研究者詳細 - 山上　亘

論文 - 山上　亘

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Trends and characteristics of fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer in Japan: a survey by the Gynecologic Oncology Committee of the Japan Society of Obstetrics and Gynecology

Ushijima K., Tsuda N., Yamagami W., Mitsuhashi A., Mikami M., Yaegashi N., Enomoto T.

Journal of Gynecologic Oncology （Journal of Gynecologic Oncology） 34 （ 3 ） e38 2023年05月

ISSN 20050380

Objective: The objective of this study was to examine the current trends in fertility-sparing (FS) treatment for young atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) patients in Japan. Methods: This study was conducted by the Committee on Gynecologic Oncology of the Japan Society of Obstetrics and Gynecology (JSOG) in the 2017–2018 fiscal year. A nationwide, retrospective questionnaire-style survey—as performed. We collected the data of 413 patients from 102 JSOG gynecological cancer registered institutions. Results: FS treatment was performed with medroxyprogesterone (MPA) (87.2%) or MPA + metformin (11.6%). Pathological complete remission (CR) after initial treatment was achieved in 78.2% of patients. The significant clinicopathological factors correlated to CR after initial treatment were histology (AEH vs. endometrioid carcinoma grade 1 [ECG1]), body mass index (BMI) (<25 vs. ≥25 kg/m2), and treatment period (<6 vs. ≥6 months). ECG1, time to complete remission (TTCR) ≥6 months, maintenance therapy (−), and pregnancy (−) were associated with a significantly higher risk of recurrence on multivariate analysis. The total pregnancy rate was 47%, and the live birth rate was 40.1%. Patients who received infertility treatments showed a higher live birth rate (50.6%) than those who did not (7.7%). Conclusion: In this survey, we confirmed that FS treatment in Japan is centered on MPA alone and in combination with metformin, and that the treatment efficacy is similar to that reported in previous reports. A multicenter survey study in Japan showed FS treatment for young AEH and EC patients in compliance with the indications is feasible.

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Obstetric outcomes after medroxyprogesterone acetate treatment for early stage endometrial cancer or atypical endometrial hyperplasia: a single hospital-based study

Oishi M., Kasuga Y., Fukuma Y., Hamuro A., Tamai J., Tanaka Y., Hasegawa K., Yoshimura T., Ikenoue S., Ochiai D., Yamagami W., Tanaka M.

International Journal of Clinical Oncology （International Journal of Clinical Oncology） 28 （ 4 ） 587 - 591 2023年04月

研究論文（学術雑誌）, ISSN 13419625

Background: To investigate perinatal outcomes in pregnancy after high-dose medroxyprogesterone acetate (MPA) therapy for early stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) and to determine whether pregnancy after MPA therapy is at a higher risk of placenta accreta. Methods: Data of 51 pregnancies in 46 women who received MPA therapy for EC or AEH and delivered after 22 weeks of gestation at Keio University Hospital were reviewed. A retrospective matched case–control study was performed to determine the risk of placenta accreta in pregnancy after MPA therapy compared with singleton pregnancies without any history of maternal malignancy treatments. Results: The incidence of placenta accreta was higher in the MPA group than in the control group (15.7 vs. 0%, p = 0.0058). However, no differences in other perinatal outcomes were observed between groups. While gestational weeks at delivery in the MPA group were later than those in the control group (p = 0.0058), no difference in the incidence of preterm delivery was recorded between groups. In the MPA therapy group, the number of patients who underwent ≥ 6 dilation and curettage (D&C) was higher in the placenta accreta group than in the non-placenta accreta group (50.0 vs. 14.0%, p = 0.018). Patients with ≥ 6 D&Cs demonstrated a 6.0-fold increased risk of placenta accreta (p = 0.043, 95% CI 1.05–34.1) than those receiving ≤ 3 D&Cs. Conclusion: Pregnancy after MPA therapy is associated with a high risk of placenta accreta. In cases in which the frequency of D&C is high, placenta accreta should be considered.

