Characteristic of Endometrial Stromal Sarcoma by Algorithm of Potential Biomarkers for Uterine Mesenchymal Tumor.

The benign tumor uterine leiomyoma (UL) develops from the smooth muscle tissue that constitutes the uterus, whereas malignant tumor uterine sarcoma develops from either the smooth muscle tissue or stroma and is different from UL and endometrial cancer. Uterine sarcoma is broadly classified into three types: uterine leiomyosarcoma, endometrial stromal sarcoma (ESS), and carcinosarcoma. Although uterine leiomyosarcoma and ESS are both classified as uterine sarcoma, they significantly differ in terms of their sites of occurrence, symptoms, and treatment methods. Uterine leiomyosarcoma develops from the muscle tissue constituting the wall of the uterus and accounts for approximately 70% of all uterine sarcoma cases. In contrast, ESS develops from the stromal tissue beneath the endometrium and accounts for approximately 25% of all uterine sarcoma cases. ESS is classified as either low grade (LG) or high grade (HG). This case report aimed to highlight the importance of histopathologic examinations based on surgical specimens. Herein, we reported the case of a 45-year-old woman suspected of having submucosal leiomyoma of the uterus based on imaging results. Transvaginal ultrasonography and endometrial biopsy or partial dilation and curettage were performed. Contrast-enhanced magnetic resonance imaging (MRI) revealed a 32-mm mass projecting from the posterior wall of the uterus into the uterine cavity. T2-weighted imaging revealed a low signal within the mass; thus, submucosal UL was suspected. Histopathologic examination of surgical specimens obtained from a patient suspected of having submucosal UL after contrast-enhanced MRI indicated that the patient had ESS. Despite the remarkable advancements in medical imaging technology, the accuracy of contrast-enhanced MRI for detecting uterine mesenchymal tumors is limited. Therefore, histopathologic diagnosis based on surgical specimens should be performed when medical grounds for diagnosing a benign tumor on contrast-enhanced MRI are lacking.

Dynamic host immunity and PD-L1/PD-1 blockade efficacy: developments after "IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer".

In the article titled "IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer" in 2015, we showed that PD-L1 expression is induced by IFN-γ from lymphocytes in the tumour microenvironment. This article proposed that PD-L1 expression in cancer cells is not stable but varies among cases, or even within a case, which is influenced by the stromal infiltration of cytotoxic lymphocytes. Immune-checkpoint inhibitors, especially anti-PD-1/PD-L1 therapies, are now widely used to treat various types of cancer. Predictive biomarkers for the efficacy of immune-checkpoint inhibitors include PD-L1 expression, MSI/mismatch repair deficiency and high tumour mutation burden. However, clinical trials have proven that their use in ovarian cancer is still challenging. Reliable biomarkers and new treatment strategies may be sought by elucidating the complex immune microenvironment of ovarian cancer. Although the interaction between cytotoxic lymphocytes and PD-1/PD-L1 on tumour cells is at the centre of therapeutic targets, other immune checkpoints and various immunosuppressive cells also play important roles in ovarian cancer. Targeting these role players in combination with PD-1/PD-L1 blockade may be a promising therapeutic strategy.

Immunosuppressive tumor microenvironment in uterine serous carcinoma via CCL7 signal with myeloid-derived suppressor cells.

