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Gα13, a heterotrimeric G-protein of the Gα12/13 subfamily, is associated with aggressive phenotypes in various human cancers. However, the mechanisms by which Gα13 promotes cancer progression have not been fully elucidated. Here, we demonstrate that the activation of Gα13 induces epithelial-mesenchymal transition in ovarian cancer (OvCa) cells through down-regulation of large tumor suppressor kinase (LATS) 1, a critical component of the Hippo signaling pathway. A synthetic biology approach using a mutant GPCR and chimeric G-protein revealed that Gα13-regulated phosphorylation of LATS1 at serine 909 within its activation loop induced recruitment of the itchy E3 ubiquitin protein ligase to trigger LATS1 degradation. Our findings uncover novel mechanisms through which Gα13 activation induces dysregulation of the Hippo signaling pathway, which leads to aggressive cancer phenotypes, and thereby identify a potential target for preventing the metastatic spread of OvCa.-Yagi, H., Onoyama, I., Asanoma, K., Hori, E., Yasunaga, M., Kodama, K., Kijima, M., Ohgami, T., Kaneki, E., Okugawa, K., Yahata, H., Kato, K. Gα13-mediated LATS1 down-regulation contributes to epithelial-mesenchymal transition in ovarian cancer.

Gastric-type mucinous carcinoma (GAS) is a novel variant of mucinous carcinoma of the uterine cervix. As shown in the original Japanese group description, in recent studies, GAS represents a more aggressive disease than the usual-type endocervical adenocarcinoma (UEA). Detailed clinicopathological features of this variant remain to be elucidated in a larger series of patients.Patients were enrolled by the Gynecologic Cancer Study Group of the Japan Clinical Oncology Group after receiving the approval of each Institutional Review Board. The study population comprised of women with stage I to II endocervical adenocarcinomas who underwent surgery between 2000 and 2009. Representative slides were evaluated by central pathological review (CPR), categorized into either GAS or UEA, and correlated with clinicopathological features and outcome.Among the 393 enrolled patients with endocervical adenocarcinoma, 328 patients met the criteria for CPR and the study eligibility criteria and were included in further analysis. A total of 95 of the 328 tumors were classified as GAS. Compared with UEA, GAS was more significantly associated with bulky mass, deep stromal invasion, lymphovascular space invasion, parametrial invasion, ovarian metastasis, positive ascitic fluid cytology, pelvic lymph node metastasis, and pathological (p) T stage but was not related to the degree of histological differentiation. Disease-free survival (P 0.0001) and overall survival (P 0.0001) were poorer in patients with GAS than in those with UEA.GAS showed aggressive behavior with ominous histopathological predictors as well as decreased survival. GAS is therefore considered a distinct entity that should be distinguished from UEA.UMIN Clinical Trials Registry: UMIN000007987.

To avoid the loss of fertility, chemotherapy should be chosen as an adjuvant treatment after trachelectomy. Our study evaluated the effectiveness and safety of adjuvant chemotherapy after abdominal trachelectomy for cervical cancer. Our institutional review board approved this clinical study, and informed consent was obtained from each patient. We began performing abdominal trachelectomy at our institution in 2005. Deep stromal invasion (more than two-thirds) with lymphovascular space invasion, diffuse cervical invasion, skip lesions in the vagina, and lymphovascular space invasion in the cardinal ligament and vagina were defined as intermediate-risk factors, and parametrial invasion and pelvic lymph node metastasis were defined as high-risk factors. Patients who had intermediate- or high-risk factors received post-trachelectomy adjuvant treatment. The medical records and information of the patients were reviewed retrospectively. Through January 2020, we performed 212 trachelectomies. Among the included patients, 16 and 7 patients with intermediate- and high-risk cancer, respectively, received adjuvant chemotherapy after trachelectomy (2 and 21 patients underwent abdominal modified radical trachelectomy and radical trachelectomy, respectively). Among these patients, only one (4.3%) experienced relapse and subsequent death of the disease after a median postoperative follow-up of 80 months (range 12–146 months). The 5-year survival rate was 95.5%. Chemotherapy-related life-threatening acute adverse events were not observed. Persistent ovarian dysfunction and late adverse events did not occur. One woman achieved three pregnancies, and two infants were delivered. Adjuvant chemotherapy after abdominal trachelectomy could be an alternative treatment option from the aspects of effectiveness, safety, and fertility preservation.

