Faculty Profiles - HIRASAWA Akira

Papers - HIRASAWA Akira

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Analysis of a correlation between the BRAF V600E mutation and abnormal DNA mismatch repair in patients with sporadic endometrial cancer

Makiko Kawaguchi, Megumi Yanokura, Kouji Banno, Yusuke Kobayashi, Yoshiko Kuwabara, Maya Kobayashi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Datsuke Aoki

INTERNATIONAL JOURNAL OF ONCOLOGY 34 ( 6 ) 1541 - 1547 2009.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Point mutations of KRAS and BRAF genes are thought to be important in carcinogenesis of colon cancer. In particular, gene instability caused by decreased expression of the hMLH1 gene, a DNA mismatch repair (MMR) gene, may be linked to the activating BRAF V600E point mutation in sporadic colon cancer. However, a consensus has not been established regarding the correlation between point mutations of KRAS or BRAF and carcinogenesis in patients with endometrial cancer, which is closely related to colon cancer. Therefore, we analyzed aberrant hypermethylation of the hMLH1 gene, microsatellite instability (MSI), and point mutations of KRAS and BRAF in 44 samples of sporadic endometrial cancer, with the aim of examining the mechanism of carcinogenesis in patients with endometrial cancer. Aberrant hMLH1 hypermethylation was found in 17 of the 44 cases (38.6%) and showed a significant positive correlation with MSI (p=0.02). This suggests that an abnormal MMR mechanism plays an important role in carcinogenesis of sporadic endometrial cancer. Point mutation of KRAS was found in 6 of the 44 cases (13.6%), but no BRAF V600E mutation was detected. These data suggest that the BRAF V600E mutation is not the target gene for abnormal MMR in carcinogenesis in patients with sporadic endometrial cancer, unlike in colon cancer. This is supported by the relatively few previous reports indicating a correlation between endometrial cancer and the BRAF V600E mutation. Identification of new candidates for the target gene for abnormal MMR in endometrial cancer requires further work.

DOI： 10.3892/ijo_00000283

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Endometrial cancer as HNPCC associated tumor

Kouji Banno, Yusuke Kobayashi, Megumi Yanokura, Arisa Kishimi, Seiji Ogawa, Iori Kisu, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

家族性腫瘍 9 ( 2 ) 64-68 2009.5

Endometrial Cancer as a Familial Tumor: Pathology and Molecular Carcinogenesis (Review) Reviewed

Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Makiko Kawaguchi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

CURRENT GENOMICS 10 ( 2 ) 127 - 132 2009.4

Language：English Publishing type：Research paper (scientific journal) Publisher：BENTHAM SCIENCE PUBL LTD

Some cases of endometrial cancer are associated with a familial tumor and are referred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Such tumors are thought to be induced by germline mutation of the DNA mismatch repair (MMR) gene, but many aspects of the pathology of familial endometrial cancer are unclear and no effective screening method has been established. However, the pathology of endometrial cancer with familial tumor has been progressively clarified in recent studies. At present, about 0.5% of all cases of endometrial cancers meet the clinical diagnostic criteria for HNPCC. A recent analysis of the three MMR genes (hMLH1, hMSH2 and hMSH6) revealed germline mutations in 18 of 120 cases (15.0%) of endometrial cancer with familial accumulation of cancer or double cancer, with a frameshift mutation of the hMSH6 gene being the most common. Many cases with mutation did not meet the current clinical diagnostic criteria for HNPCC, indicating that familial endometrial cancer is often not diagnosed as HNPCC. The results suggest that the hMSH6 gene mutation may be important in carcinogenesis in endometrial cancer and germline mutations of the MMR gene may be more prevalent in cases associated with familial accumulation of cancer. An international large-scale muticenter study is required to obtain further information about the pathology of endometrial cancer as a familial tumor.