Serous carcinoma of the uterus (USC) is a pathological subtype of high-grade endometrial cancers, with no effective treatment for advanced cases. Since such refractory tumors frequently harbor antitumor immune tolerance, many immunotherapies have been investigated for various malignant tumors using immuno-competent animal models mimicking their local immunities. In this study, we established an orthotopic mouse model of high-grade endometrial cancer and evaluated the local tumor immunity to explore the efficacy of immunotherapies against USC. A multivariate analysis of 62 human USC cases revealed that the tumor-infiltrating cell status, few CD8+ cells and abundant myeloid-derived suppressor cells (MDSCs), was an independent prognostic factor (P < 0.005). A murine endometrial cancer cell (mECC) was obtained from C57BL/6 mice via endometrium-specific deletion of Pten and Tp53, and another high-grade cell (HPmECC) was established by further overexpressing Myc in mECCs. HPmECCs exhibited higher capacities of migration and anchorage-independent proliferation than mECCs (P < 0.01, P < 0.0001), and when both types of cells were inoculated into the uterus of C57BL/6 mice, the prognosis of mice bearing HPmECC-derived tumors was significantly poorer (P < 0.001). Histopathological analysis of HPmECC orthotopic tumors showed serous carcinoma-like features with prominent tumor infiltration of MDSCs (P < 0.05), and anti-Gr-1 antibody treatment significantly prolonged the prognosis of HPmECC-derived tumor-bearing mice (P < 0.05). High CCL7 expression was observed in human USC and HPmECC, and MDSCs migration was promoted in a CCL7 concentration-dependent manner. These results indicate that antitumor immunity is suppressed in USC due to increased number of tumor-infiltrating MDSCs via CCL signal.

Tertiary lymphoid structures are associated with favorable survival outcomes in patients with endometrial cancer.

Immunotherapy has experienced remarkable growth recently. Tertiary lymphoid structures (TLSs) and B cells may play a key role in the immune response and have a survival benefit in some solid tumors, but there have been no reports about their role in endometrial cancer (EC). We investigated the clinicopathological and pathobiological characteristics of the tumor microenvironment (TME) in EC. Patients with EC at Kyoto University Hospital during 2006-2011 were retrospectively included. In 104 patients with EC who met study inclusion criteria, 81 (77.9%) had TLSs, which consisted of areas rich in CD20+ B cells, CD8+ T cells, CD4+ T cells, and CD38+ plasma cells. The absence of TLS was independently associated with tumor progression (HR, 0.154; 95% CI, 0.044-0.536; P = 0.003). Patients with TLSs that included CD23+ germinal centers had better PFS. All tumor infiltrating lymphocytes were counted in the intratumor site. The number of CD20+ B cells was significantly larger in patients with TLSs than in those without TLS (P < 0.001). CD20+ B cells numbers were positively correlated with other TLSs. The larger number of CD20+ B cell was associated with better PFS (P = 0.015). TLSs and B cell infiltration into tumors are associated with favorable survival outcomes in patients with EC. They may represent an active immune reaction of the TME in endometrial cancer.

Visceral-to-subcutaneous fat ratio is a possible prognostic factor for type 1 endometrial cancer.

BACKGROUND: Associations have been observed between obesity defined by the body mass index (BMI) and the incidence of endometrial cancer. However, the impact of obesity on the prognosis of endometrial cancer is not yet clear. Recently, visceral fat has been considered to have a greater impact on malignant disease in obese patients than subcutaneous fat. In this study, we investigated the association between prognostic factors of type 1 and type 2 endometrial cancer and obesity parameters. METHODS: The impacts of clinical factors on the progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively in 145 primary endometrial cancer patients. The factors included age, BMI, pathological findings, Federation of Gynecology and Obstetrics (FIGO) stage, status of lymph node metastasis, and the amounts of visceral and subcutaneous fat obtained from computed tomography (CT) data. RESULTS: Only the visceral-to-subcutaneous fat ratio (V/S ratio) (cutoff value 0.5) corresponded to a significant difference in OS and PFS in type 1 endometrial cancer (p = 0.0080, p = 0.0053) according to the results of log-rank tests of Kaplan-Meier curves. The COX regression univariate analysis revealed that only the V/S ratio was a significant prognostic factor for PFS, but not OS (p = 0.033 and p = 0.270, respectively). CONCLUSION: A V/S ratio > 0.5 is a possible factor for poor prognosis in type 1 endometrial cancer. Further research is needed to investigate the preventive and therapeutic effects of reducing visceral fat on the prognosis of this type of cancer.

Oncological Properties of Intravenous Leiomyomatosis: Involvement of Mesenchymal Tumor Stem-Like Cells.

