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// Masako Ishikawa 1 , Kentaro Nakayama 1 , Kohei Nakamura 1 , Ruriko Ono 1 , Kaori Sanuki 1 , Hitomi Yamashita 1 , Tomoka Ishibashi 1 , Toshiko Minamoto 1 , Kouji Iida 1 , Sultana Razia 1 , Noriyoshi Ishikawa 2 and Satoru Kyo 1 1 Department of Obstetrics and Gynecology, Shimane University School of Medicine, 6938501 Izumo, Japan 2 Department of Organ Pathology, Shimane University School of Medicine, 6938501 Izumo, Japan Correspondence to: Kentaro Nakayama, email: kn88@med.shimane-u.ac.jp Keywords: ovarian clear cell carcinoma; ovarian endometrioid carcinoma; ARID1A ; POLE ; liquid microdissection Received: September 05, 2017 Accepted: February 13, 2018 Epub: February 22, 2018 Published: March 13, 2018 ABSTRACT Aim: Endometriosis-related ovarian neoplasms (ERONs) have recently attracted considerable attention; however, the prevalence and patterns of ARID1A and POLE mutations in ERONs have not been studied in detail. The aim of this study was to investigate not only the carcinogenesis of ERONs, but also the prognostic significance of several gene mutations in this cohort. We used DNA purified from only tumor epithelial cells, from which fibroblasts were removed, using a specific method we called “liquid microdissection”. Methods: Tissue samples from 22 ovarian carcinomas (13 endometrioid, and nine clear cell) were used. Tumor cells were isolated using a cell sorting system and DNA was purified from tumor epithelial cells. Nucleotide sequencing was conducted to analyze the mutational status of ARID1A, p53, PTEN, POLE, PIK3CA , and KRAS . Results: In ERONs, the frequencies of somatic mutations in ARID1A, p53, POLE, PTEN, PIK3CA , and KRAS were 19/20 (95.0%), 7/19 (36.8%), 9/22 (40.9%), 13/19 (68.4%), 3/19 (15.8%), and 1/9 (11.1%). The frequency of ARID1A mutations was significantly higher than that reported previously. Kaplan-Meier survival analysis revealed that mutations in all genes, including POLE , were not associated with patient prognosis in our Japanese cohort. Conclusions: Our results suggest that the frequency of ARID1A mutations in ERONs may be higher than that previously reported. In addition, the “liquid microdissection” method that we chose for DNA purification could be used to obtain high-quality sequencing results. The findings suggest that ARID1A mutations represent the basis of ERON carcinogenesis; other subsequent gene mutations may result in the progression of carcinogenesis.

The aim of the present study was to determine the prognostic value of the Glasgow prognostic score (GPS) in endometrial carcinoma (EC). Patients with EC who underwent surgery at the Shimane University Hospital between January 1997 and December 2013 were enrolled (n=118). The associations between pretreatment GPS and clinical parameters, including age, histological type, International Federation of Gynecology and Obstetrics stage, tumor grade, carbohydrate antigen 19-9 and carcinoembryonic antigen levels, progression-free survival (PFS), and overall survival (OS), were investigated. Survival analysis was performed with the Kaplan-Meier method, and prognostic factors were evaluated with Cox's proportional hazards regression model. A high pretreatment GPS was associated with advanced clinical stage, histological type and tumor grade (P

