristic of IMBTs. Frequent and diffuse expression of gastric markers, along with less frequent and usually focal expression of intestinal markers, suggests that IMBTs are essentially composed of gastrointestinal-type mucinous epithelium (gastric-type epithelium with a variable degree of intestinal differentiation).
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- 2013
26. Expression of multidrug resistance 1 gene in B-cell lymphomas: association with follicular dendritic cells
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Keiko, Yagi, Kouhei, Yamamoto, Shigeaki, Umeda, Shinya, Abe, Shiho, Suzuki, Iichiroh, Onishi, Susumu, Kirimura, Masashi, Fukayama, Ayako, Arai, Masanobu, Kitagawa, and Morito, Kurata
- Subjects
B-Lymphocytes ,Lymphoma, B-Cell ,Reverse Transcriptase Polymerase Chain Reaction ,Apoptosis ,Real-Time Polymerase Chain Reaction ,Immunohistochemistry ,Coculture Techniques ,Drug Resistance, Multiple ,Drug Resistance, Neoplasm ,Cell Line, Tumor ,Humans ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,RNA, Messenger ,Dendritic Cells, Follicular - Abstract
Multidrug resistance (MDR) in B-cell lymphomas still constitutes a major obstacle to the effectiveness of chemotherapy even in the anti-CD20 antibody therapy era. The aim of this study was to investigate the expression of MDR-associated molecules in reactive lymphadenopathy (RL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). The expression of mRNA for ABC-transporter family genes was determined by real-time RT-PCR in lymph nodes from RL, FL, and DLBCL cases. MDR1 exhibited significantly stronger expression in RL, FL, and DLBCL than Raji B-cell lymphoma cells. RL and FL showed significantly higher expression than DLBCL. Immunohistochemically, MDR1 positive cells were localized in the germinal centers of RL and center of the nodular lesions of FL showing associations with CD21 positive follicular dendritic cells (FDCs). Raji cells were co-cultured with FDC sarcoma-derived cells and the expression of MDR1 and drug resistance were analyzed. The co-culture of Raji cells with FDCs induced strong expression of MDR1 and introduced resistance to doxorubicin-induced apoptosis. These results suggest that FDCs induce MDR1 expression in reactive as well as neoplastic B-cells. Inhibition of the interaction of FDCs with B-cells may provide a novel strategy for treating the chemotherapy resistant fraction.
- Published
- 2013
27. Distinct expression pattern of claudin-6, a primitive phenotypic tight junction molecule, in germ cell tumours and visceral carcinomas
- Author
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Tetsuo, Ushiku, Aya, Shinozaki-Ushiku, Daichi, Maeda, Shigeki, Morita, and Masashi, Fukayama
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Male ,Lung Neoplasms ,Endodermal Sinus Tumor ,Adenocarcinoma ,Neoplasms, Germ Cell and Embryonal ,Seminoma ,Tight Junctions ,Fetus ,Phenotype ,Testicular Neoplasms ,Stomach Neoplasms ,Carcinoma, Embryonal ,Claudins ,Biomarkers, Tumor ,Humans ,Female ,alpha-Fetoproteins - Abstract
This study aimed to clarify claudin-6 expression patterns in cancers.We surveyed claudin-6 expression by immunohistochemistry using tissue microarray in 860 tumours, including germ cell tumours and major carcinomas. Claudin-6 was expressed consistently in germ cell tumours (28 of 28, 100%), whereas only 64 (8%) of 832 non-germ cell tumours demonstrated claudin-6 expression. Further immunohistochemical study in full tissue sections demonstrated diffuse claudin-6 staining in all seminomas (n=14), embryonal carcinomas (n=10), yolk sac tumours (n=12) and mononuclear trophoblastic cells of choriocarcinomas (n=3), and focal staining in immature epithelial components of immature teratomas (n=6). Additionally, because alpha-fetoprotein (AFP)-producing gastric adenocarcinomas and pulmonary high-grade fetal adenocarcinomas were among the claudin-6 expressing non-germ cell tumours in the microarray studies, we predicted that claudin-6 may be a biomarker for them and studied additional tumours in full sections, which showed claudin-6 expression in AFP-producing gastric adenocarcinomas (18 of 20, 90%) and pulmonary high-grade fetal adenocarcinomas (four of five, 80%). Only one of 11 hepatoblastomas demonstrated focal claudin-6 staining.This study demonstrated that claudin-6 is a novel diagnostic marker for primitive germ cell tumours and is also expressed frequently in some cancers with a primitive phenotype.
