研究者詳細 - 平沢　晃

論文 - 平沢　晃

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ADAM9 is over-expressed in human ovarian clear cell carcinomas and suppresses cisplatin-induced cell death 査読国際誌

Mari Ueno, Takayuki Shiomi, Satsuki Mochizuki, Miyuki Chijiiwa, Masayuki Shimoda, Yae Kanai, Fumio Kataoka, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki, Yasunori Okada

CANCER SCIENCE 109 ( 2 ) 471 - 482 2018年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

ADAMs (a disintegrin and metalloproteinases) are involved in various biological events such as cell adhesion, migration and invasion, membrane protein shedding and proteolysis. However, there have been no systematic studies on the expression of ADAMs in human ovarian carcinomas. We therefore examined mRNA expression of all the proteolytic ADAM species including ADAM8, 9, 10, 12, 15, 17, 19, 20, 21, 28, 30, 33 and ADAMDEC1 in human ovarian carcinomas, and found that prototype membrane-anchored ADAM9m, but not secreted isoform ADAM9s, is significantly over-expressed in carcinomas than in control non-neoplastic ovarian tissue. Among the histological subtypes of serous, endometrioid, mucinous and clear cell carcinomas, ADAM9m expression was highest in clear cell carcinomas. Immunohistochemistry showed that all the clear cell carcinoma samples displayed ADAM9m primarily on the carcinoma cell membrane. By immunoblotting, ADAM9m was detected mainly in an active form in the clear cell carcinoma tissues. When two clear cell carcinoma cell lines (RMG-I and TOV21G cells) with ADAM9m expression were treated with cisplatin, viability was significantly reduced and apoptosis increased in ADAM9m knockdown cells compared with mock transfectants. In addition, treatment of the cells with neutralizing anti-ADAM9m antibody significantly decreased viability compared with non-immune IgG, whereas ADAM9m over-expression significantly increased viability compared with mock transfectants. Our data show, to the best of our knowledge, for the first time, that ADAM9m is over-expressed in an activated form in human ovarian clear cell carcinomas, and suggest that ADAM9m plays a key role in cisplatin resistance.

DOI： 10.1111/cas.13469

Japanese Society for Cancer of the Colon and Rectum (JSCCR) Guidelines 2016 for the Clinical Practice of Hereditary Colorectal Cancer (Translated Version). 査読

Hideyuki Ishida, Tatsuro Yamaguchi, Kohji Tanakaya, Kiwamu Akagi, Yasuhiro Inoue, Kensuke Kumamoto, Hideki Shimodaira, Shigeki Sekine, Toshiaki Tanaka, Akiko Chino, Naohiro Tomita, Takeshi Nakajima, Hirotoshi Hasegawa, Takao Hinoi, Akira Hirasawa, Yasuyuki Miyakura, Yoshie Murakami, Kei Muro, Yoichi Ajioka, Yojiro Hashiguchi, Yoshinori Ito, Yutaka Saito, Tetsuya Hamaguchi, Megumi Ishiguro, Soichiro Ishihara, Yukihide Kanemitsu, Hiroshi Kawano, Yusuke Kinugasa, Norihiro Kokudo, Keiko Murofushi, Takako Nakajima, Shiro Oka, Yoshiharu Sakai, Akihiko Tsuji, Keisuke Uehara, Hideki Ueno, Kentaro Yamazaki, Masahiro Yoshida, Takayuki Yoshino, Narikazu Boku, Takahiro Fujimori, Michio Itabashi, Nobuo Koinuma, Takayuki Morita, Genichi Nishimura, Yuh Sakata, Yasuhiro Shimada, Keiichi Takahashi, Shinji Tanaka, Osamu Tsuruta, Toshiharu Yamaguchi, Kenichi Sugihara, Toshiaki Watanabe

Journal of the anus, rectum and colon 2 ( Suppl I ) S1-S51 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）