Introduction: Adjuvant therapy is usually recommended for patients with intermediate-risk cervical cancer (deep stromal invasion [DSI], lymphovascular space invasion [LVSI], and bulky tumor) after radical hysterectomy. However, we previously reported that DSI, LVSI, and bulky squamous cell carcinoma (SCC) were not correlated with prognosis in multivariate analysis; therefore, the indications we use for adjuvant therapy include complete stromal invasion, not DSI or LVSI or bulky SCC. The objective of this study was to evaluate the adequacy of our therapeutic strategy for cervical cancer after radical hysterectomy. Methods: We performed 321 type III open radical hysterectomies for cervical cancer between 2001 and 2013. Eighty-two patients with DSI, LVSI, or bulky SCC did not receive adjuvant therapy after radical hysterectomy under informed consent. We retrospectively evaluated the prognosis of these 82 patients. Results: Forty-two patients had >2/3 DSI and 35 patients had 1/3–2/3 DSI. Five patients had LVSI alone. The mean patient age was 43 years (range, 27–72). Six patients (7%) experienced recurrence during a median follow-up period of 84 months (range, 1–206). Two of the 6 patients with recurrence suffered cervical cancer-related deaths, but the remaining 4 cases are alive without evidence of disease after treatment during a follow-up period of 87–165 months. The 5-year disease-free survival rate was 92.6%, and the 5-year overall survival rate was 96.3%. Conclusions: Adjuvant therapy for DSI, LVSI, or bulky SCC after open radical hysterectomy might not be necessary. Further data collection is warranted to determine the standard of care for patients with intermediate-risk cervical ­cancer.

Highlights • This report shows very rare cases of small cell carcinoma of the ovary, hypercalcemic type and pulmonary type. • Their chemo sensitivity is quite different. These two cases followed opposite clinical courses. • The first case (SCOHT) progressed rapidly, and showed resistance to chemotherapy and radiotherapy. • The second case (SCOPT) showed sensitivity to chemotherapy and radiotherapy although recurrence was repeated.

Trachelectomy was developed as a fertility-sparing surgery for early-stage cervical cancer in patients of childbearing age. The purpose of this study is to evaluate oncologic and obstetric outcomes and complications after abdominal trachelectomy. We began to perform abdominal trachelectomy in 2005. Our institutional review board approved this clinical study, and fully informed consent was obtained from each patient. The medical records of patients who underwent trachelectomy were retrospectively reviewed. We performed 151 abdominal trachelectomies (89 radical trachelectomies, 48 modified radical trachelectomies, and 14 simple trachelectomies). The median age of the patients was 33 years, and the median postoperative follow-up period was 61 months. Although one patient experienced recurrence at the preserved cervix, none died after treatment. A total of 61 patients attempted to conceive after trachelectomy, and 21 pregnancies were achieved in 15 women. Hence, the pregnancy rate among patients who attempted to conceive was 25%. Fifteen babies were delivered by cesarean section between gestational weeks 23 and 37. Six babies were delivered at term. Six cases of preterm premature rupture of the membranes occurred. Varices appeared around the uterovaginal anastomotic site in five patients. Our data indicate that the oncologic outcome was excellent but infertility treatment was necessary to achieve the majority of conceptions. Additionally, preterm premature rupture of the membranes and premature delivery were frequently observed. An improved pregnancy rate and prevention of complications during pregnancy are issues that should be addressed in future studies.

