Misc - SAITOU Tsuyoshi

Usefulness of silver intensification of immunostaining for cytologic diagnosis of primary melanoma of the female genital organs

T Saito, M Takehara, R Tanaka, K Sato, M Fujita, R Kudo

ACTA CYTOLOGICA ( SCI PRINTERS & PUBL INC )  46 ( 6 ) 1075 - 1080  2002.11

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OBJECTIVE: To improve the procedure for diagnosing vaginal melanoma with cytopathologic analysis of HMB-45. STUDY DESIGN: The study examined silver intensification of immunostaining of HMB-45 in nine cases of primary melanoma of the vagina and vulva using archival Papanicolaoustained smears. RESULTS: All nine samples showed positive staining for HMB-45. Five cases showed intensive staining, two moderate and two weak. The positive staining was black in the cytoplasm of melanoma cells but was detected in neither the background nor normal squamous cells. Though destaining of Papanicolaou stain was not performed before immunostaining, the positivity of immunostaining was easily judged. CONCLUSION: After morphologic observation, immunocytochemical study of HMB-45 is possible even though time has passed since the cytologic specimen was obtained. When there is a suspicion of amelanotic melanoma or scantily pigmented melanoma of the vagina and vulva, cytogenesis with HMB-45 is helpful, especially because it involves little invasion.

Imaging studies in patients with malignant melanoma in the female genital tract

M Takehara, T Saito, H Mizumoto, T Baba, R Tanaka, T Fujimoto, K Adachi, R Kudo

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER ( BLACKWELL PUBLISHING INC )  12 ( 5 ) 506 - 509  2002.09

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The purpose of this study was to review magnetic resonance imaging (MRI) and pathologic features of primary malignant melanoma (melanoma) in the female genital tract. We retrospectively evaluated MRI in six women with melanoma of the genital tract. The signal intensity of the tumor on T1-weighted images (WI) was compared with the amount of melanin granules in hematoxylin-eosin stained sections of resected specimen. On T1WI, four melanomas showed a high signal intensity, one intermediate, and one low. The four melanomas with a high signal intensity on T1W1 were rich in melanin granules, while the one intermediate tumor had few granules. The other one was amelanotic. We believe that a high signal on T1WI is characteristic of primary melanotic melanoma of the female genital tract. Our findings suggest that it is strongly influenced by the presence of melanin granules.

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Acceleration of invasive activity via matrix metalloproteinases by transfection of the estrogen receptor-alpha gene in endometrial carcinoma cells

H Mizumoto, T Saito, K Ashihara, M Nishimura, R Tanaka, R Kudo

INTERNATIONAL JOURNAL OF CANCER ( WILEY-LISS )  100 ( 4 ) 401 - 406  2002.08

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It is well known that the functions of reproductive organs are regulated by sex steroids and their receptors and it is hypothesized that the progression of neoplasms that originate from the reproductive organs is influenced by them. However, the correlation between sex steroids and tumor progression, especially tumor invasion, is not well known in endometrial carcinoma. In our study, we focused on the influence of estrogen and its receptor in invasion and matrix metalloproteinases (MMI's), which are known to be important in tumor invasion, as well as on endometrial carcinoma cells. The growth of Ishikawa, cells, to which an estrogen receptor-alpha expressing vector was transfected, was accelerated by 17beta-estradiol as was the acceleration of the expression of cyclin D1. By invasion assay, in conditions with 17beta-estradiol, the invasiveness of Ishikawa cells was enhanced. Furthermore, according to the accelerated invasiveness, the expression of MMP-1, -7 and -9 and Ets-1 was enhanced. These results suggest that activation of ER-alpha by estrogen results in tumor progression by stimulating cell growth and invasiveness via acceleration of the expression of MMPs. (C) 2002 Wiley-Liss, Inc.

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Loss of gamma-catenin expression in squamous differentiation in endometrial carcinomas

K Ashihara, T Saito, H Mizumoto, K Adachi, R Tanaka, M Nishimura, E Ito, R Kudo

INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY ( LIPPINCOTT WILLIAMS & WILKINS )  21 ( 3 ) 246 - 254  2002.07

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Squamous differentiation occurs in 25 to 50% of endometrial endometrioid adenocarcinomas. In this study, we analyzed the immunohistochemical expression and localization of beta- and gamma-catenin, molecular changes in the beta-catenin gene, and the subcellular localization of the desmosomal component protein, desmoplakin, by laser scanning microscopy in 35 endometrial carcinomas with squamous differentiation. In the glandular component, beta-catenin showed nuclear localization in 10 of 35 (28.5%) samples, whereas in the squamous component, nuclear localization was found in 15 of 35 (42.9%). Of the 15 samples that showed nuclear localization of beta-catenin in the squamous component, seven samples (46.7%) did not express gamma-catenin. The phenomenon was not correlated with mutation in exon 3 region of beta-catenin gene. Furthermore. in these samples, there was diffuse cytoplasmic staining for desmoplakin. These observations have not been reported in other tumors. Our results suggest that unique molecular events. i.e., stimulation of beta-catenin and suppression of gamma-catenin expression. occur within endometrial carcinomas with squamous differentiation.