DOI： 10.2174/138920209787847069

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結合型エストロゲン製剤を用いたホルモン補充療法の腰椎骨密度に対する長期的な効果の検討～当科更年期外来における継続投与10年例の結果から～

AOKI DAISUKE

Osteoporosis Japan 17 ( 2 ) 329-330 - 330 2009.4

Endometrial cancer as a familial tumor: pathology and molecular carcinogenesis (review). International journal

Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Makiko Kawaguchi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

Current genomics 10 ( 2 ) 127 - 32 2009.4

Language：English Publishing type：Research paper (scientific journal)

DOI： 10.2174/138920209787847069

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当科更年期外来における更年期不定愁訴に対する漢方薬の使用状況について-8年前の調査結果との比較検討-.

牧田和也, 堀場裕子, 平沢晃, 岩田卓, 片岡史夫, 冨永英一郎, 堀口文, 青木大輔, 吉村泰典

産婦人科漢方研究のあゆみ 26 ( 26 ) 44-47 - 47 2009

更年期外来受診患者における動脈硬化性疾患の危険因子に関する検討.

柳本茂久, 牧田和也, 堀場裕子, 平沢晃, 高松潔, 堀口文, 青木大輔

日本更年期医学会雑誌 17 ( 2 ) 171-178 - 178 2009

Endometrial cancer as a familial tumor: Pathology and molecular carcinogenesis (review)

Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Makiko Kawaguchi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

Current Genomics 10 ( 2 ) 127 - 132 2009

Language：English

DOI： 10.2174/138920209787847069

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閉経後骨粗鬆症に対する予防的治療を行う際の薬剤選択に関する再検証.

牧田和也, 平沢晃, 堀場裕子, 弟子丸亮太, 柳本茂久, 堀口文, 青木大輔

Osteoporosis Japan 17 ( 3 ) 447-449 - 449 2009

子宮体がん例におけるFRAXを用いた骨折リスク評価.

平沢晃, 牧田和也, 堀場裕子, 弟子丸亮太, 柳本茂久, 阪埜浩司, 進伸幸, 青木大輔

Osteoporosis Japan 17 ( 3 ) 492-495 - 495 2009

当科更年期外来における塩酸ラロキシフェン治療の現況-子宮体癌術後症例を中心に-.

牧田和也, 堀場裕子, 岩田卓, 平沢晃, 片岡史夫, 富永英一郎, 堀口文, 青木大輔

SERM 7 106-107 2009

Can ABCF2 protein expression predict the prognosis of uterine cancer? Reviewed

S. Nishimura, H. Tsuda, Y. Miyagi, A. Hirasawa, A. Suzuki, F. Kataoka, H. Nomura, T. Chiyoda, K. Banno, T. Fujii, N. Susumu, D. Aoki

BRITISH JOURNAL OF CANCER 99 ( 10 ) 1651 - 1655 2008.11

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Uterine cervical and endometrial cancers are common malignant solid neoplasms for which there are no useful prognostic markers. In this study, we evaluate the relationship between ATP-binding cassette superfamily F2 (ABCF2) expression and clinical factors including clinical stage, histologic type, grade and prognosis in uterine cervical and endometrial cancer. Two hundred and sixty seven cervical and 103 endometrial cancers were studied. ATP-binding cassette superfamily F2 cytoplasmic expression was detected by immunohistochemical staining and scored as positive or negative. Among cervical cancer cases, 149 (55.8%) expressed ABCF2. The overall survival was longer in ABCF2-negative than ABCF2-positive cases (P=0.0069). Statistically significant prognostic factors for survival were ABCF2 positivity ( risk ratio (rr) = 1.437), old age (rr = 1.550) and advanced stage (rr = 2.577). ATP-binding cassette superfamily F2 positivity was an independent prognostic factor by multivariate proportional hazard test (P=0.0002). Among endometrial cancer cases, 72 (69.9%) were cytoplasmic ABCF2 positive. However, there was no significant relationship between ABCF2 expression and age, clinical stage, histologic type, histologic grade, oestrogen receptor status or prognosis. ATP-binding cassette superfamily F2 expression may be a useful prognostic marker in cervical but not endometrial cancer. The role of ABCF2 protein may differ depending on the type of cancer.