Hereditary colorectal cancer accounts for less than 5% of all colorectal cancer cases. Some of the unique characteristics that are commonly encountered in cases of hereditary colorectal cancer include early age at onset, synchronous/metachronous occurrence of the cancer, and association with multiple cancers in other organs, necessitating different management from sporadic colorectal cancer. While the diagnosis of familial adenomatous polyposis might be easy because usually 100 or more adenomas that develop in the colonic mucosa are in this condition, Lynch syndrome, which is the most commonly associated disease with hereditary colorectal cancer, is often missed in daily medical practice because of its relatively poorly defined clinical characteristics. In addition, the disease concept and diagnostic criteria for Lynch syndrome, which was once called hereditary non-polyposis colorectal cancer, have changed over time with continual research, thereby possibly creating confusion in clinical practice. Under these circumstances, the JSCCR Guideline Committee has developed the "JSCCR Guidelines 2016 for the Clinical Practice of Hereditary Colorectal Cancer (HCRC)," to allow delivery of appropriate medical care in daily practice to patients with familial adenomatous polyposis, Lynch syndrome, or other related diseases. The JSCCR Guidelines 2016 for HCRC were prepared by consensus reached among members of the JSCCR Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR Guidelines 2016 for HCRC.

DOI： 10.23922/jarc.2017-028

Genetic Testing and Clinical Management Practices for Variants in Non-BRCA1/2 Breast (and Breast/Ovarian) Cancer Susceptibility Genes: An International Survey by the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Clinical Working Group. 査読国際誌

Sarah M Nielsen, Diana M Eccles, Iris L Romero, Fahd Al-Mulla, Judith Balmaña, Michela Biancolella, Rien Bslok, Maria Adelaide Caligo, Mariarosaria Calvello, Gabriele Lorenzo Capone, Pietro Cavalli, T L Chris Chan, Kathleen B M Claes, Laura Cortesi, Fergus J Couch, Miguel de la Hoya, Simona De Toffol, Orland Diez, Susan M Domchek, Ros Eeles, Anna Efremidis, Florentia Fostira, David Goldgar, Andreas Hadjisavvas, Thomas V O Hansen, Akira Hirasawa, Claude Houdayer, Petra Kleiblova, Sophie Krieger, Conxi Lázaro, Maria Loizidou, Siranoush Manoukian, Arjen R Mensenkamp, Setareh Moghadasi, Alvaro N Monteiro, Luigi Mori, April Morrow, Nadia Naldi, Henriette R Nielsen, Olufunmilayo I Olopade, Nicholas S Pachter, Edenir I Palmero, Inge S Pedersen, Maria Piane, Marianna Puzzo, Mark Robson, Maria Rossing, Maria Christina Sini, Angela Solano, Jana Soukupova, Gianluca Tedaldi, Manuel Teixeira, Mads Thomassen, Maria Grazia Tibiletti, Amanda Toland, Therese Törngren, Erica Vaccari, Liliana Varesco, Ana Vega, Yvonne Wallis, Barbara Wappenschmidt, Jeffrey Weitzel, Amanda B Spurdle, Arcangela De Nicolo, Encarna B Gómez-García

JCO precision oncology 2 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）

Purpose: To describe a snapshot of international genetic testing practices, specifically regarding the use of multigene panels, for hereditary breast/ovarian cancers. We conducted a survey through the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium, covering questions about 16 non-BRCA1/2 genes. Methods: Data were collected via in-person and paper/electronic surveys. ENIGMA members from around the world were invited to participate. Additional information was collected via country networks in the United Kingdom and in Italy. Results: Responses from 61 cancer genetics practices across 20 countries showed that 16 genes were tested by > 50% of the centers, but only six (PALB2, TP53, PTEN, CHEK2, ATM, and BRIP1) were tested regularly. US centers tested the genes most often, whereas United Kingdom and Italian centers with no direct ENIGMA affiliation at the time of the survey were the least likely to regularly test them. Most centers tested the 16 genes through multigene panels; some centers tested TP53, PTEN, and other cancer syndrome-associated genes individually. Most centers reported (likely) pathogenic variants to patients and would test family members for such variants. Gene-specific guidelines for breast and ovarian cancer risk management were limited and differed among countries, especially with regard to starting age and type of imaging and risk-reducing surgery recommendations. Conclusion: Currently, a small number of genes beyond BRCA1/2 are routinely analyzed worldwide, and management guidelines are limited and largely based on expert opinion. To attain clinical implementation of multigene panel testing through evidence-based management practices, it is paramount that clinicians (and patients) participate in international initiatives that share panel testing data, interpret sequence variants, and collect prospective data to underpin risk estimates and evaluate the outcome of risk intervention strategies.