Expression of matrix metalloproteinases in ovarian endometriomas: immunohistochemical study and enzyme immunoassay

H Mizumoto, T Saito, K Ashihara, M Nishimura, M Takehara, R Tanaka, E Ito, R Kudo

LIFE SCIENCES ( PERGAMON-ELSEVIER SCIENCE LTD )  71 ( 3 ) 259 - 273  2002.06

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Like carcinoma, endometriosis has the unique characteristics, of invasion and metastasis, though pathologically, it is a benign tumor. However, the mechanism of destruction of the surrounding tissue in endometriosis is still unclear. In this study, the expression and localization of matrix metalloproteinases (MMP)-1, -2, -3, -7, -9 and tissue inhibitors of metalloprotemases-1 (TIMP-1) were evaluated by immunohistochemistry for 20 cases and the amounts of MMP-1, TIMP-1 and MMP-1/TIMP-1 complex in the fluid of endometrioma, were analyzed by ELISA and western blotting for 20 cases, which were analyzed by immunohistochemical study. MMP-1, -2 and -9 were detected strongly in both stromal and epithelial cells and MMP-7 in the epithelial cells in the menstrual period. MMP-3 was mainly expressed in macrophage containing hemosiderin but the change of expression was not clear. TIMP-1 was intensively detected in both stromal and epithelial cells in the menstrual period but the expression decreased in other stages of the menstrual cycle. ELISA for MMP-1 also showed results similar to immunohistochemistry, suggesting that it was released to the cyst in the menstrual period when it was released to the extracellular space from the cytoplasm. The expression of TIMP-I was not clearly changed during the menstrual cycle. From these results, it was suggested that the destruction of the surrounding matrix by endometriosis might be caused by various MMPs, which are mainly produced in stromal cells. (C) 2002 Elsevier Science Inc. All rights reserved.

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Mutation of β-catenin gene in endometrial cancer but not in associated hyperplasia

Koji Ashihara, T. Saito, Hisanobu Mizumoto, Makoto Nishimura, Ryoichi Tanaka, Ryuichi Kudo

Medical Electron Microscopy   35 ( 1 ) 9 - 15  2002

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Endometrial hyperplasia is a recognized effect of excessive or unopposed estrogen stimulation and is considered to be a precancerous condition of endometrial adenocarcinoma. We have previously shown that the subcellular localization of β-catenin in the human endometrium is changed according to cell proliferation, suggesting a role of intercellular transduction in cell-growth control in human endometrium, not only in the physiological condition but also in the carcinogenic endometrium. In the present study, to clarify at which stage of endometrial carcinogenesis molecular alteration of the β-catenin gene occurs, we analyzed the subcellular localization of β-catenin by immunohistochemistry, and we analyzed exon 3 of the β-catenin gene, in 25 patients - with endometrial hyperplasia and 20 patients with endometrial cancers associated with endometrial hyperplasia, digesting DNA from the cancer and hyperplasia parts, separately. Fourteen of the 25 (56.0%) endometrial hyperplasia samples, 12 (60.0%) endometrial cancers, and 11 (55.0%) associated hyperplasias of the 20 endometrial cancers associated with hyperplasia showed nuclear localization of β-catenin. Mutation in exon 3 of the β-catenin gene was found in 2 of the 20 endometrial cancer samples however, it was not found in the 25 endometrial hyperplasias or the 20 associated hyperplasias. The results suggest that molecular alteration of the β-catenin gene occurs in atypical hyperplasia or cancer, rather than in simple or complex hyperplasia without atypia, during endometrial carcinogenesis.

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Hemorrhagic infarction of fibroma: MR imaging appearance

M. Takehara, T. Saito, K. Manase, T. Suzuki, T. Hayashi, R. Kudo

Archives of Gynecology and Obstetrics   266 ( 1 ) 48 - 49  2002

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We experienced a case of hemorrhagic infarction of the ovarian fibroma and that indicated the characteristic following appearance: exhibiting a high signal intensity area observed at the periphery of mass on T1-weighted MRI (magnetic resonance imaging). It was thought that this appearance developed because hemorrhagic infarction was caused by subacute ovarian torsion. This is a useful finding for suspecting hemorrhagic infarction preoperatively.