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Aim To evaluate how the desire to have children and engage in sexual activity change after trachelectomy in Japanese women with early-stage cervical cancer who strongly desired to have children before surgery. Methods Desire to have children, coital pain, fear of sexual intercourse, sexual activity frequency and libido were assessed in cervical cancer patients who received follow-up after trachelectomy. An anonymous questionnaire survey was conducted via informed consent. Results Of the 151 patients who underwent trachelectomy at Kyushu University Hospital between 2005 and 2015, 46 patients were evaluated; the response rate was 30%. The desire to have children disappeared in 13 of 46 (28%) patients, and 14 (30%) patients experienced increased coital pain. Moreover, 19 (41%) patients experienced fear of sexual intercourse, and sexual frequency decreased in 24 (52%) patients. Conclusion Trachelectomy is an important fertility-sparing surgical method; however, this study revealed loss of the desire to have children and/or to engage in sexual activity in some patients after surgery. Counseling about these issues is important and should be addressed.

BHLHE40 and BHLHE41 (BHLHE40/41) are basic helix-loop-helix type transcription factors involved in multiple cell activities including epithelial-to-mesenchymal transition (EMT). However, the expression mechanism of BHLHE40/41 in EMT remains unclear. In the present study, we showed that the expression levels of BHLHE40/41 were negatively correlated with those of the microRNA (MIR) 130 family in endometrial cancer (EC) specimens. Our in vitro assays indicated that the expression of BHLHE40/41 was suppressed directly by the MIR130 family in a 3'-untranslated region-mediated manner. In EC cells, the MIR130 family promoted EMT and tumor cell invasion by suppressing the expression of BHLHE40/41. We identified the critical promoter region of the MIR301B-MIR130B cluster for its basal transcription by the transcription factor, SP1. We also found that BHLHE40/41 suppressed the expression of MIR301B and MIR130B, and we identified a binding site in the promoter region for BHLHE40/41. This study is the first to report that BHLHE40/41 and the MIR301B-MIR130B cluster suppressed each other to regulate EMT and invasion of EC cells. We propose that BHLHE40/41 and the MIR130 family are excellent markers to predict the progression of EC cases, and that molecular therapy targeting the MIR130 family-BHLHE40/41 axis may effectively control EC extension.

Objective: For oncologic safety, vaginal radical trachelectomy is generally performed only in patients with cervical cancers smaller than 2 cm. However, because inclusion criteria for abdominal trachelectomy are controversial, we evaluated the safety of abdominal trachelectomy for cervical cancers ≥2 cm. / Methods: We began performing abdominal trachelectomies at our institution in 2005, primarily for squamous cell carcinoma ≤3 cm or adenocarcinoma/adenosquamous carcinoma ≤2 cm. If a positive sentinel lymph node or cervical margin was diagnosed intraoperatively by frozen section, the trachelectomy was converted to a hysterectomy. Medical records of these patients were reviewed retrospectively. Patients who had undergone simple abdominal trachelectomy were excluded from this study. / Results: We attempted trachelectomy in 212 patients. Among the 135 patients with tumors

Aim: This study aimed to clarify the genetic and epigenetic features of recurrent hydatidiform mole (RHM) in Japanese patients. Methods: Four Japanese isolated RHM cases were analyzed using whole-exome sequencing. Villi from RHMs were collected by laser microdissection for genotyping and DNA methylation assay of differentially methylated regions (DMRs). Single nucleotide polymorphisms of PEG3 and H19 DMRs were used to confirm the parental origin of the variants. Results: A novel homozygous nonsense mutation in NLRP7 (c.584G>A; p.W195X) was identified in 1 patient. Genotyping of one of her molar tissue revealed that it was biparental but not androgenetic in origin. Despite the fact that the RHM is biparental, maternally methylated DMRs of PEG3, SNRPN and PEG10 showed complete loss of DNA methylation. A paternally methylated DMR of H19 retained normal methylation. Conclusions: This is the first Japanese case of RHM with a novel homozygous nonsense NLRP7 mutation and a specific loss of maternal DNA methylation of DMRs. Notably, the mutation was identified in an isolated case of an ethnic background that has not previously been studied in this context. Our data underscore the involvement of NLRP7 in RHM pathophysiology and confirm that DNA methylation of specific regions is critical.