DOI： 10.1200/PO.18.00091

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer. 招待査読国際誌

Akira Hirasawa, Issei Imoto, Takuya Naruto, Tomoko Akahane, Wataru Yamagami, Hiroyuki Nomura, Kiyoshi Masuda, Nobuyuki Susumu, Hitoshi Tsuda, Daisuke Aoki

Oncotarget 8 ( 68 ) 112258 - 112267 2017年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：(in press)

Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

DOI： 10.18632/oncotarget.22733

Efficacy and safety of dose-dense paclitaxel plus carboplatin as neoadjuvant chemotherapy for advanced ovarian, fallopian tube or peritoneal cancer 査読国際誌

Tomoko Yoshihama, Hiroyuki Nomura, Naomi Iwasa, Fumio Kataoka, Shiho Hashimoto, Yoshiko Nanki, Takuro Hirano, Takeshi Makabe, Kensuke Sakai, Wataru Yamagami, Akira Hirasawa, Daisuke Aoki

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 47 ( 11 ) 1019 - 1023 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

Interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) is currently one of the preferred treatment options for advanced ovarian, fallopian tube or peritoneal cancer. This study was conducted to evaluate the clinical efficacy and safety of dose-dense paclitaxel plus carboplatin therapy (ddTC therapy) as NAC for these cancers.A retrospective study was conducted in 25 patients with Stage III/IV ovarian, fallopian tube or peritoneal cancer who received ddTC therapy as NAC. For ddTC therapy, paclitaxel (80 mg/m(2)) was administered intravenously on Days 1, 8 and 15 and carboplatin (AUC 6.0 mg/ml x min) was administered intravenously on Day 1 every 3 weeks. IDS was performed after three cycles of ddTC therapy, and ddTC therapy was also continued after surgery.With ddTC therapy as NAC, the response rate was 92% and disease progression did not occur in any patient. Grade 4 hematologic toxicity and >= Grade 3 non-hematologic toxicity both occurred in 8% of the patients, but no patient discontinued NAC because of adverse events. When IDS was performed, the complete surgery rate was 64% and the optimal surgery rate was 96%. >= Grade 3 perioperative complications occurred in 16% of the patients, but there were no perioperative deaths. Median overall survival was 35.7 months and median progression-free survival was 17.7 months.This study showed that ddTC therapy was considerably effective and tolerable as NAC. The complete surgery rate was high with IDS, and perioperative complications were acceptable.

DOI： 10.1093/jjco/hyx118

治療薬解説 PARP阻害薬

平沢晃, 青木大輔

カレントテラピー 35 ( 9 ) 74 - 77 2017年9月

A Comparison of Dye Versus Fluorescence Methods for Sentinel Lymph Node Mapping in Endometrial Cancer 査読国際誌

Wataru Yamagami, Nobuyuki Susumu, Fumio Kataoka, Takeshi Makabe, Kensuke Sakai, Tomomi Ninomiya, Michiko Wada, Hiroyuki Nomura, Akira Hirasawa, Kouji Banno, Tadaki Nakahara, Kaori Kameyama, Daisuke Aoki