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Suppressed gap junctional intercellular communication in carcinogenesis of endometrium

T Saito, M Nishimura, R Kudo, H Yamasaki

INTERNATIONAL JOURNAL OF CANCER ( WILEY-LISS )  93 ( 3 ) 317 - 323  2001.08

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To examine whether and at which stage of endometrial carcinogenesis decreased connexin expression occurs, we investigated changes in the expression of the gap junction proteins, connexin 26 (Cx26), Cx32 and Cx43, in human endometrial hyperplasia and cancer samples. Forty-eight endometrial tissue samples (15 endometrial hyperplasias and 33 endometrial cancers) were subjected to immunofluorescence and RT-PCR analysis, In endometrial hyperplasia, Cx26 war aberrantly expressed in all samples as revealed immunohistochemically. There was weak or negative expression in 12 samples (80.0%) and diffuse expression in cytoplasm in 3 samples (20.0%), Cx32 expression in those samples was similar to that of Cx26; there was weak or negative expression in II samples (73.3%) and diffuse expression in 4 samples (26.7%), In endometrial cancer, Cx26 was expressed weakly or negatively in 25 samples (75.8%), diffusely in 6 samples (18.2%) and normally in 2 samples (6.1%), while Cx32 was expressed weakly or negatively in 26 samples (78.8%), diffusely in 5 samples(15.2%) and normally in 2 samples (6.1%). It was confirmed that weak staining of Cx26 and Cx32 was due to poor expression of their mRNA, All samples showed weak Cx43 protein expression as revealed by immunohistochemical analysis, In the majority of samples, concomitant expression levels of Cx26 and Cx32 protein were observed, confirming our long-term hypothesis that Cx26 and Cx32 are both abnormally regulated in a coordinated fashion in the endometrium, Our results indicate that during endometrial carcinogenesis, loss of gap junctional intercellular communication (GJIC) may occur due to the suppressed expression and the aberrant localization of connexin at relatively early stages. (C) 2001 Wiley-Liss, Inc.

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Conservative vaginal surgery for cervical pregnancy

N Akutagawa, A Nishikawa, T Saito, S Sagae, R Kudo

BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY ( ELSEVIER SCIENCE BV )  108 ( 8 ) 888 - 889  2001.08

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Changes in expression and subcellular localization of nuclear retinoic acid receptors in human endometrial epithelium during the menstrual cycle

K Fukunaka, T Saito, K Wataba, K Ashihara, E Ito, R Kudo

MOLECULAR HUMAN REPRODUCTION ( OXFORD UNIV PRESS )  7 ( 5 ) 437 - 446  2001.05

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The endometrium is a uniquely dynamic tissue in that it undergoes monthly cycles of proliferation and secretory activity, and is regulated by ovarian steroid hormones. In this study, we focused on retinoic acid receptors (RAR and RXR) which are ligand-dependent transcription factors belonging to the large family of steroid hormones and are expected to affect to cell growth and differentiation in the endometrium. We analysed the expression and subcellular localization of the RA receptors in 57 samples of human endometrium by immunohistochemistry and Western blotting. In the nuclei of the endometrial epithelium, the RA receptors were expressed strongly in the proliferative phase, However, RAR were drastically reduced in the epithelial nuclei during the secretory phase in association with changes in serum oestradiol and in the expression of the oestrogen receptor. The expression of RXR was localized in the epithelial nuclei throughout the menstrual cycle. Confocal laser scanning microscopical observation clearly showed the difference in the localization between RAR and RXR in the secretory phase. Furthermore the findings of immune-electron microscopy showed pooled RAR around the rough endoplasmic reticulum, suggesting that transport of these receptors to the nuclei is inhibited. These findings suggest that RAR and RXR work mainly in the proliferative phase and that in the endometrium RXR may play a different role to RAR during the secretory phase.