DOI： 10.1038/sj.bjc.6604734

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Can ABCF2 protein expression predict the prognosis of uterine cancer?

S. Nishimura, H. Tsuda, Y. Miyagi, A. Hirasawa, A. Suzuki, F. Kataoka, H. Nomura, T. Chiyoda, K. Banno, T. Fujii, N. Susumu, D. Aoki

BRITISH JOURNAL OF CANCER 99 ( 10 ) 1651 - 1655 2008.11

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

DOI： 10.1038/sj.bjc.6604734

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子宮がん患者へのインフォームドコンセント（IC）

AOKI DAISUKE

臨床腫瘍プラクティス 4 ( 4 ) 313-319 - 319 2008.11

Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer. Reviewed International journal

Kokichi Sugano, Seigo Nakamura, Jiro Ando, Shin Takayama, Hiroyuki Kamata, Isao Sekiguchi, Megumi Ubukata, Tetsuro Kodama, Masami Arai, Fujio Kasumi, Yasuo Hirai, Tadashi Ikeda, Hiromitsu Jinno, Masaki Kitajima, Daisuke Aoki, Akira Hirasawa, Yuko Takeda, Kumiko Yazaki, Takashi Fukutomi, Takayuki Kinoshita, Ryuichiro Tsunematsu, Teruhiko Yoshida, Masako Izumi, Shino Umezawa, Hiroshi Yagata, Hiroko Komatsu, Naoko Arimori, Noriko Matoba, Nobuhisa Gondo, Shiro Yokoyama, Yoshio Miki

Cancer science 99 ( 10 ) 1967 - 76 2008.10

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

The prevalence of BRCA1/2 germline mutations in Japanese patients suspected to have hereditary breast/ovarian cancer was examined by a multi-institutional study, aiming at the clinical application of total sequencing analysis and validation of assay sensitivity in Japanese people using a cross-sectional approach based on genetic factors estimated from personal and family histories. One hundred and thirty-five subjects were referred to the genetic counseling clinics and enrolled in the study. Full sequencing analysis of the BRCA1/2 gene showed 28 types of deleterious mutations in 36 subjects (26.7%), including 13 types of BRCA1 mutations in 17 subjects (12.6%) and 15 types of BRCA2 mutations in 19 subjects (14.1%). Subjects were classified into five groups and 22 subgroups according to their personal and family history of breast and/or ovarian cancer, and the prevalence of deleterious mutations was compared with previously reported data in non-Ashkenazi individuals. Statistical analysis using the Mantel-Haenszel test for groups I through IV revealed that the prevalence of Japanese subjects was significantly higher than that of non-Ashkenazi individuals (P = 0.005, odds ratio 1.87, 95% confidence interval 1.22-2.88). Family history of the probands suffering from breast cancer indicated risk factors for the presence of deleterious mutations of BRCA1/2 as follows: (1) families with breast cancer before age 40 within second degree relatives (P = 0.0265, odds ratio 2.833, 95% confidence interval 1.165-7.136) and (2) families with bilateral breast cancer and/or ovarian cancer within second degree relatives (P = 0.0151, odds ratio 2.88, 95% confidence interval 1.25-6.64).

DOI： 10.1111/j.1349-7006.2008.00944.x

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Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer

CANCER SCIENCE 99 ( 10 ) 1967 - 1976 2008.10

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

DOI： 10.1111/j.1349-7006.2008.00944.x

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子宮体がん術後患者における骨密度の特徴に関する検討.

平沢晃, 牧田和也, 堀場裕子, 弟子丸亮太, 柳本茂久, 野村弘行, 片岡史夫, 岩田卓, 冨永英一郎, 阪埜浩司, 進伸幸, 堀口文, 青木大輔