Only a few reports of pelvic abscess as a late complication of trachelectomy have been published to date. To evaluate the cases of pelvic abscess as a late complication of abdominal trachelectomy for cervical cancer.In June 2005, we began a clinical trial of abdominal trachelectomy at our institution. Written informed consent was obtained from all patients. We retrospectively reviewed the medical records of patients who underwent trachelectomy and extracted the data of patients who experienced pelvic abscess as a late complication.From June 2005 to September 2017, we performed 181 trachelectomies at our institution. In total, 15 pelvic abscesses occurred in 12 of these patients more than 1 month after trachelectomy. The median postoperative period before the onset of pelvic abscess was 51 months (range, 1-104 months). Among the 15 cases, abscess formed in the uterine adnexa in 12, in a pelvic lymphocyst in two, and in the uterus in one. Abscess drainage was performed in six cases. Three patients underwent laparotomy with salpingo-oophorectomy.It is possible that not only surgical removal of the uterine cervix but also the use of nonabsorbable suture in cervical cerclage and placement of an intrauterine device triggered post-trachelectomy infection. Pelvic abscess can occur as a late complication of abdominal trachelectomy.

Background and Objectives: Trachelectomy, a fertility-sparing surgery for early-stage cervical cancer, can be performed only when there is no extrauterine extension present. Therefore, identifying the sentinel lymph nodes (SLNs) and using them to obtain an intraoperative pathologic diagnosis can provide information on the feasibility and safety of trachelectomy. Our aim was to assess the value of an intraoperative SLN diagnosis. Methods: We retrospectively analyzed the accuracy of intraoperative imprint cytology and frozen-section examination in 201 patients at our institution in whom trachelectomy was planned. Results: All patients could be evaluated for SLNs; a total of 610 SLNs were analyzed. Although the specificity of both imprint cytology and frozen-section examination was 100.0%, the sensitivity was only 58.6 and 65.5%, respectively. The diagnostic sensitivity was higher in 2-mm slices along the short axis than on bisection along the longitudinal axis. Imprint cytology correctly diagnosed 2 patients who had false-negative results on frozen section. The nature of the metastatic foci that caused an intraoperative false-negative diagnosis was either micrometastasis or isolated tumor cells. Conclusions: The accuracy of intraoperative SLN diagnosis requires improvement, especially when small metastatic foci are present.

Müllerian mucinous borderline tumors (MMBTs) usually arise from the ovary. The present report is the first case of primary uterine MMBTs associated with adenomyosis. A 51-year-old woman was referred to our hospital for a complex cystic and solid 4×3 cm right adnexal mass. She had a history of a left ovarian endometriotic cyst and had undergone a left oophorectomy 2 yr prior. A laparotomy was performed, and the tumor was found to be originating in the posterior wall of the uterus. She underwent a total abdominal hysterectomy, right salpingo-oophorectomy, and left salpingectomy. Microscopically, the solid portion of the tumor contained papillary proliferations of glands, which were covered by a mucinous epithelium with mild to moderate nuclear atypia, accompanied by stromal infiltration of inflammatory cells. Islands of adenomyosis were also observed around the cyst. These pathologic findings were similar to the features of ovarian MMBT. We diagnosed this tumor as a uterine MMBT, probably arising from adenomyosis.