Haematogenous metastases of breast cancer tumors has previously been demonstrated to frequently occur at the sites of the lung, bones, liver and brain, however presence in the uterine remains a rare occurrence. Metastatic carcinoma of the uterus usually originates from other genital sites, most frequently from the ovaries. The current review presents the first reported case of lobular breast carcinoma metastasizing to an endometrial polyp, the cervix and a leiomyoma simultaneously. The patient (58 years, female) first presented with abnormal uterine bleeding. Invasive ductal carcinoma had previously been diagnosed in her right breast, with lobular and ductal cancer cells observed to be present in her lymph nodes. A hysteroscopic procedure to examine the postmenopausal bleeding revealed an endometrial polyp, which was subsequently resected. The morphology and immunohistochemical studies confirmed the diagnosis of metastasis of lobular breast carcinoma to an endometrial polyp. An 18F fludeoxyglucose positron emission tomography/computed tomography (PET-CT) scan performed following the diagnosis, revealed a slightly increased uptake in the myoma, which is often observed in benign uterine leiomyoma. The patient then underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy and partial colectomy. Pathology results demonstrated that the uterine leiomyoma and cervix shared the same histopathological features as those presented by the primary lobular breast carcinoma. Although rare, breast tumors may metastasize to an endometrial polyp, cervix and leiomyoma concurrently in patients, therefore physicians may now consider the potential of the diagnosis of metastatic spread to the genital tract, in a patient with abnormal uterine bleeding and a history of lobular breast cancer. Gynecologists planning a laparoscopic hysterectomy for a patient with a history of lobular breast carcinoma may consider abdominal rather than laparoscopic hysterectomy, as lobular carcinoma is difficult to detect. The use of PET-CT may be beneficial for the identification of an unexpected mass.

Ureterolysis is a surgical method with a high level of difficulty, which may be necessary when performing total laparoscopic hysterectomy (TLH) for large cervical myoma, despite the benign nature of this tumor. The aim of the present study was to introduce techniques that are commonly applied in malignant tumor surgery in order to safely perform TLH for large cervical myoma. Between 2014 and 2016, TLH was performed at the Shimane University Hospital (Izumo, Japan) in 153 patients with benign tumors, including 25 cases with a large uterus (uterine weight ≥500 g). The surgical methods applied in 3 of these large uterine cervical myoma cases were investigated in detail, including techniques devised by our department. TLH was performed without enucleating myomectomy in all 3 cases; however, all 3 cases required ureterolysis, transection of the anterior layer of the vesicouterine ligament and isolation of the ureter. In conclusion, although radical laparoscopic hysterectomy is commonly performed for cervical cancer at our department, techniques used for malignant tumor surgery may prove useful for benign cases with a high level of difficulty.

Ovarian low-grade serous carcinoma is thought to begin as a serous cystadenoma or adenofibroma that progresses in a slow stepwise fashion. Among the low-grade serous carcinomas, there is a high frequency of activating mutations in the KRAS or BRAF genes; however, it remains unclear as to how these mutations contribute to tumor progression. This is the first report to track the histopathological progression of serous adenofibroma to low-grade serous carcinoma. Each stage was individually analyzed by pathological and molecular genetic methods to determine what differences occur between the distinct stages of progression.

Objective The aim of the present study was to evaluate the prognostic value of pretreatment plasma dimerized plasmin fragment D (D-dimer) levels in endometrial carcinoma after adjusting for venous thromboembolism (VTE). Study design The relationships between the following clinical parameters from 110 patients were investigated: age, histological type, the International Federation of Gynecology and Obstetrics (FIGO) stage, tumor grade, pretreatment plasma D-dimer level, platelet count, fibrinogen, CA19-9, and CEA levels, progression-free survival (PFS), and overall survival (OS). A survival analysis was performed using the Kaplan–Meier method, and prognostic factors were assessed using Cox's proportional hazards regression model. Results High pretreatment D-dimer levels were detected in 32% of cases. High D-dimer levels correlated with an advanced tumor stage, histological type, and tumor grade ( P =0.001, P =0.021, P =0.044). A multivariate analysis identified high D-dimer levels as an independent prognostic factor for OS ( P =0.013), whereas the histological type, but not D-dimer levels had independent prognostic value for PFS ( P =0.225). Conclusion High pretreatment D-dimer levels have an impact on prognoses independently of VTE, and also have potential as markers to predict surgical outcomes in patients with endometrial carcinoma. Pretreatment D-dimer levels may contribute to the identification of high-risk populations for treatment decisions.