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Mesothelioma Research

Being Pathology department, we are devoting our times for the accurate pathological diagnosis and aiming as one of the pioneer Research Center for Pathobiological Understanding of Malignant Mesothelioma

Pathological diagnosis of malignant mesothelioma

Malignant mesothelioma show diverse histopathological features, making it more difficult to make accurate diagnosis or differentiating from other cancers. The use of immunohistochemical technique has improved the accuracy of pathological diagnosis in many of cases. However, there are still no proper conscience among the pathologists with expertise in mesothelioma diagnosis in some of the difficult cases (False Negative or False positive) with recent immunohistochemical data interpretations.

In Japan, we found about 15% of misdiagnosis of malignant mesothelioma (Takeshima et al., Lung Cancer, 66(2) : 191-197, 2009) by general pathologists. To improve the accuracy of pathological diagnosis of malignant mesothelioma even by general pathologists who are not expert in mesothelioma diagnosis, search of better immunohistochemical markers are essential.

mesothelioma pathologyGross, cytological, histological and immunohistochemical features
see our publications

Microarray profiling and functional analysis of malignant mesothelioma

Differential microRNA expression profiling of mesothelioma and expression analysis of miR-1 and miR-214 in mesothelioma.

Malignant mesothelioma is a highly aggressive cancer with poor prognosis and refractory to currently available therapies. Most of the patients with advanced invasive nature are not amenable to surgical resection and/or available anticancer therapy, thus development of novel effective therapeutic regimes is needed. Aberrant expression of microRNAs (miRNAs) has been proposed to contribute to carcinogenesis and aggressiveness of mesothelioma. We analyzed miRNA expression in mesothelioma cell lines using TaqMan miRNA expression array and found significant number of miRNAs, which showed increased or lost expression. We validated the increased expression of miR-182, and miR-183 in mesothelioma cell lines by individual miRNA assays and SmartFlare miRNA probes. We further investigated the miR-1, and miR-214, which were not expressed in mesothelioma cells by real-time RT-PCR. Transfection of mesothelioma cells, ACC-Meso-1 and CRL5915, with miRNA mimic (hsa-miR-1 mimic and hsa-miR-214 mimic) led to inhibition of cell growth, invasion and migration. We paid attention to PIM1, the target gene of both miR-1 and miR-214 miRNAs and which was found overexpressed in mesothelioma cells, and miR-1 and miR-214 mimic transfection of mesothelioma cell lines showed downregulation of PIM1 by western blot analysis. The miRNAs, miR-1 and miR-214, may play a role in carcinogenesis of mesothelioma thus might be considered as candidate therapeutic targets in mesothelioma.

mesotheliomna pathology

Asbestos exposure as a cause of various cancer

Malignant mesothelioma is an aggressive cancer arising from mesothelial lining of pleura, peritoneum, pericardium, and tunica vaginalis. Asbestos exposure is considered as a principal cause of malignant mesothelioma.

In Japan, the incidence of malignant mesothelioma is increasing year by year and have reached more than 1400 death per year. Many of these patients had history of occupational exposure of asbestos (80~90%) and others areconsidered due to environmental exposure (e.g. residence near asbestos factory).

mesotheliomna pathology

Our Publications on Mesothelioma

Other Research of our Department

Previous Researches of Lung Cancer


The p53 mutational frequency in the MG-exposed cases is similar to the non-exposed controls and the usual smoking-related lung cancers reported previously. However, the distinctive double mutations (G:C to A:T transition) observed in two cases are unusual and may be related to MG exposure.

p53 mutations in lung cancers from Japanese mustards gas workers.
Takeshima Y, Inai K, Bennett WP, Metcalf RA, Welsh JA, Yonehara S, Hayashi Y, Fujihara M, Yamakido M, Akiyama M, Tokuoka S, Land CE, and Harris CC.
Carcinogenesis (1994) 15 (10): 2075-2079.


The P53 mutations A-BOMB survivors were predominantly transitions (all G:C to A:T) and no G:C to T:A transversions. By contrast, lung cancers from 77 Japanese smokers have a predominance of G:C to T:A transversions.

p53 mutations in lung cancers from non-smoking atomic-bomb survivors.
Takeshima Y, Seyama T, Bennett WP, Akiyama M, Tokuoka S, Inai K, Mabuchi K, Land CE, Harris CC.
Lancet. 1993 Dec 18-25;342(8886-8887):1520-1.

P53 mutation & 3p, 9p, 17pLOH in Precancerous lesion of LUNG

Evaluation of p53 gene mutation and loss of heterozygosity of 3p, 9p and 17p in precancerous lesions of 29 lung cancer patients.
Nishisaka T, Takeshima Y, Inai K.
Hiroshima J Med Sci. 2000 Jun;49(2):109-16.

Multistep Carcinogenesis of Lung adenocarcinoma

Lung cancer has been increasing rapidly in recent years. The peripheral-type adenocarcinomashowe progression from AAH ( atypical adenomatous hyperplasia ) → BAC ( bronchioles alveolar epithelial carcinoma ) → invasive adenocarcinoma with abnormal accumulation of genetic changes.