Uterine leiomyoma, also known as fibroids, is the most common benign neoplasm of the female genital tract. Leiomyoma is the most common uterine tumor. The leiomyoma subtypes account for approximately 10% of leiomyomas. Intravenous leiomyomatosis, a uterine leiomyoma subtype, is an intravascular growth of benign smooth muscle cells, occasionally with pelvic or extrapelvic extension. Uterine leiomyosarcoma, a malignant tumor, tends to metastasize hematogenously, and distant metastasis to the lungs and liver is common. Therefore, the oncological properties of this intravenous leiomyomatosis resemble those of the malignant tumor uterine leiomyosarcoma. Cancer stem cells migrate to distant organs via intravascular infiltration, leading to micrometastases. We examined the oncological properties of intravenous leiomyomatosis using molecular pathological techniques on tissue excised from patients with uterine leiomyoma. CD44-positive mesenchymal tumor stem-like cells were detected in both patients with intravenous leiomyomatosis and uterine leiomyosarcoma. The oncological properties of intravenous leiomyomatosis were found to be similar to those of uterine leiomyosarcoma. However, in intravenous leiomyomatosis, cyclin E and Ki-67-positive cells were rare and no pathological findings suspecting malignancy were observed. It is expected that establishing a treatment method targeting cancer stem cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

PDK2 leads to cisplatin resistance through suppression of mitochondrial function in ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (CCC) exhibits an association with endometriosis, resistance to oxidative stress, and poor prognosis owing to its resistance to conventional platinum-based chemotherapy. A greater understanding of the molecular characteristics and pathogenesis of ovarian cancer subtypes may facilitate the development of targeted therapeutic strategies, although the mechanism of drug resistance in ovarian CCC has yet to be determined. In this study, we assessed exome sequencing data to identify new therapeutic targets of mitochondrial function in ovarian CCC because of the central role of mitochondria in redox homeostasis. Copy number analyses revealed that chromosome 17q21-24 (chr.17q21-24) amplification was associated with recurrence in ovarian CCC. Cell viability assays identified an association between cisplatin resistance and chr.17q21-24 amplification, and mitochondrion-related genes were enriched in patients with chr.17q21-24 amplification. Patients with high expression of pyruvate dehydrogenase kinase 2 (PDK2) had a worse prognosis than those with low PDK2 expression. Furthermore, inhibition of PDK2 synergistically enhanced cisplatin sensitivity by activating the electron transport chain and by increasing the production of mitochondrial reactive oxygen species. Mouse xenograft models showed that inhibition of PDK2 with cisplatin inhibited tumor growth. This evidence suggests that targeting mitochondrial metabolism and redox homeostasis is an attractive therapeutic strategy for improving drug sensitivity in ovarian CCC.

Potential Novel Ovarian Cancer Treatment Targeting Myeloid-Derived Suppressor Cells.

Diagnosis by biopsy is difficult in the ovary since it is located deep in the abdomen. As a result, ovarian cancer is mostly found insidiously during exploratory laparotomy. Consequently, the early diagnosis of ovarian cancer is often difficult. The likelihood of peritoneal dissemination increases with the progress of ovarian cancer. With further progression, ovarian cancer metastasizes to the momentum, retroperitoneal lymph nodes, large intestine, small intestine, diaphragm, spleen, and other organs. Ovarian cancer has been considered a tumor that has a favorable response to chemotherapy, but more effective treatments are still being explored. Tumors use their own immune escape mechanism to evade host immunity. The immune checkpoint (IC) mechanism, one of the immune escape mechanisms, is established by programmed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) communication. It has been shown that inhibiting PD-1/PD-L1 communication in various malignancies produces antitumor effects. However, the antitumor effect of ICI monotherapy on ovarian cancer is limited in actual clinical practice. In this review, we describe a novel cancer immunotherapeutic agent that targets myeloid-derived suppressor cells (MDSCs).

A Novel Direct Approach to the Deep Uterine Vein in Laparoscopic Radical Hysterectomy.