Genomic imprinting is a form of epigenetic regulation that results in the expression of either the maternally or paternally inherited allele of a subset of genes (Ramowitz and Bartolomei 2011). This imprinted expression of transcripts is crucial for normal mammalian development. In humans, loss-of-imprinting of specific loci results in a number of diseases exemplified by the reciprocal growth phenotypes of the Beckwith-Wiedemann and Silver-Russell syndromes, and the behavioral disorders Angelman and Prader-Willi syndromes (Kagami et al. 2008; Buiting 2010; Choufani et al. 2010; Eggermann 2010; Kelsey 2010; Mackay and Temple 2010). In addition, aberrant imprinting also contributes to multigenic disorders associated with various complex traits and cancer (Kong et al. 2009; Monk 2010). Imprinted loci contain differentially methylated regions (DMRs) where cytosine methylation marks one of the parental alleles, providing cis-acting regulatory elements that influence the allelic expression of surrounding genes. Some DMRs acquire their allelic methylation during gametogenesis, when the two parental genomes are separated, resulting from the cooperation of the de novo methyltransferase DNMT3A and its cofactor DNMT3L (Bourc'his et al. 2001; Hata et al. 2002). These primary, or germline imprinted DMRs are stably maintained throughout somatic development, surviving the epigenetic reprogramming at the oocyte-to-embryo transition (Smallwood et al. 2011; Smith et al. 2012). To confirm that an imprinted DMR functions as an imprinting control region (ICR), disruption of the imprinted expression upon genetic deletion of that DMR, either through experimental targeting in mouse or that which occurs spontaneously in humans, is required. A subset of DMRs, known as secondary DMRs, acquire methylation during development and are regulated by nearby germline DMRs in a hierarchical fashion (Coombes et al. 2003; Lopes et al. 2003; Kagami et al. 2010). With the advent of large-scale, base-resolution methylation technologies, it is now possible to discriminate allelic methylation dictated by sequence variants from imprinted methylation. Yet our knowledge of the total number of imprinted DMRs in humans, and their developmental dynamics, remains incomplete, hampered by genetic heterogeneity of human samples. Here we present high-resolution mapping of human imprinted methylation. We performed whole-genome-wide bisulfite sequencing (WGBS) on leukocyte-, brain-, liver-, and placenta-derived DNA samples to identify partially methylated regions common to all tissues consistent with imprinted DMRs. We subsequently confirmed the partial methylated states in tissues using high-density methylation microarrays. The parental origin of methylation was determined by comparing microarray data for DNA samples from reciprocal genome-wide uniparental disomy (UPD) samples, in which all chromosomes are inherited from one parent (Lapunzina and Monk 2011), and androgenetic hydatidiform moles, which are created by the fertilization of an oocyte lacking a nucleus by a sperm that endoreduplicates. The use of uniparental disomies and hydatidiform moles meant that our analyses were not subjected to genotype influences, enabling us to characterize all known imprinted DMRs at base-pair resolution and to identify 21 imprinted domains, which we show are absent in mice. Lastly, we extended our analyses to determine the methylation profiles of all imprinted DMRs in sperm, stem cells derived from parthenogenetically activated metaphase-2 oocyte blastocytes (phES) (Mai et al. 2007; Harness et al. 2011), and stem cells (hES) generated from both six-cell blastomeres and the inner cell mass of blastocysts, delineating the extent of embryonic reprogramming that occurs at these loci during human development.

Metastasis to the mandibular condyle is rare, and such lesions should be identified by both clinical and pathological examinations. We experienced a case of adenocarcinoma occurring in the right mandibular condyle. A 65-year-old female with uterine cervical cancer showed condylar dysfunction. Imaging examinations revealed a tumor with bone destruction and a rapidly progressive course, while pathological examinations suggested metastasis originating from another site. Based on the clinical and pathological findings, the patient was diagnosed with condylar metastasis derived from the uterine cervix, in addition to a recurrence of uterine cervical cancer.

Aim To investigate the surgical outcome of FIGO stage IA1 cervical adenocarcinoma. Methods Between 2005 and 2011, 12 patients from Kyushu University Hospital had cervical adenocarcinoma, with a tumor depth of less than 3 mm and a horizontal width of less than 7 mm (FIGO stage IA1), diagnosed by cervical conization. All patients underwent simple hysterectomy or simple trachelectomy with pelvic lymphadenectomy. Results The mean patient age was 34 years (range, 26-70 years). The median follow-up period was 70.5 months (range, 26-99 months). No pelvic lymph-node metastasis was seen, and no patient experienced disease recurrence. Conclusion Early invasive cervical adenocarcinoma with a depth of invasion of 3 mm or less and a horizontal spread of 7 mm or less has little potential for nodal metastasis or recurrence. Therefore, simple hysterectomy or trachelectomy, without lymphadenectomy, might be an alternative treatment option for stage IA1 cervical adenocarcinoma.