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 27 ( 7 ) 1517 - 1524 2017年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Objective Sentinel nodes (SNs) have been observed in several reports from Japan and overseas in cases with endometrial cancer; however, no consensus has been reached regarding the types of tracers or the method of their injection. A combination of the radioisotope (RI) and dye method is considered to be desirable. We assessed SN mapping using either dye or near-infrared fluorescence imaging to clarify a suitable method in cases of endometrial cancer.Methods Patients were enrolled from 92 patients diagnosed with endometrial cancer and having no extrauterine metastasis by the preoperative imaging between 2009 and 2014 at our institution. To identify the SNs, we performed 3 methods using either dye or fluorescence solutions in conjunction with a RI method. In the dye method, we injected indocyanine green in the uterine subserosa, visually identifying SNs as stained green. In the fluorescence method, a dilute indocyanine green solution (0.5 mg, fluorescence A or 0.25 mg, fluorescence B, each per 10 mL of solvent) was injected and the SN identified by the HyperEye Medical System.Results The SN detection rates were 100%, 100%, and 96% using dye and fluorescence A or B solution, respectively. Pelvic SNs were detected by the 3 methods in 98%, 100%, and 96% of cases and para-aortic SNs in 65%, 88%, and 74%, respectively. Fluorescence A solution was somewhat better than dye in detecting para-aortic SNs, although not significantly so (P = 0.07). The sensitivity and negative predictive values for detecting SNs with metastases with the dye method were 92% and 98% compared with 100% and 100%, respectively, for both fluorescence solutions.Conclusions Although both dye and fluorescence methods performed well, no method perfectly identified para-aortic SNs. The concomitant use of the RI method is required to detect para-aortic SNs.

DOI： 10.1097/IGC.0000000000000997

遺伝性卵巣がん

千代田達幸, 平沢晃, 青木大輔

成人病と生活習慣病 47 ( 7 ) 861 - 866 2017年7月

記述言語：日本語出版者・発行元：(株)東京医学社

がんは遺伝因子と環境因子の双方が関与して発症するが、卵巣癌の約10〜15%は遺伝性乳癌卵巣癌症候群(hereditary breast and ovarian cancer;HBOC)の原因遺伝子であるBRCA1もしくはBRCA2(BRCA1/2)の生殖細胞系列変異に基づく。BRCA1/2変異保持者は卵巣癌のリスクが高く、がん予防策を講じる必要がある。もっとも確実なリスク低減策はリスク低減卵管卵巣摘出術(risk-reducing salpingo-oophorectomy;RRSO)であり、発癌リスクを80%減らすことができる。BRCA1/2変異のある癌に対しては合成致死作用によりPARP阻害薬が奏効する。PARP阻害薬のコンパニオン診断としてBRCA1/2遺伝子検査が行われるようになり、precision medicineの先駆けとしてゲノム医療の実用化が始まっている。(著者抄録)

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J03723&link_issn=&doc_id=20170807200010&doc_link_id=%2Faq9seijd%2F2017%2F004707%2F010%2F0861-0866%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9seijd%2F2017%2F004707%2F010%2F0861-0866%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

医療機器に生じたトラブル

冨永英一郎, 小林佑介, 平沢晃, 阪埜浩司, 末岡浩, 青木大輔

産婦人科の実際 66 ( 6 ) 767 - 771 2017年6月

Clinical utility of a self-administered questionnaire for assessment of hereditary gynecologic cancer. 国際誌

Kenta Masuda, Akira Hirasawa, Haruko Irie-Kunitomi, Tomoko Akahane, Arisa Ueki, Yusuke Kobayashi, Wataru Yamagami, Hiroyuki Nomura, Fumio Kataoka, Eiichiro Tominaga, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