STUDY OBJECTIVE: To describe a direct approach to the deep uterine vein in laparoscopic radical hysterectomy. DESIGN: Demonstration of the laparoscopic technique with narrated video footage. SETTING: Securing sufficient radicality is extremely important when performing a radical hysterectomy for cervical cancer, either by laparotomy or by minimally invasive surgery. The nerve-sparing Okabayashi radical hysterectomy (NS-RH) was originally aimed at achieving both radical resection and function preservation [1-3]. A key procedure when performing NS-RH is intraoperative identification of the relationship between the deep uterine vein and pelvic splanchnic nerve fibers [4]. With this in mind, a safe and easy method for identifying the crossing point of the deep uterine vein and pelvic splanchnic nerve in the initial phase of the surgery may greatly improve the safety and efficacy of functional preservation in NS-RH. Herein, we describe a minimally invasive "direct approach" to the deep uterine vein. INTERVENTIONS: Before undergoing the pelvic lymphadenectomy, all steps of laparoscopic radical hysterectomy were performed. First, we identified the ureter on the posterior peritoneum, and the peritoneum was dissected just above the ureter. By continuously exploring the pelvic cavity along the ureter, especially through the opening of the space below the ureter in a cranial to caudal direction, we could easily identify the deep uterine vein. This procedure also exposed the fibers of the hypogastric nerve, clarifying the relationship of these structures. CONCLUSION: Because the relationship between the deep uterine vein and nerve fibers is the most important guidepost of this surgery, their identification in the early phase of the surgery enables us to perform the subsequent procedure precisely and securely. This direct approach to the deep uterine vein can be easily and safely performed.

Mesonephric-like adenocarcinoma of the ovary in an elderly woman: A case report and a review of the literature.

Mesonephric-like adenocarcinoma (MLA) is a rare tumor that occurs in the uterine endometrium and ovary. It morphologically and immunohistochemically resembles cervical mesonephric adenocarcinoma (MA). Here, we present a case of MLA of the ovary along with a literature review. An asymptomatic 84-year-old woman presented with a pelvic mass, detected by computerized tomography. Magnetic resonance imaging demonstrated a polycystic mass with a solid component in the left adnexal region. The solid component showed low signal intensity on T2-weighted imaging and high signal intensity on diffusion-weighted imaging. We strongly suspected an ovarian malignant tumor; therefore, surgical resection of the uterus and adnexa was performed. Macroscopically, the tumor was predominantly solid with yellowish-tan cut surface. Microscopically, it showed a tubular pattern with intraluminal colloid-like material resembling MA. The tumor cells were negative for estrogen receptor, calretinin, and CD10 and positive for PAX8 and TTF-1. These findings are consistent with those of MLA.

Lymphoepithelioma-like carcinoma of uterine cervix: Preoperative diagnosis and course in three cases.

Lymphoepithelioma-like carcinoma of the uterine cervix is a rare variant of squamous cell carcinoma. Herein, we describe three cases of lymphoepithelioma-like carcinoma of the uterine cervix and review relevant literature. All three patients initially presented with postmenopausal bleeding. Gross appearances were endophytic with ulcerated mucosa in case 1, exophytic with polypoid morphology in case 2, and unremarkable even using colposcopy and hysteroscopy in case 3. Magnetic resonance imaging demonstrated well-demarcated cervical masses with high-intermediate intensity on T2-weighted images and high intensity on diffusion-weighted images in all three cases. In case 3, biopsy referring to local information from magnetic resonance images was required for preoperative diagnosis. We reviewed the literature of 59 lymphoepithelioma-like carcinoma cases in 19 papers published between 2001 and 2020. Preoperative diagnosis of lymphoepithelioma-like carcinoma is sometimes challenging, although magnetic resonance imaging findings may help determine the location of the tumor and obtain a successful biopsy.

Anti-VEGF therapy resistance in ovarian cancer is caused by GM-CSF-induced myeloid-derived suppressor cell recruitment.