In the present study, we evaluated the incidence of postmolar gestational trophoblastic disease (GTD) in molar pregnancy. We also validated the macroscopic diagnosis based on the Japan Society of Obstetrics and Gynecology (JSOG) classification. A total of 297 samples of hydropic villi were classified according to DNA polymorphisms as androgenetic moles, dispermic triploids, or biparental diploids (hydropic abortion), clinically corresponding to complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), and hydropic abortion, respectively. These samples were also classified morphologically based on the JSOG classification. A follow-up study was performed to investigate the incidence of postmolar GTD. A subset of 267 samples eligible for testing were analyzed and diagnosed as androgenetic moles (232 cases), dispermic triploids (20 cases), and biparental diploids (15 cases). Most of the macroscopically diagnosed CHM cases were genetically androgenetic in origin. The PHM cases consisted of 30 androgenetic moles and 12 dispermic triploids. We reviewed the outcomes of 200 patients (178 cases of androgenetic mole, 13 cases of dispermic triploids, and nine cases of biparental diploids). Twenty-eight cases (16%) of androgenetic moles developed postmolar GTD. None of the patients with dispermic triploids developed postmolar GTD. Among the 28 patients who developed postmolar GTD, the shortest diameter of the largest hydropic villi was significantly longer than that of patients not developing postmolar GTD. None of the patients with androgenetic moles who had hydropic villi

Aims: Squamous cell carcinoma (SCC) is the most common form of malignant transformation in mature cystic teratoma (MCT) of the ovary. Some investigators have suggested the possibility of origin from columnar epithelium. The aim of this study was to analyse such tumours immunohistochemically to elucidate their histogenesis. Methods and results: The expression of cytokeratin (CK) 10 and CK18 was examined in 21 samples of SCC arising in MCT. The expression of CK10 and CK18 was also assessed in SCCs arising in different organs (skin, vulva, lung and uterine cervix) for the purpose of comparison. SCC in MCT expressed CK10 in 7/21 cases [33.3%, 95% confidence interval (CI) 0.12–0.53] and CK18 in 14/21 cases (66.7%, 95% CI 0.46–0.87). SCC in MCT expressed CK10 less frequently, but CK18 more frequently, as is the case in SCCs of the uterine cervix (CK10, 20%; CK18, 70%) and the lung (CK10, 5%; CK18, 90%), both of which are derived from columnar epithelium by squamous metaplasia. Conclusions: SCC in MCT may be derived from metaplastic squamous epithelium.

Background. Cases of malignant ovarian tumor composed of mullerian-type epithelial tumor and malignant germ cell tumor are extremely rare. Case. We herein report the case of a 34-year-old woman with an ovarian tumor which was composed of endometrioid adenocarcinoma (EAC), clear cell adenocarcinoma (CCC), squamous cell carcinoma, yolk sac tumor (YST) and immature teratoma with prominent neuroectodermal and rhabdomyosarcomatous differentiation. Even after systemic chemotherapy, this intriguing tumor recurred again and again, which is in contrast to pure germ cell tumor which is known to be sensitive to chemotherapy. Conclusion. No previous cases with an identical composition have been found in the literature. Correct diagnosis of this complex and aggressive tumor is paramount.

Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced cervical cancer. The purpose of the study was to compare the outcomes of triweekly cisplatin plus 5-fluorouracil and weekly cisplatin regimens.We retrospectively reviewed data from 91 patients with stage IB1-IVA cervical cancer.Out of 91 patients, 48 received triweekly CCRT and 43 received weekly CCRT. For triweekly CCRT, patients received a median of two chemotherapy cycles and median total doses of cisplatin and 5-fluorouracil were 210 mg/body and 8,525 mg/body, respectively. For weekly CCRT, patients received a median of five chemotherapy cycles and the median total dose of cisplatin was 252 mg/body. No statistically significant differences in overall survival or progression-free survival were noted between the two groups.Both triweekly CCRT and weekly CCRT appear to have similar efficacy for cervical cancer patients, but the toxicities were better tolerable in weekly CCRT.

