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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 diffcult to make accurate diagnosis or differentiating from other cancers. The use of immunohisotchemical technique has improved the accuracy of pathological diagnosis in many of cases. Howerver, 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 mesthelioma diagnosis, search of better immunohistochemical markers are essential.

mesotheliomna 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

miR-182 and miR-183 promote cell proliferation and invasion by targeting FOXO1 in mesothelioma
Suzuki R, Amatya VJ, Kushitani K, Kai Y, Kambara T, Takeshima Y.
Front. Oncol. doi: 10.3389/fonc.2018.00446
MUC21 is a novel, negative immunohistochemical marker for epithelioid mesothelioma for its differentiation from lung adenocarcinoma.
Kai Y, Amatya VJ, Kushitani K, Kambara T, Suzuki R, Tsutani Y, Miyata Y, Okada M, Takeshima Y.
Histopathology. 2018 Oct 17. doi: 10.1111/his.13775.
Utility of Survivin, BAP1, and Ki‑67 immunohistochemistry in distinguishing epithelioid mesothelioma from reactive mesothelial hyperplasia.
Kushitani K, Amatya VJ, Mawas AS, Suzuki R, Miyata Y, Okada M, Inai K, Kishimoto T, Takeshima Y.
Oncol Lett. 2018 Mar;15(3):3540-3547.
Glypican-1 immunohistochemistry is a novel marker to differentiate epithelioid mesothelioma from lung adenocarcinoma.
Amatya VJ,Kushitani K, Kai Y, Suzuki R, Miyata Y, Okada M, Takeshima Y.
Mod Pathol. 2018 May;31(5):809-815.
MUC4 immunohistochemistry is useful in distinguishing epithelioid mesothelioma from adenocarcinoma and squamous cell carcinoma of the lung.
Mawas AS, Amatya VJ, Kushitani K, Kai Y, Miyata Y, Okada M, Takeshima Y.
Scientific Reports 8, Article number: 134 (2018) OPEN ACCESS
Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for its Differentiation From Pulmonary Adenocarcinoma.
Kuraoka M, Amatya VJ, Kushitani K, Mawas AS, Miyata Y, Okada M, Kishimoto T, Inai K, Nishisaka T, Sueda T, Takeshima Y.
Am J Surg Pathol. 2017 Aug;41(8):1045-1052.
PIM1 knockdown inhibits cell proliferation and invasion of mesothelioma cells.
Mawas AS, Amatya VJ, Suzuki Rui, Kushitani K, Mohi El-Din MM, Takeshima Y
Interntional Journal of Oncology; 2017 Mar; 50(3):1029-1034
MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma.
Amatya VJ, Mawas AS, Kushitani K, Miyata Y, Okada M, Kishimoto T, Inai K, Takeshima Y.
Modern Pathology, 2017 May; 30(5):672-681
Utility and pitfall of Immunohistochemistry in the Differential Diagnosis between Epithelioid Mesothelioma and Poorly Differentiated Lung Squamous Cell Carcinoma.
Kushitani K, Amatya VJ, Okada Y, Katayama Y, Mawas AS, Miyata Y, Okada M, Inai K, Kishimoto T, Takeshima Y.
Histopathology. 2017 Feb;70(3):375-384.
Pleural irregularities and mediastinal pleural involvement in early stages of malignant pleural mesothelioma and benign asbestos pleural effusion.
Kato K, Gemba K, Fujimoto N, Aoe K, Takeshima Y, Inai K, Kishimoto T.
Eur J Radiol. 2016 Sep;85(9):1594-600.
Fatal pleural mesothelioma in Japan (2003-2008): evaluation of computed tomography findings.
Kato K, Gemba K, Fujimoto N, Aoe K, Takeshima Y, Inai K, Kishimoto T.
Jpn J Radiol. 2016 Jun;34(6):432-8.
Computed Tomographic Features of Malignant Peritoneal Mesothelioma.
Kato K, Gemba K, Fujimoto N, Aoe K, Takeshima Y, Inai K, Kishimoto T.
Anticancer Res. 2016 Mar;36(3):1067-72.
Differential microRNA expression profiling of mesothelioma and expression analysis of miR-1 and miR-214 in mesothelioma.
Amatya VJ, Mawas AS, Kushitani K, Mohi El-Din MM, Takeshima Y.
Int J Oncol. 2016 Jan 26. doi: 10.3892/ijo.2016.3358. [Epub ahead of print]
Use of Anti-Noxa Antibody for Differential Diagnosis between Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia.
Kushitani K, Amatya VJ, Mawas AS, Miyata Y, Okada M, Takeshima Y.
Pathobiology. 2016;83(1):33-40.
CD9 expression as a favorable prognostic marker for patients with malignant mesothelioma
Amatya VJ, Takeshima Y, Aoe K, Fujimoto N, Okamoto T, Yamada T, Kishimoto T, Morimoto C, and Inai K.
Oncology Reports; 2013; 29(1): 21-28
Treatment and survival analyses of malignant mesothelioma in Japan.
Gemba K, Fujimoto N, Aoe K, Kato K, Takeshima Y, Inai K, Kishimoto T.
Acta Oncol. 2013 May;52(4):803-8.
CD26 overexpression is associated with prolonged survival and enhanced chemosensitivity in malignant pleural mesothelioma.
Aoe K, Amatya VJ, Fujimoto N, Ohnuma K, Hosono O, Hiraki A, Fujii M, Yamada T, Dang NH, Takeshima Y, Inai K, Kishimoto T, Morimoto C.
Clincal Cancer Research; 2012; 18(5): 1447-56
National survey of malignant mesothelioma and asbestos exposure in Japan.
Gemba K, Fujimoto N, Kato K, Aoe K, Takeshima Y, Inai K, Kishimoto T.
Cancer Sci. 2012 Mar;103(3):483-90.
Overexpression of CD26/DPPIV in Mesothelioma Tissue and Mesothelioma Cell Lines.
Amatya VJ, Takeshima Y, Kushitani K, Yamada T, Morimoto C, and Inai K.
Oncology Reports; 2011; 26(6): 1369-75
Aberrant promoter methylation of WIF-1 and SFRP1, 2, 4 genes in mesothelioma
Kohno H, Amatya VJ, Takeshima Y, Kushitani K, Hattori N, Kohno N, Inai K.
Oncology Report, 24(2) : 423-431, 2010
Evaluation of apoptosis and immunohistochemical expression of the apoptosis-related proteins in mesothelioma.
Jin L, Amatya VJ, Takeshima Y, Shrestha L, Kushitani K, Inai K.
Hiroshima Journal of Medical Sciences, 59(2) : 27-33, 2010.
Myogenic antigen expression is useful for differentiation between epithelioid mesothelioma and non-neoplastic mesothelial cells.
Tsukiji H, Takeshima Y, Amatya VJ, Kushitani K, Inai K
Histopathology, 56(7) : 969-974, 2010
Clinical study on mesothelioma in Japan: Relevance to occupational asbestos exposure.
Kishimoto T, Gemba K, Fujimoto N, Aoe K, Kato K, Takeshima Y, Inai K.
Am J Ind Med. 2010 Nov;53(11):1081-7.
Caveolin-1 is a novel immunohistochemical marker to differentiated epithelioid mesothelioma from lung adenocarcinoma.
Amatya VJ, Takeshima Y, Kohno H, Kushitani K, Yamada T, Morimoto C, Inai K.
Histopathology, 55(1) : 10-19, 2009.
Value of immunohistochemistry in the differential diagnosis of pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma.
Takeshima Y, Amatya VJ, Kushitani K, Kaneko M,Inai K.
Histopathology, 54(6) : 667-676, 2009.
Accuracy of pathological diagnosis of mesothelioma cases in Japan: Clinicopathological analysis 382 of cases.
Takeshima Y, Inai K, Amatya VJ, Gemba K, Aoe K, Fujimoto N, Kato K, Kishimoto T.
Lung Cancer, 66(2) : 191-197, 2009
A useful antibody panel for differential diagnosis between peritoneal mesothelioma and ovarian serous carcinoma in Japanese cases.
Takeshima Y, Amatya VJ, Kushitani K, Inai K.
American Journal of Clinical Pathology, 130(5) : 771-779, 2008
Differential diagnosis of sarcomatoid mesothelioma from true sarcoma and sarcomatoid carcinoma using immunohistochemistry.