Japanese journal of clinical oncology 47 ( 5 ) 401 - 406 2017年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: A patient's medical history and familial cancer history are important information for assessing the risk of hereditary cancer. We have generated a self-administered questionnaire for patients with gynecologic cancer. This pilot study analyzed the usefulness of this questionnaire and the rates of patients that meet the Society of Gynecologic Oncology criteria in ovarian cancer and endometrial cancer patients. Method: Ovarian or endometrial cancer patients were recruited for this study. After informed consent was obtained, participants completed the questionnaire. Genetic risks were assessed from the data of each patient's questionnaire by Society of Gynecologic Oncology guideline. Clinical and pathological findings were compared between the genetic risk groups. Results: A total of 105 patients were identified with ovarian cancer and 56 patients with endometrial cancer eligible for this study. According to the Society of Gynecologic Oncology guideline, of the 105 ovarian cancer patients, 25 patients (23%) had a 20-25% risk and three patients (2.9%) had a 5-10% risk of hereditary breast and ovarian cancer syndrome. A further 22 patients (21%) had a 5-10% risk of Lynch syndrome. Two patients (1.9%) met the Amsterdam criteria II. Of 56 endometrial cancer patients, 24 patients (42.9%) had a 5-10% risk of Lynch syndrome. The endometrial cancer patients with genetic risk of Lynch syndrome were younger (mean age: 47.79) at diagnosis compared to patients without a genetic risk of Lynch syndrome (mean age: 57.91). Conclusions: In this study, we were able to show that the newly designed questionnaire is a useful tool for evaluating cancer family history along with Society of Gynecologic Oncology criteria or Amsterdam criteria II. When considering the risk of Lynch syndrome for a patient with ovarian cancer, it is important to collect a second and third relative's family history.

DOI： 10.1093/jjco/hyx019

Clinical utility of a self-administered questionnaire for assessment of hereditary gynecologic cancer. 査読国際誌

Kenta Masuda, Akira Hirasawa, Haruko Irie-Kunitomi, Tomoko Akahane, Arisa Ueki, Yusuke Kobayashi, Wataru Yamagami, Hiroyuki Nomura, Fumio Kataoka, Eiichiro Tominaga, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

Japanese journal of clinical oncology 47 ( 5 ) 473 - 473 2017年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

This study shows that the newly designed self-administered questionnaire is a useful tool to assess the risk of hereditary cancer for patients with gynecologic cancer.A patient's medical history and familial cancer history are important information for assessing the risk of hereditary cancer. We have generated a self-administered questionnaire for patients with gynecologic cancer. This pilot study analyzed the usefulness of this questionnaire and the rates of patients that meet the Society of Gynecologic Oncology criteria in ovarian cancer and endometrial cancer patients.
Ovarian or endometrial cancer patients were recruited for this study. After informed consent was obtained, participants completed the questionnaire. Genetic risks were assessed from the data of each patient's questionnaire by Society of Gynecologic Oncology guideline. Clinical and pathological findings were compared between the genetic risk groups.
A total of 105 patients were identified with ovarian cancer and 56 patients with endometrial cancer eligible for this study. According to the Society of Gynecologic Oncology guideline, of the 105 ovarian cancer patients, 25 patients (23%) had a 20-25% risk and three patients (2.9%) had a 5-10% risk of hereditary breast and ovarian cancer syndrome. A further 22 patients (21%) had a 5-10% risk of Lynch syndrome. Two patients (1.9%) met the Amsterdam criteria II. Of 56 endometrial cancer patients, 24 patients (42.9%) had a 5-10% risk of Lynch syndrome. The endometrial cancer patients with genetic risk of Lynch syndrome were younger (mean age: 47.79) at diagnosis compared to patients without a genetic risk of Lynch syndrome (mean age: 57.91).
In this study, we were able to show that the newly designed questionnaire is a useful tool for evaluating cancer family history along with Society of Gynecologic Oncology criteria or Amsterdam criteria II. When considering the risk of Lynch syndrome for a patient with ovarian cancer, it is important to collect a second and third relative's family history.

DOI： 10.1093/jjco/hyx037

Carcinoma of the lower uterine segment diagnosed with Lynch syndrome based on MSH6 germline mutation: A case report. 査読国際誌

Masataka Adachi, Kouji Banno, Kenta Masuda, Megumi Yanokura, Moito Iijima, Takashi Takeda, Haruko Kunitomi, Yusuke Kobayashi, Wataru Yamagami, Akira Hirasawa, Kaori Kameyama, Kokichi Sugano, Daisuke Aoki