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- 2012
28. Gastric carcinoma with invasive micropapillary pattern and its association with lymph node metastasis
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Tetsuo, Ushiku, Keisuke, Matsusaka, Yoshiaki, Iwasaki, Yoko, Tateishi, Nobuaki, Funata, Yasuyuki, Seto, and Masashi, Fukayama
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Aged, 80 and over ,Male ,Stomach Neoplasms ,Lymphatic Metastasis ,Biomarkers, Tumor ,Humans ,Female ,Adenocarcinoma ,Middle Aged ,Neoplasm Grading ,Immunohistochemistry ,Carcinoma, Papillary ,Aged - Abstract
This study aimed to characterize the clinicopathological features of invasive micropapillary carcinoma (IMPC) of the stomach.Seventeen cases of gastric IMPC were identified from histological reviews of 1178 consecutive cases. IMPC components occupied 10-90% of the entire tumours. Fifteen tumours showed invasion into the muscularis propria or deeper, whereas two tumours were limited to the submucosa. All 17 cases were associated with tubular or papillary adenocarcinoma. Lymphatic and venous invasion were identified more frequently in cases with IMPC components than in those without (P = 0.0023 and P = 0.0009, respectively). Nodal metastases were identified in 14 of 17 (82%) cases with IMPC components, whereas they were detected in 540 of 1161 (47%) cases with no IMPC components (P = 0.0053). Multivariate analysis demonstrated that the presence of IMPC was an independent predictor of nodal metastasis.Conservative treatments, such as endoscopic resection, should not be used for gastric carcinoma with IMPC components, as these cases are associated with a high propensity for lymphovascular invasion and nodal metastasis.
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- 2011
29. Utility of ATRX immunohistochemistry in diagnosis of adult diffuse gliomas
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Ikemura, Masako, primary, Shibahara, Junji, additional, Mukasa, Akitake, additional, Takayanagi, Shunsaku, additional, Aihara, Koki, additional, Saito, Nobuhito, additional, Aburatani, Hiroyuki, additional, and Fukayama, Masashi, additional
- Published
- 2016
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30. Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer
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Teppei, Morikawa, Daichi, Maeda, Haruki, Kume, Yukio, Homma, and Masashi, Fukayama
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Male ,Ribonucleoside Diphosphate Reductase ,Blotting, Western ,Middle Aged ,Immunohistochemistry ,Urinary Bladder Neoplasms ,Tissue Array Analysis ,Cell Line, Tumor ,Lymphatic Metastasis ,Biomarkers, Tumor ,Carcinoma, Squamous Cell ,Tumor Cells, Cultured ,Humans ,Female ,RNA, Small Interfering ,Urothelium ,Aged - Abstract
To examine the immunohistochemical expression and function of ribonucleotide reductase M2 subunit (RRM2), a gemcitabine-related molecule, in bladder cancer.One hundred and seventeen bladder specimens on a tissue microarray were immunostained for RRM2. Positive RRM2 staining was observed in none of 14 examples of non-neoplastic urothelium, none of four low-grade urothelial carcinoma (UC), 69 of 83 (83%) high-grade UC, three of three (100%) squamous cell carcinoma and 12 of 13 (92%) lymph node metastasis of UC. RRM2 overexpression was associated significantly with muscularis propria invasion in UC patients who had undergone radical cystectomy (P=0.005). Immunohistochemistry for RRM2 was then applied to small biopsy specimens of 15 cystitis with reactive atypia cases and 25 urothelial carcinoma in-situ (CIS) cases. Positive RRM2 staining was found in one of 15 (6.7%) cystitis with reactive atypia cases and in 24 of 25 (96%) CIS cases. Finally, UM-UC-3 bladder cancer cells were transfected with RRM2 siRNAs and cell growth was evaluated. Knockdown of RRM2 protein markedly inhibited cell growth.We have shown frequent overexpression of RRM2 protein and its possible role in bladder cancer. Our results suggest that RRM2 is a novel diagnostic marker and a potential therapeutic target in bladder cancer.
