Details of a Researcher - Iwata, Takashi

Papers - Iwata, Takashi

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Dominant human papillomavirus 16 infection in cervical neoplasia in young Japanese women; study of 881 outpatients

Masumoto, N., Fujii, T., Ishikawa, M., Mukai, M., Ono, A., Iwata, T., Kubushiro, K. and Nozawa, S.

Gynecol Oncol 94 ( 2 ) 509 - 14 2004.08

ISSN 0090-8258

Human papillomavirus (HPV) infection is reported to be related to carcinogenesis in the uterine cervix. In Japan, screening for cervical cancer by cytology is performed in women over 30 years old. The purpose of this study was to determine whether there is an association between patient age and cervical neoplasia or HPV infection in Japanese women.|Specimens from 881 randomly selected patients who came to our clinic were tested for HPV DNA by using Hybrid Capture II, whereas specimens from a 204-patient randomly selected subset diagnosed with cervical neoplasia were tested for HPV DNA by using polymerase chain reaction (PCR). HPV typing was performed in all the PCR-positive cases.|The HPV-positive rate in the 20- to 29-year-old patients (29.0% in the normal cytology/histology group and 85.5% in the abnormal group) was higher than in the 30- to 59-year-old patients, and the rate declined until age 60 when age increased. While HPV 18, HPV 52, other HPV types, and HPV types as a whole were frequently detected in 30- to 49-year-old patients, HPV 16 was detected more frequently in the younger group than the other HPV types (P = 0.03). Among the HPV 16-positive patients with cervical neoplasia, the proportion of cervical intraepithelial neoplasia (CIN) 3 cases was high (44%) in the 20- to 29-year-old group.|Screening for cervical neoplasia by cytology should also be performed in women under 30 years old in Japan. The HPV typing could be a tool to strictly follow-up younger women who were diagnosed with CIN.

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Association of HNPCC and endometrial cancers

Banno Kouji, Susumu Nobuyuld, Yanokura Megumi, Hirao Takeshi, Iwata Takashi, Hirasawa Akira, Aoki Daisuke, Sugano Kokichi, Nozawa Shiro

International Journal of Clinical Oncology 9 ( 4 ) 262 - 269 2004.08

ISSN 1341-9625

Hereditary nonpolyposis colorectal cancer (HNPCC) is among the representative familial cancers that are autosomally dominant inherited disorders. Because endometrial cancers develop at high rates in women with HNPCC, it is suggested that some endometrial cancers are familial cancers that are induced by mutations of the DNA mismatch repair (MMR) genes, as in HNPCC. To understand the clinical pathology of familial endometrial cancers that are associated with HNPCC, we surveyed the family histories of 385 patients with endometrial cancer and found that 0.5% of endometrial cancers met the new diagnostic criteria of HNPCC. From molecular and biological analyses, we found microsatellite instability in 30.8% of endometrial cancers and germline mutations of MMR genes in 8.3%. These results suggest a close relationship of MMR gene mutations to the development of endometrial cancers. For a better understanding of the clinical pathology of HNPCC-associated familial endometrial cancers, it is critical for gynecologists to perform a large multicenter study, including detailed family histories.

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Dominant human papillomavirus 16 infection in cervical neoplasia in young Japanese women; study of 881 outpatients

Masumoto Nobuo, Fujii Takuma, Ishikawa Mitsuya, Mukai Makio, Ono Akiko, Iwata Takashi, Kubushiro Kaneyuki, Nozawa Shiro