Postoperative Infections after Hysterectomy and the Efficacy of Prophylactic Antiboitics

J Gynecol Tech   6   107 - 110  2001

産後15ヵ月で発見された子宮内膜癌の1例

石岡 伸一, 寒河江 悟, 斎藤 豪, 杉村 政樹, 芥川 典之, 西村 誠, 江坂 嘉昭, 工藤 隆一

The Journal of Obstetrics and Gynaecology Research ( John Wiley & Sons Australia, Ltd )  26 ( 6 ) 417 - 420  2000.12

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25歳,一妊一産で1997年10月に妊娠40週にて女児分娩した.妊娠経過及び出産時の異常は認めていない.産後7ヵ月より月経発来し,その後ほぼ30日周期で順調に発来していた.産後15ヵ月に不正出血を主訴に近医受診し,子宮内膜細胞診V型,内膜組織診にて類内膜腺癌と診断された.入院後,準広汎子宮全摘出術,両側付属器摘出術,骨盤内リンパ節郭清術を施行し,子宮内膜癌Ib期と診断された.術後経過は順調で現在まで再発徴候を認めていない.本症例は肥満,糖尿,月経不順といった子宮内膜癌の危険因子と考えられる因子はもたず,産後比較的早期に発生した若年性の原発性子宮内膜癌であった

HMB-45 staining for cytology of primary melanoma of the vagina - A case report

M Takehara, E Ito, T Saito, Y Nishioka, K Ashihara, S Yamashita, M Koizumi, R Kudo

ACTA CYTOLOGICA ( SCI PRINTERS & PUBL INC )  44 ( 6 ) 1077 - 1080  2000.11

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BACKGROUND: Malignant melanoma in the vagina is very rare, but its diagnosis is usually easy if a melanin pigment is present. With cytodiagnosis, however, it is difficult to differentiate amelanotic melanoma or scantily pigmented melanoma from other conditions. In the present case, monoclonal antibody HMB-45, the efficacy of which has been established in histologic studies, was used in the cytodiagnosis of amelanotic melanoma in the vagina. CASE: A woman, aged 78 years, presented with a brownish, nodular tumor, diameter 3 cm, in the vagina. Scraping smears with Papanicolaou staining showed nonepithelial malignant cells without granules suggesting melanin. Smears stained with HMB-45 showed positive immunoreactivity. The diagnosis underwent histologic confirmation of amelanotic melanoma on the initial biopsy. CONCLUSION: Cytodiagnosis was made with HMB-45, which proved very effective in the differential cytodiagnosis of amelanotic melanoma and scantily pigmented melanoma, particularly because it obviated the need for tissue invasion.

Human hemangiosarcomas have a common polymorphism but no mutations in the connexin37 gene

T Saito, Krutovskikh, V, MJ Marion, KG Ishak, WP Bennett, H Yamasaki

INTERNATIONAL JOURNAL OF CANCER ( WILEY-LISS )  86 ( 1 ) 67 - 70  2000.04

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Gap junctional intercellular communication is often impaired in cancers, and the genes which encode the connexin gap junction proteins are considered to be tumor-suppressor genes. In this study, we analyzed the presence of mutations in the connexin 37 (Cx37) gene in 22 human hepatic angiosarcomas, 6 and 4 of which were associated with exposure to vinyl chloride and Thorotrast, respectively, The other 12 samples were from patients with no history of exposure to these 2 agents. In 9 samples, a proline (ACC) to serine (ACT) amino acid change in codon 319 was detected. However, DNA from non-tumorigenic tissue of the same patients also showed this amino acid change, suggesting that this is a polymorphism rather than a mutation. Subsequent analysis of 84 DNA samples from normal donors revealed the frequencies of Pro/Pro, Pro/Ser and Ser/Ser alleles to be 65.5%, 23.8% and 10.7%, respectively, while among the group of angiosarcoma patients the corresponding figures were 59.1%, 31.8% and 9.1%, respectively. Thus, there was no correlation between the polymorphism at codon 319 and hepatic angiosarcoma occurrence. However, among the 6 cases of vinyl chloride-associated angiosarcoma, the percentages of the polymorphic alleles were 33.3%, 66.7% and 0%, respectively. While the number of samples was too small to allow us to conclude that the Ser(319) allele in Cx37 predisposes to this rare type of human cancer, it may be noted that codon 319 is located at the cytoplasmic tail of Cx37, where most regulatory sequences reside, and that it could be a site of phosphorylation for some protein kinases, which may in turn affect the function of Cx37, including intercellular communication, Int. J. Cancer 86:67-70, 2000. (C) 2000 Wiley-Liss, Inc.