Uterine myxoid leiomyosarcoma (MLMS) is an extremely rare variant of uterine leiomyosarcoma; only 56 cases were reported from 1982 to 2013. Uterine MLMS is characterized by a myxoid appearance and highly malignant behavior. We herein report a case involving a 65-year-old woman with uterine MLMS with a large tumor embolism that reached the right atrium. A total abdominal hysterectomy, bilateral salpingooophorectomy, and tumor embolism resection with the use of a heart-lung machine were performed. Epirubicin-ifosfamide chemotherapy in the adjuvant setting led to reductions in both the tumor emboli and peritoneal dissemination. The patient retained a good quality of life for 10 months after the initial surgery. She then developed progressive disease despite treatment with pazopanib. She died of her disease 14 months after the initial surgery. Although complete surgical resection of the tumor is desirable, tumor reduction surgery followed by adjuvant chemotherapy might help to retain a good quality of life. This is the first reported case of a primary uterine MLMS with tumor emboli.

The objective of our study was to determine the usefulness of recognizing the continuity of the gonadal veins to the pelvic mass to differentiate ovarian versus uterine origin on MDCT in females with a large pelvic mass.Two radiologists interpreted the MDCT images obtained on a monitor, using paging methods, in 86 female patients with a large pelvic mass (8 cm) and 40 patients without an abdominopelvic mass as control subjects. The following issues were recorded using a 5-point scale: visualization of gonadal veins and origin determination based on anatomic continuity. Receiver operating characteristic (ROC) curve analysis was performed, and the interobserver differences were checked with kappa statistics. The maximum diameters of the gonadal veins were also measured. With consensus interpretations, the sensitivity, specificity, and accuracy of ovarian origin determination were calculated.Gonadal veins were shown in more than 70% of the subjects in both the control group and the patients with a mass (hereafter referred to as the "mass group"). There was no significant difference in the diameter of the gonadal veins between the control and mass groups and between patients with an ovarian mass and those with a uterine mass. The values for the area under the ROC curve (A(z)) of the two observers for ovarian origin determination were 0.90 and 0.92. The kappa value was 0.48. The sensitivity, specificity, and accuracy were 83.3%, 87.5%, and 84.9%, respectively.Gonadal veins can be shown on MDCT with high consistency; MDCT provides useful information for determining the origin of relatively large pelvic tumors arising in females.

Synchronous tumors of the ovary and endometrium are a well-known phenomenon. There are histological criteria for defining double primary tumors or metastasis from one organ to another, but in some cases a precise diagnosis is difficult. In this study we reviewed 17 cases of synchronous ovarian and endometrial adenocarcinoma by previously reported histological criteria and performed a microsatellite analysis, combined with X-linked clonality analysis. We also analyzed 8 cases of endometrial adenocarcinoma with pelvic lymph node metastasis as a control. Five dinucleotide microsatellite markers were selected, and microsatellite analysis was performed by a high-resolution method using fluorescence-labeled polymerase chain reaction and laser scanning. In synchronous tumors, 11 ovarian carcinomas (65%) and 10 endometrial carcinomas (59%)demonstrated microsatellite instability (MSI). In total, 13 of the 17 patients demonstrated MSI in the ovarian tumor, the endometrial tumor, or both. Four cases of endometrial carcinoma with pelvic lymph nodes metastases displayed MSI, and MSI findings of the endometrial tumor and lymph node metastasis were same in all cases. Based on these findings, we considered that similar MSI findings indicate metastatic tumors. According to the MSI findings, 13 of the 17 patients (76%) had single or double clonal tumors, 11 (67%) with double primary tumors and 2 (13%) with metastatic tumors. Using X-linked clonality analysis, 3 patients were diagnosed with double primary tumors. The molecular diagnosis corresponded with the histological criteria in all but 1 case. In conclusion, using both MSI and X-linked clonality analysis, most patients (82%) could be diagnosed as having single or double clonal tumors. The histological criteria are accurate and useful in most cases; however, in some cases where the relationship between the 2 tumors is difficult to determine, high-resolution MSI analysis may be helpful.

We experienced 5 cases of clear cell adenocarcinoma (CCAC) of the cervix in the 10-year period from 2003 to 2012. Because a specimen from one of the cases was poorly preserved, we analyzed cytological features of the 4 remaining cases. Characteristic large, pale-staining atypical cells with prominent, round nuclei were seen in all cases. Additionally, a hobnail appearance and basement membrane-like substance were detected in 3 cases, and a mirror ball cluster-like morphology was found in 1 case. Cervical CCAC has been reported to be difficult to diagnose by cytology; however, we were able to diagnose these 4 cases by recognizing several characteristic cytological features.