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更年期女性の精神症状に漢方薬を使用した10症例

谷本慧子，横田めぐみ，椎名美季，大野あゆみ，弟子丸亮太，岩田　卓，堀場裕子，青木大輔

産婦人科漢方研究のあゆみ 39 109 - 114 2023年04月

研究論文（学術雑誌）

月経前症候群・月経前不快気分障害に対する抑肝散・抑肝散加陳皮半夏の有用性

大野あゆみ，横田めぐみ，椎名美季，谷本慧子，弟子丸亮太，岩田　卓，青木大輔

産婦人科漢方研究のあゆみ 39 64 - 67 2023年04月

研究論文（学術雑誌）

更年期の動悸に苓桂朮甘湯を処方した12例の検討

横田めぐみ，椎名美季，大野あゆみ，谷本慧子，堀場裕子，弟子丸亮太，田中　守，青木大輔

産婦人科漢方研究のあゆみ 39 39 - 43 2023年04月

研究論文（学術雑誌）

子宮内膜異型増殖症の術前診断で腹腔鏡下手術を施行した症例の検討

平田桃, 坂井健良, 山上亘, 北澤晶子, 家谷佳那, 高橋美央, 吉村拓馬, 吉浜智子, 千代田達幸, 阪埜浩司, 田中守, 青木大輔

東京産科婦人科学会会誌 72 （ 2 ） 177 - 182 2023年04月

研究論文（学術雑誌）, 査読有り

Evaluation of the role of intraoperative frozen section and magnetic resonance imaging in endometrial cancer

Ooka R., Nanki Y., Yamagami W., Kawaida M., Nagai S., Hirano T., Sakai K., Makabe T., Chiyoda T., Kobayashi Y., Kataoka F., Aoki D.

International Journal of Gynecology and Obstetrics （International Journal of Gynecology and Obstetrics） 160 （ 2 ） 554 - 562 2023年02月

研究論文（学術雑誌）, 査読有り, ISSN 00207292

Objective: To evaluate the accuracy of preoperative endometrial biopsy and magnetic resonance imaging (MRI) of endometrial cancer compared with that of intraoperative frozen section. Methods: This retrospective study included 264 patients who underwent surgery with intraoperative frozen section for endometrial cancer at our institution between 2014 and 2018. Diagnosis was determined by histologic type, grade, and myometrial invasion. Concordance rate, sensitivity, and specificity of preoperative diagnosis and intraoperative frozen diagnosis were calculated, in comparison to the final pathologic diagnosis. Results: Preoperative and intraoperative diagnoses showed no statistically significant difference in determining histologic type and grade (P = 0.152). Intraoperative diagnosis showed higher sensitivity for endometrioid carcinoma grade 3 and other types, and higher specificity for grade 1. For myometrial invasion, intraoperative diagnosis showed significantly higher concordance rate than preoperative MRI findings (P < 0.01). Intraoperative diagnosis showed higher sensitivity and specificity in patients with and without myometrial invasion, respectively. Conclusion: Higher agreement between intraoperative and final diagnoses, especially in myometrial invasion, suggests that intraoperative frozen section is a good indicator for appropriate surgical procedure decision making.

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Evaluation of the one-step nucleic acid amplification assay for detecting lymph node metastasis in patients with cervical and endometrial cancer: A multicenter prospective study.

Togami S, Tanimoto A, Yanazume S, Tokunaga H, Nagai T, Watanabe M, Yahata H, Asanoma K, Yamamoto H, Tanaka T, Ohmichi M, Yamada T, Todo Y, Yamada R, Kato H, Yamagami W, Masuda K, Kawaida M, Niikura H, Moriya T, Kobayashi H

Gynecologic oncology （Gynecologic Oncology） 170 70 - 76 2023年01月

ISSN 0090-8258

Objective: This multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers. Methods: Surgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-μm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance. Results: A total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961–0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819–0.973) and 0.989 (95% CI: 0.973–0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance. Conclusions: The OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers.

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Case Series of Mayer–Rokitansky–Küster–Hauser Syndrome: Analysis of 17 Cases

Miyake A., Kobayashi Y., Imaeda K., Yoshihama T., Nakamura K., Yokota M., Hayashi S., Yamagami W., Banno K., Aoki D.

Clinical and Experimental Obstetrics and Gynecology （Clinical and Experimental Obstetrics and Gynecology） 50 （ 1 ） 2023年01月

ISSN 03906663

Background: The Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is a rare disorder characterized by congenital vaginal defects and uterine traces. Because of its rarity, standardized management for MRKH syndrome is unavailable. This study reviewed the management of the patients with MRKH syndrome in our institution. Methods: Using medical records, we retrospectively reviewed the surgical techniques, outcomes, postoperative management methods, and outpatient follow-up of 17 patients with MRKH syndrome in Keio University Hospital. Results: Of the 14 patients who requested vaginoplasty, 12 underwent surgery with Davydov’s modified procedure after the Frank method, and it took 17 months to 34 months (median two years) for the vaginal cavity to enlarge by 5–6 cm. The Frank method is a non-surgical dilation with instrumental stretching of the vaginal vestibular mucosa. Davydov’s procedure is a surgical vaginoplasty in which the vesicoureteral space is coated by the peritoneum. Although one patient lost 3800 mL of bleeding from the plexus vein and four needed to remove the prosthesis under anesthesia about one month after surgery, all patients achieved anatomic success with a vaginal cavity length of 6 cm or more and could have sexual intercourse with their sexual partners. However, two patients interrupted their preoperative hospital visits, and three were lost to follow-up postoperatively. Two of the three patients who did not accept vaginoplasty presented myoma at uterine trace and underwent myomectomy. Another one was scheduled for surgery through psychological support. Conclusions: Davydov’s modified procedure is effective, and dilating the vaginal cavity adequately using the Frank method before surgery is needed to ensure sufficient vaginal length with less perineum. During the operation, attention is required to care for the plexus vein. Comprehensive psychological support, providing appropriate information to the patient for mental maturity, and planning surgery according to their life stages are essential for successful treatment.