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婦人科悪性腫瘍の化学療法における悪心・嘔吐に対する経口5-HT3受容体拮抗薬の効果と問題点

石岡 伸一, 寒河江 悟, 斎藤 豪, 木谷 保, 杉村 政樹, 芥川 典之, 梅村 康太, 伊東 英樹, 工藤 隆一

癌と化学療法 ( (株)癌と化学療法社 )  27 ( 4 ) 593 - 598  2000.04

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婦人科癌化学療法に対する4種類の経口5-HT3受容体拮抗薬,granisetron,ramosetron,ondansetron,tropisetronの効果をgranisetron注射薬と比較検討した.内服薬間で効果の有意な差はなく,JT療法(paclitaxel+carboplatin),paclitaxel単独療法では内服薬でも抗癌剤投与後5日間にわたり十分な効果を示した.一方,CAP療法では内服薬では効果不十分で,注射薬の使用が望ましいと考えられた

A new technique for radical hysterectomy with emphasis on preservation of bladder function

E. Ito, R. Kudo, T. Saito, M. Koizumi, M. Noda

Journal of Gynecologic Surgery ( Mary Ann Liebert Inc. )  16 ( 4 ) 133 - 140  2000

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Bladder dysfunction always occurs, to varying degrees, following radical hysterectomy. In Japan, various techniques for preserving the pelvic autonomic nerves in a radical hysterectomy have been used to reduce the severity of bladder dysfunction. The authors describe a newly developed technique for preserving the pelvic autonomic nerves and present the postoperative urodynamic findings in cases in which this technique was used. Preservation techniques can be broadly classified into three types: preservation of the pelvic parasympathetic nerves, preservation of the pelvic sympathetic nerves, and preservation of the nerves to the bladder. In this new technique, as many of the pelvic parasympathetic nerves as possible are preserved when the cardinal ligament is cut. Then, the cardinal ligament is inserted into and pulled through the anterocranially located connective tissue in front of the pelvic plexus, which lies below the ureter. Finally, as many as possible of the vesical branching nerves are preserved when the posterior layer of the vesicouterine ligament is cut. Between July 1996 and February 1999, 23 women were treated for Stage IB1-IIA cervical cancer, and two women were treated for Stage IIB endometrial cancer. The results of urodynamic studies performed ∼1 month after surgery were all within normal ranges: mean duration of bladder drainage, 17.1 ± 6.4 days mean maximal flow rate, 19.5 ± 12.9 ml/sec mean postvoiding residual urine volume, 30.5 ± 25.8 ml and mean maximal desire to void, 311.4 ± 124.0 ml. None of the patients required intermittent self-catheterization. It is concluded that this new technique for preservation of the pelvic autonomic nerves is effective in reducing the severity of bladder dysfunction after a radical hysterectomy and would therefore improve the patient's quality of life.

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A case of a screlosing stromal ovarian tumor that expresses VEGF

Shin-Ichi Ishioka, Satoru Sagae, Tsuyoshi Saito, Tamotsu Kiya, Noriyuki Akutagawa, Masaki Sugimura, Ryuichi Kudo

Journal of Obstetrics and Gynaecology Research ( University of Tokyo Press )  26 ( 1 ) 35 - 38  2000

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A case of a sclerosing stromal tumor (SST) of the ovary is presented. One of the tumor's characteristics was its high vascularity. On immunohistochemical staining, the vascular endothelial growth factor (VEGF) was positive for both cellular and edematous areas in the tumor. VEGF was thought to be a factor that affected the clinicopathological features of this tumor.

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A case of uterine endometrial carcinoma 15 months post-partum

S. I. Ishioka, S. Sagae, T. Saito, M. Sugimura, N. Akutagawa, M. Nishimura, Y. Ezaka, R. Kudo

Journal of Obstetrics and Gynaecology Research ( University of Tokyo Press )  26 ( 6 ) 417 - 420  2000

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A case of uterine endometrial carcinoma 15 months post-partum, who did have none of typical risk factors of uterine endometrial carcinoma, is presented. The occurrence of post-partum uterine endometrial carcinoma is extremely rare condition probably due to anti-carcinogenic effects of progesterone. Progesterone refractory cells in the uterine endometrium, which could be an origin of the endometrial carcinoma, might have existed.

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[Effects of oral 5-HT3 antagonists on chemotherapy-induced emesis in patients with gynecologic cancers]

Gan To Kagaku Ryoho   27   593 - 8  2000

A case of Stage-IVb cervical adenocarcinoma successfully treated by combination chemotherapy: Case report

Masaki Takehara, Yoshihiro Nishioka, Tsuyoshi Saito, Tsuyoshi Baba, Takahiro Suzuki, Eiki Ito, Ryuichi Kudo

Journal of Obstetrics and Gynaecology Research ( University of Tokyo Press )  26 ( 2 ) 133 - 136  2000

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A 54-year-old patient with a Stage IVb adenocarcinoma of the cervix was treated with combination chemotherapy. This regimen consisted of intravenous cisplatin (70 mg/m2) and aclacinomycin A (30 mg/m2) on Day 1, followed by mitomycin C (5 mg/m2) on Day 2 and 3. A pathologically complete response was achieved by this regimen. The patient is well and has been free of symptoms for 66 months.

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