Evaluation of p53 gene mutation and loss of heterozygosity of 3p, 9p and 17p in precancerous lesions of 29 lung cancer patients.
Takeshima Y, Yamasaki M, Nishisaka T, Kitaguchi S, Inai K.
Carcinogenesis. 1998 Oct;19(10):1755-61.
Down-regulation of KAI1 messenger RNA expression is not associated with loss of heterozygosity of the KAI1 gene region in lung adenocarcinoma.
Tagawa K, Arihiro K, Takeshima Y, Hiyama E, Yamasaki M, Inai K.
Jpn J Cancer Res. 1999 Sep;90(9):970-6.
Correlation between genetic alterations and histopathological subtypes in bronchiolo-alveolar carcinoma and atypical adenomatous hyperplasia of the lung.
Yamasaki M, Takeshima Y, Fujii S, Kitaguchi S, Matsuura M, Tagawa K, Inai K.
Pathol Int. 2000 Oct;50(10):778-85.
p21WAF1/CIP1 expression in primary lung adenocarcinomas: heterogeneous expression in tumor tissues and correlation with p53 expression and proliferative activities.
Takeshima Y, Yamasaki M, Nishisaka T, Kitaguchi S, Inai K.
Carcinogenesis. 1998 Oct;19(10):1755-61.
Correlation between morphological heterogeneity and genetic alteration within one tumor in adenocarcinomas of the lung.
Yamasaki M1, Takeshima Y, Fujii S, Matsuura M, Tagawa K, Inai K.
Pathol Int. 2000 Nov;50(11):891-6.
Expression of MUC1, MUC2, MUC5AC, and MUC6 in atypical adenomatous hyperplasia, bronchioloalveolar carcinoma, adenocarcinoma with mixed subtypes, and mucinous bronchioloalveolar carcinoma of the lung.
Awaya H, Takeshima Y, Yamasaki M, Inai K.
Am J Clin Pathol. 2004 May;121(5):644-53.
Loss of expression of E-cadherin and beta-catenin is associated with progression of pulmonary adenocarcinoma.
Awaya H, Takeshima Y, Amatya VJ, Ishida H, Yamasaki M, Kohno N, Inai K.
Pathol Int. 2005 Jan;55(1):14-8.

Abberant methylation of tumor suprresor genes in lung adenocarcinoma & squamous cell carcinoma

Inactivation of the p16 gene by hypermethylation and loss of heterozygosity in adenocarcinoma of the lung.
Awaya H, Takeshima Y, Amatya VJ, Furonaka O, Tagawa K, Kohno N, Inai K.
Pathol Int. 2004 Jul;54(7):486-9.
Aberrant methylation of p14(ARF), p15(INK4b) and p16(INK4a) genes and location of the primary site in pulmonary squamous cell carcinoma.
Furonaka O, Takeshima Y, Awaya H, Ishida H, Kohno N, Inai K.
Pathol Int. 2004 Aug;54(8):549-55.
Aberrant methylation and loss of expression of O-methylguanine-DNA methyltransferase in pulmonary squamous cell carcinoma and adenocarcinoma.
Furonaka O, Takeshima Y, Awaya H, Kushitani K, Kohno N, Inai K.
Pathol Int. 2005 Jun;55(6):303-9.

Faculty Members

Professor of Department of Pathology

Yukio Takeshima

Professor & Head of Department HU profile icon Facebook
Lecturer of Department of Pathology

Vishwa J. Amatya

Associate Professor/Leturer HU profile icon Facebook Linkedin
Assistant Professor in Department of Pathology

Kei Kushitani

Assistant Professor HU profile icon

PhD Students

PhD Student


PhD Student
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PhD Student
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MD PhD Student

Clinical Professors

Mayumi Kaneko

Department of Pathology,
Hiroshima City Asa Hospital, Hiroshima

Past Members











Masatsugu Kuraoka


Amany Sayed Mawas


Practice for Medical Research

Medical Students 2024

Hayama Soichiro

Medical Students 2023

Ono Hiroki
Okada Shogo

Medical Students 2021

Koichi Takeda

Medical Students 2020

Ihiro Endo
Yoshifumi Sakurai

Medical Students 2019

Takahiro Nomura
Masatoshi Fukuya

Medical Students 2018

Yutaro Fujii
Takuya Aikawa

Medical Students 2017

Imura Yusuke
Yano Daisuke

Medical Students 2016

Rui Suzuki
Shin Miyahara
Ikuko Ohoka

Medical Students 2015

Yasuko Okada
Katayama Yuya
Gurita Tomoyuki
Takagi Yuki

Medical Students 2014

Satoki Morita
Yuuki Naito
Hiroto Shimajiri

Medical Students 2013

Hiroyuki Aiba
Yuusuke Takahashi

Medical Students 2012

Yosuke Kagawa
Toshiwo Min
Yuta Kuhara

Contact Us

Department of Pathology
Graduate School of Biomendical & Health Sciences
Hiroshima University
 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, JAPAN
 (International: +81) 82-257-5152
 (+81) 82-257-5154
広島大学大学院 医系科学研究科
広島大学大学院 医系科学研究科 病理学研究室
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by Vishwa J. Amatya