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Impact of adjuvant chemotherapy on the overall survival of patients with resectable bulky small cell neuroendocrine cervical cancer: a JSGO-JSOG joint study

Seino M., Nagase S., Ohta T., Yamagami W., Ebina Y., Kobayashi Y., Tabata T., Kaneuchi M., Enomoto T., Mikami M.

Journal of Gynecologic Oncology （Journal of Gynecologic Oncology） 34 （ 1 ） e4 - e4 2023年01月

研究論文（学術雑誌）, ISSN 20050380

Objective: The aim of this study was to review the clinicopathological characteristics of small cell neuroendocrine cervical cancer (SCNEC) and to identify the optimal treatment. Methods: The Japanese Society of Gynecologic Oncology conducted a retrospective cohort study of SCNECs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology between 2004 and 2015. All cases were modified and unified by International Federation of Gynecology and Obstetrics 2008 (Union for International Cancer Control 7th edition). Results: There were 822 registered patients diagnosed with SCNEC from 2004 to 2015 which comprised 1.1% (822/73,698) of all uterine cervical cancer cases. Rates of lymph-node and distant metastasis were significantly higher in T1b2 (38.9% and 13.7%, respectively) than T1b1 (14.2% and 4.4%, respectively) (p<0.01). In IB2 and T1bN1M0 SCNEC, the 5-year survival rate with surgery followed by chemotherapy was significantly higher than that with surgery followed by radiation therapy/concurrent chemoradiation therapy (p<0.01). Conclusion: SNCEC tumors >4 cm in size had greater rates of lymph-node and distant metastasis when compared with tumors ≤4 cm. Adjuvant chemotherapy, rather than radiotherapy, may improve prognosis after surgery in T1bN1M0 SCNEC.

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Impact of the COVID-19 pandemic on surgery for benign diseases in gynecology: A nationwide survey by the Japan Society of Obstetrics and Gynecology

Komatsu H., Nakagawa S., Yamagami W., Yamada H., Miyashita S., Yoshino K., Kawana K., Shibahara H., Hamatani T., Aoki D.

Journal of Obstetrics and Gynaecology Research （Journal of Obstetrics and Gynaecology Research） 49 （ 1 ） 314 - 320 2023年01月

研究論文（学術雑誌）, 共著, 責任著者, 査読有り, ISSN 13418076

Aim: This study aimed to clarify the impact of coronavirus disease 2019 on gynecology practice in Japan, in particular, on surgeries for benign gynecological diseases. Methods: An online questionnaire was distributed to 966 facilities in Japan, including core facilities, facilities participating in perinatal and gynecologic oncology registries, and facilities certified for training by the Japanese Society of Obstetrics and Gynecology Endoscopy. The number of surgeries performed was compared between 2019 and 2020, when the novel coronavirus disease was prevalent. Results: Five hundred and eighty (58.2%) facilities responded. The total number of surgeries decreased from 129 648 in 2019 to 118 565 in 2020, by 8.5%, for all surgical procedures. However, there was a clear increase in the number of robotic surgeries performed in 2020 compared to that in 2019 for all populations. The number of total hysterectomies decreased markedly from 15 385 in 2019 to 12 531 in 2020, a fall of 10.1%. Conclusions: The number of surgeries for benign gynecological diseases decreased by 8.5% in 2020 compared to that in 2019. This value is among the lowest in the world.

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Adenocarcinoma in situ or early-stage cervical cancer is a risk factor for preterm delivery after cervical conization: a multicenter observational study

Kasuga Y., Ikenoue S., Nishio H., Yamagami W., Ochiai D., Tanabe K., Tashima Y., Hirao N., Miyakoshi K., Kasai K., Suda Y., Nemoto T., Shiraishi S., Yoshida H., Kurahashi T., Takamatsu K., Iwasaki S., Yamashita H., Akiba Y., Arase T., Hara S., Nakada S., Tanaka M., Aoki D.