The journal of obstetrics and gynaecology research 43 ( 2 ) 416 - 420 2017年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Endometrial cancer in the lower uterine segment (LUS) is associated with Lynch syndrome with MLH1 or MSH2 germline mutation. Here, we report a case of carcinoma of the LUS diagnosed with Lynch syndrome based on MSH6 germline mutation in a 46-year-old woman with abnormal vaginal bleeding. She had had rectal cancer at age 39 with a family history of colon cancer (father, 75 years), pancreatic cancer (paternal grandmother, 74 years), and colon cancer (maternal grandmother, 85 years). Magnetic resonance imaging showed a tumor in the LUS. Endometrial biopsy revealed endometrioid adenocarcinoma G1. As her cancer history met the revised Bethesda criteria, we examined microsatellite instability and the result was negative, but loss of the MSH6 expression was detected by immunohistochemistry. Genetic testing revealed deleterious germline mutation of MSH6, which was compatible with Lynch syndrome. To our knowledge, this is the first case of endometrial carcinoma of the LUS with MSH6 germline mutation.

DOI： 10.1111/jog.13202

Carcinoma of the lower uterine segment diagnosed with Lynch syndrome based on MSH6 germline mutation: A case report 査読

Masataka Adachi, Kouji Banno, Kenta Masuda, Megumi Yanokura, Moito Iijima, Takashi Takeda, Haruko Kunitomi, Yusuke Kobayashi, Wataru Yamagami, Akira Hirasawa, Kaori Kameyama, Kokichi Sugano, Daisuke Aoki

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 43 ( 2 ) 416 - 420 2017年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Endometrial cancer in the lower uterine segment (LUS) is associated with Lynch syndrome with MLH1 or MSH2 germline mutation. Here, we report a case of carcinoma of the LUS diagnosed with Lynch syndrome based on MSH6 germline mutation in a 46-year-old woman with abnormal vaginal bleeding. She had had rectal cancer at age 39 with a family history of colon cancer (father, 75 years), pancreatic cancer (paternal grandmother, 74 years), and colon cancer (maternal grandmother, 85 years). Magnetic resonance imaging showed a tumor in the LUS. Endometrial biopsy revealed endometrioid adenocarcinoma G1. As her cancer history met the revised Bethesda criteria, we examined microsatellite instability and the result was negative, but loss of the MSH6 expression was detected by immunohistochemistry. Genetic testing revealed deleterious germline mutation of MSH6, which was compatible with Lynch syndrome. To our knowledge, this is the first case of endometrial carcinoma of the LUS with MSH6 germline mutation.

DOI： 10.1111/jog.13202

UGT1A1 polymorphism as a prognostic indicator of stage I ovarian clear cell carcinoma patients treated with irinotecan 査読国際誌

Tomoko Yoshihama, Akira Hirasawa, Hiroyuki Nomura, Tomoko Akahane, Yoshiko Nanki, Wataru Yamagami, Fumio Kataoka, Eiichiro Tominaga, Nobuyuki Susumu, Taisei Mushiroda, Daisuke Aoki

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 47 ( 2 ) 170 - 174 2017年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

We investigated whether UGT1A1 polymorphisms are associated with the prognosis of ovarian cancer patients treated with irinotecan. UGT1A1 genotypes were analyzed in 11 stage I ovarian clear cell carcinoma patients who received irinotecan as first-line therapy. Progression-free survival, overall survival and adverse events were also assessed for each genotype. Three patients harbored UGT1A1*1/*6 while another three harbored UGT1A1*1/*28. Two patients with a wildtype genotype experienced recurrence and one died, whereas no recurrence or death was observed in patients with heterozygous genotypes. Adverse events tended to be more severe in patients with UGT1A1*6 and *28, although progression-free survival and overall survival rates tended to be better than in wild-type; the differences were not significant. We conclude that UGT1A1 polymorphisms have the potential to be a prognostic marker of irinotecan treatment.