Kushitani K, Takeshima Y, Amatya VJ, Furonaka O, Sakatani A, Inai K.
Pathology International, 58(2) : 75-83, 2008

Immunohistochemical marker panels for distinguishing between epithelioid mesothelioma and lung adenocarcinoma.
Kushitani K, Takeshima Y, Amatya VJ, Furonaka O, Sakatani A, Inai K.
Pathology International, 57(4) : 190-199, 2007

Other Research of our Department

Previous Researches of Lung Cancer

MUSTARD GAS & 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.

ATOMIC BOMB SURVIVOR & LUNG CANCER

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

Yuichoro Kai

4th Yr PhD Student
PhD Student

Yuichoro Kai

2nd Yr PhD Student
PhD Student

RUI SUZUKI

3rd Yr MD/PhD Student
PhD Student

YUTARO FUJII

1st Yr MD/PhD Student

Clinical Professors

Megumi Fujiwara

Department of Pathology,
Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

Takashi Nishisaka

Department of Pathology,
Hiroshima Prefectural Hospital, Hiroshima, Japan.

Mayumi Kaneko

Department of Pathology,
Hiroshima City Asa Hospital, Hiroshima, Japan.

Past Members

Masatsugu Kuraoka

Amany Sayed Mawas

Practice for Medical Research

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
Daijyo Shiota
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
     byouri2 @ hiroshima-u.ac.jp
2012
広島大学大学院 医系科学研究科
病理学研究室
2012
広島大学大学院 医系科学研究科 病理学研究室
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