Journal of Maternal-Fetal and Neonatal Medicine （Journal of Maternal-Fetal and Neonatal Medicine） 35 （ 25 ） 9837 - 9842 2022年12月

ISSN 14767058

Objective: Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery. Methods: We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks). Results: Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (p =.014) was higher and a history of preterm delivery (p =.0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group (p =.0099 and.0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26–13.68, p =.019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88–46.42, p <.0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55–34.86, p =.012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24–20.73, p =.024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11–16.62, p =.035) increased the risk of preterm delivery in the multiple regression models in primiparous women. Conclusion: Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGES Prior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization. The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

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Prognostication of early-onset endometrioid endometrial cancer based on genome-wide DNA methylation profiles

Hirano T., Arai E., Fujimoto M., Nakayama Y., Tian Y., Ito N., Makabe T., Yamagami W., Susumu N., Aoki D., Kanai Y.

Journal of Gynecologic Oncology （Journal of Gynecologic Oncology） 33 （ 6 ） e74 2022年11月

ISSN 20050380

Objective: The aim of this study was to establish criteria that would indicate whether fertility preservation therapy would likely be safe for patients aged 40 years or less with endometrioid endometrial cancer based on their DNA methylation profile. Methods: Forty-nine fresh-frozen tissue samples from patients with endometrial cancer from an initial cohort and 31 formalin-fixed paraffin-embedded tissue samples from a second cohort were subjected to genome-wide DNA methylation analysis using the Infinium MethylationEPIC BeadChip. Results: Epigenomic clustering of early-onset endometrial cancer was correlated with the widely used recurrence risk classification. Genes showing differences in DNA methylation levels between the low-recurrence-risk category and intermediate-and high-risk categories were accumulated in pathways related to fibroblast growth factor and nuclear factor-κB signaling. DNA hypomethylation and overexpression of ZBTB38 were frequently observed in the low-risk category. Eight hundred thirty-one marker CpG probes showed area under the curve values of >0.7 on the receiver operating characteristic curve for discrimination of patients belonging to the low-risk category. By combining marker CpG sites, seven panels for placing patients into the low-risk category with 91.3% or more sensitivity and specificity in both the initial and second cohorts were established. Conclusions: DNA methylation diagnostics criteria using up to 6 of 8 CpG sites for LPP, FOXO1, RNF4, EXOC6B, CCPG1, RREB1 and ZBTB38 may be applicable to recurrence risk estimation for patients aged 40 years or less with endometrial cancer, regardless of tumor cell content, even if formalin-fixed paraffin-embedded biopsy or curettage materials are used.

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卵巣小細胞癌（高カルシウム血症型）の1例

吉村拓馬，西尾浩，家谷佳那，坂井健良，吉浜智子，千代田達幸，山上亘，青木大輔，川井田みほ

関東連合産科婦人科学会誌 59 （ 4 ） 499 - 504 2022年11月

共著

Efficacy and safety of olaparib maintenance monotherapy for Japanese patients with platinum-sensitive relapsed ovarian, fallopian tube, and primary peritoneal cancer

Yoshihama T., Kuroda Y., Chiyoda T., Takahashi M., Yoshimura T., Saotome K., Nanki Y., Sakai K., Kobayashi Y., Yamagami W., Aoki D.

International Journal of Clinical Oncology （International Journal of Clinical Oncology） 27 （ 10 ） 1644 - 1650 2022年10月

ISSN 13419625

Background: Olaparib maintenance therapy for platinum-sensitive relapsed ovarian cancer has been approved in Japan since April 2018. Here, we report the experience administering this therapy in our hospital, with the aim of evaluating efficacy and safety in the Japanese population. Methods: The study included 52 patients with platinum-sensitive relapsed ovarian, fallopian tube, and primary peritoneal cancer. All patients started olaparib at a dose of 300 mg twice daily. Information about treatment efficacy and adverse effects was collected retrospectively from medical records. Results: Median age was 58 years old (range: 33–80), and 82.7% of the patients were diagnosed with high-grade serous carcinoma. Sixteen patients (30.8%) possessed the BRCA1/2 pathogenic variant (15 germline and 1 tissue), 3 (5.8%) possessed variants of unknown significance (2 germline and 1 tissue), 16 (30.8%) possessed wild type, and 17 (32.7%) were not analyzed. Median progression-free survival was 15.3 months (95% CI 9.0–21.6). Patients with BRCA1/2 pathogenic variants showed significantly longer PFS than patients with wild-type BRCA1/2 (p = 0.007). Disease progression caused 34 cases to discontinue olaparib. Eighteen (34.6%) individuals exhibited ≥ grade 3 anemia, although they recovered in response to appropriate management. One patient discontinued olaparib because of prolonged renal dysfunction. Another patient presented with grade 3 fatigue, but recovered after 2 weeks of interruption and continued olaparib treatment. Conclusion: Olaparib maintenance therapy for platinum-sensitive recurrent ovarian cancer in the Japanese population is sufficiently safe and no less effective than reports from previous studies.