DOI： 10.1093/jjco/hyw163

遺伝性乳癌卵巣癌症候群と女性ヘルスケア招待

平沢晃, 青木大輔

更年期と加齢のヘルスケア 16 ( 1 ) 42 - 45 2017年

記述言語：日本語出版者・発行元：更年期と加齢のヘルスケア学会((NPO)更年期と加齢のヘルスケア)

遺伝性乳癌卵巣癌症候群(hereditary breast and ovarian cancer syndrome:HBOC)はBRCA1またはBRCA2遺伝子(BRCA1/2)の生殖細胞系列変異によるもので、BRCA1遺伝子変異保持者女性の卵巣癌発症リスクは39〜46%、BRCA2遺伝子変異保持者女性では12〜27%であると報告されている。HBOCは常染色体優性遺伝性疾患であり、血縁者にその関連疾患が多発することから、家族歴の聴取が発見の端緒となる。BRCA1/2変異保持者に対しては、がん発症リスクを理解した上で適切な対策を講じる必要がある。腫瘍遺伝学の臨床におけるエンドポイントは「遺伝子変異保持者におけるがん死の低減」である。その目的のため遺伝子変異保持者に対してはがん予防策をとることが必要となる。がん一次予防法としてはリスク低減卵管卵巣摘出術(risk-reducing salpingo-oophorectomy:RRSO)、リスク低減乳房切除術(risk-reducing mastectomy:RRM)、経口避妊薬による卵巣癌予防およびタモキシフェンによる乳癌予防などが挙げられる。そのなかでもRRSOは卵巣癌発症のリスク低減効果のみならず、乳癌発症リスク、さらには卵巣癌や乳癌による死亡率のみならず全死亡も低減すると報告されており、現時点でBRCA1/2遺伝子変異保持者に対する最も効果が高いがん一次予防法である。BRCA1/2遺伝子変異保持者に対するRRSOは本邦の実臨床に導入されてきている。しかしながらRRSOは閉経前に施行されることが多く、術後短期的には卵巣欠落症状、長期的には脂質異常症や骨粗鬆症などを発症してQOL低下をもたらす可能性が高い。海外の各種ガイドラインでは術後卵巣欠落症状に対するホルモン補充療法(ET療法)が提唱されているものの、乳癌既往例などET療法が困難な例が存在し、そのような場合は漢方療法が有効な場合がある。RRSO施行後は乳癌や腹膜癌などの発生についての「がんサーベイランス」とともに、女性ヘルスケアの観点からも経時的に追跡することが重要である。(著者抄録)

手術前禁忌薬（経口避妊薬,低用量エストロゲン-プロゲスチン配合薬）に関する医療安全対策査読

高柳裕子, 冨永英一郎, 小林佑介, 仲村勝, 片岡史夫, 平沢晃, 阪埜浩司, 田中守, 青木大輔

東京産科婦人科学会会誌 66 ( 3 ) 424 - 428 2017年

記述言語：日本語出版者・発行元：(一社)東京産科婦人科学会

当科において手術前禁忌薬である経口女性ホルモン製剤(OC・LEP)を内服している患者に、術前休薬の指示がされなかったために発生したインシデント事例について、後方視的に検討した。2015年1月から12月に、当院で入院のうえ手術を施行した1,250例のうち、OC・LEPを内服していた症例は17例であり、そのうち3例は術前に内服中止の指示がされず、手術延期となった。院内における対策として医療者への教育強化、医師への注意喚起、看護師・薬剤師によるダブルチェックなどのチェック機構強化を図った。その結果、当科においては手術前禁忌薬に関する同様のインシデント発生を防ぐことが可能となった。防御システムを多重化すること、医療者の認識を高めることが、インシデント発生を防止するために重要であると考えられた。(著者抄録)