Gynecologic Oncology 94 ( 2 ) 509 - 514 2004.08

ISSN 0090-8258

Objective. Human papillomavirus (HPV) infection is reported to be related to carcinogenesis in the uterine cervix. In Japan, screening for cervical cancer by cytology is performed in women over 30 years old. The purpose of this study was to determine whether there is an association between patient age and cervical neoplasia or HPV infection in Japanese women. Methods. Specimens from 881 randomly selected patients who came to our clinic were tested for HPV DNA by using Hybrid Capture II, whereas specimens from a 204-patient randomly selected subset diagnosed with cervical neoplasia were tested for HPV DNA by using polymerase chain reaction (PCR). HPV typing was performed in all the PCR-positive cases. Results. The HPV-positive rate in the 20- to 29-year-old patients (29.0% in the normal cytology/histology group and 85.5% in the abnormal group) was higher than in the 30- to 59-year-old patients, and the rate declined until age 60 when age increased. While HPV 18, HPV 52, other HPV types, and HPV types as a whole were frequently detected in 30- to 49-year-old patients, HPV 16 was detected more frequently in the younger group than the other HPV types (P = 0.03). Among the HPV 16-positive patients with cervical neoplasia, the proportion of cervical intraepithelial neoplasia (CIN) 3 cases was high (44%) in the 20- to 29-year-old group. Conclusions. Screening for cervical neoplasia by cytology should also be performed in women under 30 years old in Japan. The HPV typing could be a tool to strictly follow-up younger women who were diagnosed with CIN. © 2004 Elsevier Inc. All rights reserved.

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Association of HNPCC and endometrial cancers

Banno, K., Susumu, N., Yanokura, M., Hirao, T., Iwata, T., Hirasawa, A., Aoki, D., Sugano, K. and Nozawa, S.

Int J Clin Oncol 9 ( 4 ) 262 - 9 2004.08

ISSN 1341-9625

Hereditary nonpolyposis colorectal cancer (HNPCC) is among the representative familial cancers that are autosomally dominant inherited disorders. Because endometrial cancers develop at high rates in women with HNPCC, it is suggested that some endometrial cancers are familial cancers that are induced by mutations of the DNA mismatch repair (MMR) genes, as in HNPCC. To understand the clinical pathology of familial endometrial cancers that are associated with HNPCC, we surveyed the family histories of 385 patients with endometrial cancer and found that 0.5% of endometrial cancers met the new diagnostic criteria of HNPCC. From molecular and biological analyses, we found microsatellite instability in 30.8% of endometrial cancers and germline mutations of MMR genes in 8.3%. These results suggest a close relationship of MMR gene mutations to the development of endometrial cancers. For a better understanding of the clinical pathology of HNPCC-associated familial endometrial cancers, it is critical for gynecologists to perform a large multicenter study, including detailed family histories.

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【子宮頸癌・子宮体癌・卵巣癌の診断と治療　最新の研究動向】　子宮頸癌　子宮頸癌の治療　手術概論

久布白, 兼行, 岩田, 卓 and 野澤, 志朗

日本臨床 62 ( 増刊10 子宮頚癌・子宮体癌・卵巣癌の診断と治療 ) 134 - 140 2004

ISSN 0047-1852

Surgical treatment for cervical cancer

Kubushiro Kaneyuki, Iwata Takashi, Nozawa Shiro

Nippon rinsho. Japanese journal of clinical medicine 62 Suppl 10 134 - 140 2004

ISSN 0047-1852

腫瘍マーカー　婦人科分野の腫瘍マーカー

岩田, 卓, 塚崎, 克己 and 野澤, 志朗

Drug Delivery System 19 ( 2 ) 133 - 135 2004

ISSN 0913-5006

p16^INK4a overexpression and human papillomavirus infection in small cell carcinoma of the uterine cervix

Masumoto Nobuo, Fujii Takuma, Ishikawa Mitsuya, Saito Miyuki, Iwata Takashi, Fukuchi Takeshi, Susumu Nobuyuki, Mukai Makio, Kubushiro Kaneyuki, Tsukazaki Katsumi, Nozawa Shiro