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Lenvatinib plus pembrolizumab in Japanese patients with endometrial cancer: Results from Study 309/KEYNOTE-775

Yonemori K., Yunokawa M., Ushijima K., Sakata J., Shikama A., Minobe S., Usami T., Enomoto T., Takehara K., Hasegawa K., Yamagami W., Yamamoto K., Han S., Dutta L., Orlowski R., Miura T., Makker V., Fujiwara K.

Cancer Science （Cancer Science） 113 （ 10 ） 3489 - 3497 2022年10月

ISSN 13479032

Study 309/KEYNOTE-775 is a phase 3 open-label, randomized trial of lenvatinib plus pembrolizumab versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer with progression after platinum-based therapy. Primary endpoints of superiority for lenvatinib plus pembrolizumab were met for progression-free survival (PFS) and overall survival (OS) in all-comers (ie, regardless of mismatch repair [MMR] status) and patients with MMR proficiency (pMMR). We present results for the Japanese subset. Patients were randomized to oral lenvatinib 20 mg/day plus intravenous pembrolizumab 200 mg every 3 weeks (Q3W; up to 35 cycles of pembrolizumab) or TPC (intravenous doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 QW [3 weeks on/1 week off]). Primary endpoints were PFS by blinded independent central review per RECIST version 1.1 and OS. One hundred four patients were randomized in Japan (data cutoff, October 26, 2020; median follow-up, 11.8 [range, 1.1–26.9] months). Hazard ratios (HRs) for PFS with lenvatinib plus pembrolizumab versus TPC were 1.04 (95% CI, 0.63–1.73) in patients with pMMR and 0.81 (0.50–1.31) in all-comers. Hazard ratios for OS were 0.74 (0.41–1.34) with pMMR and 0.59 (0.33–1.04) for all-comers. Adverse events were manageable and led to discontinuation of one/both study drugs in 36.5% of patients in the lenvatinib plus pembrolizumab group versus 7.8% in the TPC group. Similar to the global Study 309/KEYNOTE-775 results, this analysis suggested favorable efficacy and manageable safety with lenvatinib plus pembrolizumab after platinum-based chemotherapy in Japanese patients with advanced endometrial cancer and supports this combination as a new standard of care in this population.

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当院におけるMayer-Rokitansky-Kuester-Hauser症候群17例の診療経験

三宅温子, 小林佑介, 今枝慶蓉, 吉浜智子, 横田めぐみ, 林茂徳, 山上亘, 阪埜浩司, 田中守, 青木大輔

東京産科婦人科学会会誌 71 （ 3 ） 436 - 440 2022年07月

研究論文（学術雑誌）, 共著, 査読有り

TP53 variants in p53 signatures and the clonality of STICs in RRSO samples

Akahane T., Masuda K., Hirasawa A., Kobayashi Y., Ueki A., Kawaida M., Misu K., Nakamura K., Nagai S., Chiyoda T., Yamagami W., Hayashi S., Kataoka F., Banno K., Sugano K., Okita H., Kosaki K., Nishihara H., Aoki D.

Journal of Gynecologic Oncology （Journal of Gynecologic Oncology） 33 （ 4 ） e50 2022年07月

ISSN 20050380

Objective: Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer. Methods: We analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease. Results: TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer. Conclusion: The sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.

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卵巣原発小細胞癌の2例

家谷佳那, 山上亘, 川井田みほ, 吉村拓馬, 北澤晶子, 高橋美央, 坂井健良, 吉浜智子, 辻浩介, 千代田達幸, 冨永英一郎, 青木大輔

日本婦人科病理学会誌 13 （ 1 ） 47 - 54 2022年06月

共著, 責任著者, 査読有り

類内膜癌を癌腫成分に有する卵巣癌肉腫の2例

吉村拓馬, 山上亘, 川井田みほ, 家谷佳那, 北澤晶子, 高橋美央, 坂井健良, 吉浜智子, 野上侑哉, 千代田達幸, 青木大輔

日本婦人科病理学会誌 13 （ 1 ） 33 - 40 2022年06月

研究論文（学術雑誌）, 共著, 責任著者, 査読有り

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