一般病院における家族性腫瘍相談外来とハイリスク外来の開設 –一般病院み求められる家族性腫瘍診療の意義についての考察- . 招待査読

植木有紗, 中田さくら, 安斎純子, 麻薙美香, 嶋田恭輔, 久保内光一, 三須久美子, 平沢晃, 阪埜浩司, 菅野康吉, 小崎健次郎, 青木大輔

家族性腫瘍 16 ( 2 ) 38 - 43 2017年

記述言語：日本語出版者・発行元：(一社)日本遺伝性腫瘍学会

本邦における家族性腫瘍の遺伝カウンセリング体制は近年急速に整備されつつあるが,その多くは大学病院やセンター病院といった大規模病院である.今回我々は,地域がん診療連携拠点病院における家族性腫瘍相談外来開設の経験をもとに,一般市中病院での遺伝カウンセリング体制の課題などについて当院での現状を紹介し,考察する.依頼元の内訳は乳腺外科からの受診相談が約30%にのぼり,さらに遺伝学的検査の内訳で見ると43%が乳癌の術前依頼であり,受診動機として癌罹患者の術式選択が大きな要因になっていることが示唆された.また,受診された遺伝子変異保持者および血縁者を対象にハイリスク外来を同時に開設し,心理的支援とサーベイランスを継続している.今後もクライエントのために,一般市中病院の立場で家族性腫瘍に関する正しい情報提供およびサーベイランスや,診断後の治療を含む実地診療との密な協力体制の構築を目標に,よりクライエント中心型のカウンセリング体制の整備が必要と考える.(著者抄録)

DOI： 10.18976/jsft.16.2_38

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J03931&link_issn=&doc_id=20170714280003&doc_link_id=%2Fcg3kazok%2F2016%2F001602%2F003%2F0038-0043%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcg3kazok%2F2016%2F001602%2F003%2F0038-0043%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

BRCA1またはBRCA2遺伝子変異陽性女性へのHRT 招待

平沢晃, 高松潔, 青木大輔

産科と婦人科 84 ( 12 ) 1468 - 1471 2017年

記述言語：日本語出版者・発行元：(株)診断と治療社

近年、遺伝性乳癌卵巣癌症候群の原因遺伝子であるBRCA1またはBRCA2(BRCA1/2)遺伝子の遺伝学的検査が実地臨床に導入されてきている。今後はがん治療や予防の領域においてはBRCA1/2遺伝子のステータスに応じて、PARP(poly ADP ribose polymerase)阻害薬を用いた個別化治療法や、リスク低減卵管卵巣摘出術(risk-reducing salpingo-oophorectomy:RRSO)などの個別化予防法が実用化されることは確実である。そこで、BRCA1/2遺伝子変異保持者女性に対するHRTは女性医学、臨床腫瘍学、臨床遺伝学知見に基づいた統合的対応が必要である。(著者抄録)

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00525&link_issn=&doc_id=20171124130011&doc_link_id=%2Fae4sanke%2F2017%2F008412%2F012%2F1468-1471%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4sanke%2F2017%2F008412%2F012%2F1468-1471%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Consistency in drug response profiling. 査読国際誌

John Patrick Mpindi, Bhagwan Yadav, Päivi Östling, Prson Gautam, Disha Malani, Astrid Murumägi, Akira Hirasawa, Sara Kangaspeska, Krister Wennerberg, Olli Kallioniemi, Tero Aittokallio

Nature 540 ( 7631 ) E5-E6 - E6 2016年11月

Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis. 査読国際誌

Takashi Takeda, Kouji Banno, Megumi Yanokura, Masataka Adachi, Moito Iijima, Haruko Kunitomi, Kanako Nakamura, Miho Iida, Yuya Nogami, Kiyoko Umene, Kenta Masuda, Yusuke Kobayashi, Wataru Yamagami, Akira Hirasawa, Eiichiro Tominaga, Nobuyuki Susumu, Daisuke Aoki

Genes 7 ( 10 ) e86 2016年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1, MSH2, and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP). Germline mutation of MMR genes, microsatellite instability (MSI), and immunohistochemistry (IHC) were also analyzed in each case with epimutation. MLH1 epimutation was detected in a single patient out of a total of 206 (0.49%)-1 out of 58 (1.72%) with an onset age of less than 50 years. The patient with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6. The MLH1 epimutation detected in a patient with endometrial cancer may be a cause of endometrial carcinogenesis. This result indicates that it is important to check epimutation in patients with endometrial cancer without a germline mutation of MMR genes.

DOI： 10.3390/genes7100086

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