Human Pathology 34 ( 8 ) 778 - 783 2003.09

ISSN 0046-8177

Carcinogenesis of cervical cancer has been investigated, and p16 ^INK4a overexpression in squamous cell carcinoma of the cervix has been reported as a result of infection by human papillomavirus (HPV) (eg, HPV 16), and the consequence of the retinoblastoma (Rb) protein inactivation by HPV E7 protein. However, to our knowledge, there have been no studies on the relation between p16^INK4a overexpression associated with HPV and small cell carcinoma of the cervix, which behaves more aggressively clinically than squamous cell carcinoma. The purpose of this study was to determine whether p16^INK4a is overexpressed in small cell carcinoma, and if p16^INK4a is overexpressed, the types of HPV that are related to this cancer. We reviewed 10 cases of small cell carcinoma and examined them for p16^INK4a overexpression by immunohistochemistry. We also performed HPV typing with polymerase chain reaction (PCR)-sequencing analysis and in situ hybridization and found that p16^INK4a was overexpressed in every case. PCR-sequencing analyses revealed that all cases were HPV-positive and that 9 cases were positive for HPV 18. Five of the 9 cases positive for HPV 18 were also positive by in situ hybridization and yielded a punctate signal, considered to represent the integrated form. In conclusion, p16^INK4a was overexpressed and HPV 18 was frequently detected in an integrated form in small cell carcinoma. Therefore, inactivation of Rb protein by HPV 18 E7 protein may be associated with carcinogenesis of small cell carcinoma the same as inactivation of Rb protein by HPV 16 E7 protein is associated with carcinogenesis of squamous cell carcinoma. © 2003 Elsevier Inc. All rights reserved.

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P16 overexpression and human papillomavirus infection in small cell carcinoma of the uterine cervix

Masumoto, N., Fujii, T., Ishikawa, M., Saito, M., Iwata, T., Fukuchi, T., Susumu, N., Mukai, M., Kubushiro, K., Tsukazaki, K. and Nozawa, S.

Hum Pathol 34 ( 8 ) 778 - 83 2003.08

ISSN 0046-8177

Carcinogenesis of cervical cancer has been investigated, and p16(INK4a) overexpression in squamous cell carcinoma of the cervix has been reported as a result of infection by human papillomavirus (HPV) (eg, HPV 16), and the consequence of the retinoblastoma (Rb) protein inactivation by HPV E7 protein. However, to our knowledge, there have been no studies on the relation between p16(INK4a) overexpression associated with HPV and small cell carcinoma of the cervix, which behaves more aggressively clinically than squamous cell carcinoma. The purpose of this study was to determine whether p16(INK4a) is overexpressed in small cell carcinoma, and if p16(INK4a) is overexpressed, the types of HPV that are related to this cancer. We reviewed 10 cases of small cell carcinoma and examined them for p16(INK4a) overexpression by immunohistochemistry. We also performed HPV typing with polymerase chain reaction (PCR)-sequencing analysis and in situ hybridization and found that p16(INK4a) was overexpressed in every case. PCR-sequencing analyses revealed that all cases were HPV-positive and that 9 cases were positive for HPV 18. Five of the 9 cases positive for HPV 18 were also positive by in situ hybridization and yielded a punctate signal, considered to represent the integrated form. In conclusion, p16(INK4a) was overexpressed and HPV 18 was frequently detected in an integrated form in small cell carcinoma. Therefore, inactivation of Rb protein by HPV 18 E7 protein may be associated with carcinogenesis of small cell carcinoma the same as inactivation of Rb protein by HPV 16 E7 protein is associated with carcinogenesis of squamous cell carcinoma.

P16^INK4aoverexpression and human papillomavirus infection in small cell carcinoma of the uterine cervix

Masumoto Nobuo， Fujii Takuma， Ishikawa Mitsuya， Saito Miyuki， Iwata Takashi， Fukuchi Takeshi， Susumu Nobuyuki， Mukai Makio， Kubushiro Kaneyuki， Tsukazaki Katsumi， Nozawa Shiro

Human Pathology 34 ( 8 ) 778-783 2003.08

Research paper (scientific journal), Joint Work

遺伝性子宮内膜癌とは−特にDNAミスマッチ修復遺伝子について

阪埜浩司，進　伸幸，矢野倉恵，平尾　健，岩田　卓，平沢　晃，青木大輔，野澤志朗

産婦人科の世界 55 ( 8 ) 863-870 2003.08

Research paper (scientific journal), Joint Work

Papanicolaou tests and molecular analyses using new fluid-based specimen collection technology in 3000 Japanese women

Masumoto N., Fujii T., Ishikawa M., Mukai M., Saito M., Iwata T., Fukuchi T., Kubushiro K., Tsukazaki K., Nozawa S.