This chapter discusses the role of immunohistochemical (IHC) expression of Ki-67 in ovarian carcinoma. The optimal method of IHC for Ki-67 antigen, using formalin-fixed and paraffin-embedded tissue specimen, is described in the chapter. The value of the Ki-67 expression, in patients with ovarian carcinoma (OC), using the optimal method, is also discussed in this chapter. The optimal method of Ki-67 immunostaining, by using tonsilar tissue, as a positive control tissue specimen is set-up. Two different methods of antigen retrieval, such as enzyme predigestion or heat treatment, are tested. The optimal method evaluates the Ki-67 expression of the tumor samples taken from 29 patients, with serous papillary adenocarcinoma, treated by debulking surgery and platinum-based chemotherapy, and the results are compared with prognosis. The expression of p16, cyclin D1, and pRb, which are the G1-S phase cell cycle checkpoint proteins, to clarify the co-regulation of them is described in the chapter. The expression of the proteins in the tumor samples, taken from 20 patients, with clear cell adenocarcinoma, to compare with that of serous phenotype, is also discussed in the chapter.

We recently treated a 21-year-old woman with leiomyomas arising from the bilateral ovaries, a very rare condition. On magnetic resonance imaging, more than half of the left adnexal mass showed low signal intensity on T2-weighted images and good enhancement by gadolinium-DTPA, and the remaining part showed high signal intensity on T2-weighted images and no enhancement. The right adnexal mass showed homogeneously low signal intensity on T2-weighted images, so the lesions initially were diagnosed as ovarian fibromas or as the-comas with a certain degree of degeneration. Pathologic examination of the excised tumors proved that they were bilateral ovarian leiomyomas; in addition, the tumor from the left side showed hemorrhagic and myxoid changes with torsion of 180 degrees.

Aim: We previously reported that gastric-type adenocarcinoma (GAS), a subtype of mucinous adenocarcinoma of the cervix, is more significantly associated with histopathological predictors of poor outcomes as well as with poorer survival outcomes than is usual-type endocervical adenocarcinoma (UEA). It is therefore clinically important to distinguish GAS from UEA (ASCO 2014). However, the cause of its aggressive nature remains unknown. We therefore studied the aggressive nature of GAS in patients with disease recurrence. Methods: Patients were enrolled at the Gynecologic Cancer Study Group of the JCOG after receiving approval from an internal review board. Among 393 women with adenocarcinoma of the cervix who were enrolled, 328 with mucinous adenocarcinoma of the cervix who met the central pathological review (CPR) and eligibility criteria were included in analysis. GAS was diagnosed in 95 (28.9%) of the 328 patients. Sites of recurrence of GAS and UEA and the response to treatment (chemotherapy, radiotherapy) given after recurrence were analyzed using statistical techniques. Treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). Results: Overall, recurrence occurred in 72 of the 328 patients: 38 (40%) of 95 patients with GAS and 34 (14.6%) of 233 patients with UEA. Recurrence was clearly more common among patients with GAS (p = 0.0023). In the GAS group, the sites of recurrence were local in 15 patients, distant in 15, and local plus distant in 8. In the UEA group, the sites of recurrence were local in 19 patients, distant in 11, and local plus distant in 4, with no significant difference between the groups. After recurrence, chemotherapy was given to 19 patients with GAS, with a response rate of 36.8% (7/19), and 25 patients with UEA, with a response rate of 32.0% (8/25). The difference in response rates was not significant. Radiotherapy was given to 12 patients with GAS, with a response rate of 50.0% (6/12), and 11 patients with UEA, with a response rate of 81.8% (9/11, p Conclusions: Sites of recurrence sites and the response to chemotherapy did not differ significantly between patients with GAS and those with UEA who had recurrence. Resistance to radiotherapy may reflect the aggressive nature of GAS. Disclosure: All authors have declared no conflicts of interest.