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- 2010
31. Hepatocellular oncofetal protein, glypican 3 is a sensitive marker for alpha-fetoprotein-producing gastric carcinoma
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Naoko Yamauchi, Michiyo Hishinuma, Satoshi Ota, Tatsuhiko Kodama, Takeshi Kashima, Hiroshi Uozaki, Hiroyuki Aburatani, Masashi Fukayama, and Kenichi Ohashi
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Adult ,Male ,medicine.medical_specialty ,Pathology ,Histology ,Biology ,Adenocarcinoma ,Glypican 3 ,Pathology and Forensic Medicine ,Glypicans ,Stomach Neoplasms ,medicine ,Biomarkers, Tumor ,Humans ,Aged ,Aged, 80 and over ,Tissue microarray ,Anatomical pathology ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,digestive system diseases ,medicine.anatomical_structure ,Tissue Array Analysis ,Hepatocyte ,Female ,alpha-Fetoproteins ,Alpha-fetoprotein ,Oncofetal antigen - Abstract
Aims Glypican 3 (GPC3) is a cell surface heparan sulphate proteoglycan expressed specifically in the fetal liver and malignant neoplasms of hepatocyte lineage. The aim was to evaluate the significance of GPC3 in alpha-fetoprotein (AFP)-producing gastric carcinoma (GC) and other forms of GC. Methods and results We immunohistochemically evaluated GPC3 expression in representative cases of AFP-producing GC and in a tissue microarray of a consecutive series of GCs with other markers of hepatocyte lineage (AFP, PIVKA-II and hepatocyte antigen, HEP). In a series of 10 cases of AFP-producing GC, we observed immunohistochemical positivity for GPC3, PIVKA-II and HEP in 10, three and three cases in components with a hepatoid pattern and in nine, two and five cases in components with a non-hepatoid pattern, respectively. In a series of 118 cases of GC, we observed positivity for AFP, GPC3, PIVKA-II and HEP in one (0.8%), four (3.4%), six (5.1%) and 26 cases (22%), respectively. GPC3 was observed concurrently with AFP and discordantly with PIVKA-II and HEP. GPC3 positivity was clearly stronger in a larger area compared with immunoreactivity for AFP. Conclusions GPC3 is a sensitive marker for AFP-producing GC and its hepatoid component and is therefore useful to identify this aggressive subgroup of GC.
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- 2006
32. Prevalence of CD99 protein expression in pancreatic endocrine tumours (PETs)
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Y Terado, J Fukushima, Masashi Fukayama, Toshiro Niki, and Akiteru Goto
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Adult ,Male ,medicine.medical_specialty ,Pathology ,Histology ,CD99 ,Biology ,12E7 Antigen ,Pathology and Forensic Medicine ,Metastasis ,Antigens, CD ,medicine ,Acinar cell ,Biomarkers, Tumor ,Multiple Endocrine Neoplasia Type 1 ,Prevalence ,Endocrine system ,Humans ,Neoplasm Invasiveness ,Neoplasms, Glandular and Epithelial ,Anatomical pathology ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Immunohistochemistry ,Pancreatic Neoplasms ,Neuroendocrine Tumors ,medicine.anatomical_structure ,Lymphatic system ,Ki-67 Antigen ,Lymphatic Metastasis ,Female ,Pancreas ,Cell Adhesion Molecules - Abstract
Aims : To determine the prevalence of CD99 expression in pancreatic endocrine tumours (PETs). We evaluated CD99 expression and analysed Ki67 labelling by immunohistochemistry in PETs. Methods and results : Thirty-eight PETs from 33 patients were analysed. CD99 immunoreactivity was consistently observed in normal islets of the pancreas, regardless of the cell type. Tumours comprising more than 30% CD99+ cells were defined as positively immunoreactive for CD99. CD99 expression was observed in 20 of the 38 PETs examined, but not in any of the pancreatic tumours of other histological subtypes (10 ductal adenocarcinomas, five intraductal papillary-mucinous tumours, and two acinar cell tumours). Loss of CD99 expression was related to markers of worse prognosis for PET, including gross local invasion, metastasis to the lymph nodes or other organs, lymphatic or blood vessel invasion, and neuroendocrine carcinoma (NEC). Thus, CD99 expression may have an efficiency comparable to that of high Ki67 labelling index (5% or more) for prognostication. Conslusions : CD99 expression was observed frequently and exclusively in PETs, and loss of CD99 expression in PETs was found to be associated with ominous prognostic indicators.
- Published
- 2004
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