British Journal of Cancer 88 ( 12 ) 1883 - 1888 2003.06

ISSN 0007-0920

A fluid-based Papanicolaou test has been established to improve sample collection and preparation. This study was the first largescale investigation in Japan to examine the feasibility of using fluid-based Papanicolaou specimens to detect human papillomavirus (HPV) using Hybrid Capture II and polymerase chain reaction (PCR). Three thousand patients who visited Keio University Hospital between October 2000 and February 2001 were enrolled in the study. The results of the fluid-based Papanicolaou tests corresponded well with those of conventional Papanicolaou smears (96.8% concordance). The sensitivities of cervical neoplasia detection using the fluid-based Papanicolaou test (73.9%) and Hybrid Capture II (76.3%, P=0.55) were not significantly different. Among the cervical intraepithelial neoplasia 3 and squamous cell carcinoma specimens, HPV 16 and HPV 52 were predominantly detected using the PCR method. Although some DNA samples extracted from the fluid-based specimens were degradaded, PCR and direct sequencing could be performed without difficulty even after 1 year of specimen storage. We conclude that fluid-based Papanicolaou specimens can be applied to investigate HPV infection. © 2003 Cancer Research UK.

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Papanicolaou tests and molecular analyses using new fluid-based specimen collection technology in 3000 Japanese women

Masumoto, N., Fujii, T., Ishikawa, M., Mukai, M., Saito, M., Iwata, T., Fukuchi, T., Kubushiro, K., Tsukazaki, K. and Nozawa, S.

Br J Cancer 88 ( 12 ) 1883 - 8 2003.06

ISSN 0007-0920

A fluid-based Papanicolaou test has been established to improve sample collection and preparation. This study was the first large-scale investigation in Japan to examine the feasibility of using fluid-based Papanicolaou specimens to detect human papillomavirus (HPV) using Hybrid Capture II and polymerase chain reaction (PCR). Three thousand patients who visited Keio University Hospital between October 2000 and February 2001 were enrolled in the study. The results of the fluid-based Papanicolaou tests corresponded well with those of conventional Papanicolaou smears (96.8% concordance). The sensitivities of cervical neoplasia detection using the fluid-based Papanicolaou test (73.9%) and Hybrid Capture II (76.3%, P=0.55) were not significantly different. Among the cervical intraepithelial neoplasia 3 and squamous cell carcinoma specimens, HPV 16 and HPV 52 were predominantly detected using the PCR method. Although some DNA samples extracted from the fluid-based specimens were degradaded, PCR and direct sequencing could be performed without difficulty even after 1 year of specimen storage. We conclude that fluid-based Papanicolaou specimens can be applied to investigate HPV infection.

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Papanicolaou tests and molecular analyses using new fluid-based specimen collection technology in 3000 Japanese women

Masumoto Nobuo， Fujii Takuma， Ishikawa Mitsuya，　Mukai Makio， Saito Miyuki， Iwata Takashi， Fukuchi Takeshi， Kubushiro Kaneyuki， Tsukazaki Katsumi， Nozawa Shiro

British Journal of Cancer 88 1883-1888 2003.06

Research paper (scientific journal), Joint Work

HNPCCの診療と研究遺伝性非腺腫症性大腸癌(HNPCC)と子宮内膜癌

阪埜浩司，進　伸幸，平尾　健，岩田　卓，平沢　晃，青木大輔，野澤志朗

家族性腫瘍 3 ( 2 ) 62-67 2003.05

Research paper (scientific journal), Joint Work

子宮体癌におけるMicrosatellite Instability(MSI)の検出に免疫組織化学は有用か?

進, 伸幸, 青木, 大輔, 阪埜, 浩司, 平尾, 健, 平沢, 晃, 岩田, 卓, 鈴木, 直, 菅野, 康吉, 向井, 万起男 and 野澤, 志朗

日本婦人科腫瘍学会雑誌 21 ( 3 ) 208 2003

ISSN 1347-8559

【HNPCCの診療と研究】　遺伝性非腺腫症性大腸癌(HNPCC)と子宮内膜癌

阪埜, 浩司, 進, 伸幸, 平尾, 健, 岩田, 卓, 平沢, 晃, 青木, 大輔 and 野澤, 志朗