BACKGROUND: The mechanism of resistance development to anti-VEGF therapy in ovarian cancer is unclear. We focused on the changes in tumour immunity post anti-VEGF therapy. METHODS: The frequencies of immune cell populations and hypoxic conditions in the resistant murine tumours and clinical samples were examined. The expression profiles of both the proteins and genes in the resistant tumours were analysed. The impact of granulocyte-monocyte colony-stimulating factor (GM-CSF) expression on myeloid-derived suppressor cell (MDSC) function in the resistant tumours was evaluated. RESULTS: We found a marked increase and reduction in the number of Gr-1 + MDSCs and CD8 + lymphocytes in the resistant tumour, and the MDSCs preferentially infiltrated the hypoxic region. Protein array analysis showed upregulation of GM-CSF post anti-VEGF therapy. GM-CSF promoted migration and differentiation of MDSCs, which inhibited the CD8 + lymphocyte proliferation. Anti-GM-CSF therapy improved the anti-VEGF therapy efficacy, which reduced the infiltrating MDSCs and increased CD8 + lymphocytes. In immunohistochemical analysis of clinical samples, GM-CSF expression and MDSC infiltration was enhanced in the bevacizumab-resistant case. CONCLUSIONS: The anti-VEGF therapy induces tumour hypoxia and GM-CSF expression, which recruits MDSCs and inhibits tumour immunity. Targeting the GM-CSF could help overcome the anti-VEGF therapy resistance in ovarian cancers.

UGT1A1 polymorphism has a prognostic effect in patients with stage IB or II uterine cervical cancer and one or no metastatic pelvic nodes receiving irinotecan chemotherapy: a retrospective study.

BACKGROUND: Uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) is a predictive biomarker for the side-effects of irinotecan chemotherapy, which reduces the volume of tumors harboring UGT1A1 polymorphisms. We aimed to determine whether UGT1A1 polymorphisms can predict progression-free survival in patients with local cervical cancer treated with irinotecan chemotherapy. METHODS: We retrospectively analyzed the data of 51 patients with cervical cancer treated at a single institution between 2010 and 2015. All patients were diagnosed with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IB1, IB2, IIA, or IIB squamous cell carcinoma, underwent radical hysterectomy, and received irinotecan chemotherapy as neoadjuvant and/or adjuvant treatment. All patients were examined for irinotecan side effects using UGT1A1 tests. Conditional inference tree and survival analyses were performed considering the FIGO stage, age, the UGT1A1 status, and the number of metastatic lymph nodes to determine primary factors associated with progression-free survival. RESULTS: The tree-structured survival model determined high recurrence-risk factors related to progression-free survival. The most relevant factor was ≥2 metastatic lymph nodes (p = 0.004). The second most relevant factor was UGT1A1 genotype (p = 0.024). Among patients with ≤1 metastatic lymph node, those with UGT1A1 polymorphisms benefited from irinotecan chemotherapy and demonstrated significantly longer progression-free survival (p = 0.020) than those with wild-type UGT1A1. CONCLUSIONS: Irinotecan chemotherapy might be beneficial in patients with cervical cancer, UGT1A1 polymorphisms, and ≤ 1 metastatic lymph nodes.

Uterine cervical squamous cell carcinoma without p16 (CDKN2A) expression: Heterogeneous causes of an unusual immunophenotype.

Immunohistochemically p16 (CDKN2A)-negative uterine cervical squamous cell carcinoma (SCC) is uncommon, and there are few reports about its pathological features. This study explored the causes of p16 negativity in such cases. We analyzed diagnostic tissue samples of five cases of p16-negative cervical SCC among 107 patients who underwent hysterectomy at Kyoto University Hospital between January 2010 and December 2015. The samples were subjected to immunohistochemical staining, in situ hybridization and a genetic analysis. Two of five cases were positive for human papilloma virus (HPV) by genotyping. One was positive for HPV56 with promoter hypermethylation of CDKN2A and co-existing Epstein-Barr virus infection. Another was positive for HPV6 categorized as low-risk HPV with condylomatous morphology. Among the remaining three cases, one had amplification of the L1 gene of HPV with promoter hypermethylation of CDKN2A and TP53 mutation, and one of the other two HPV-negative cases had a homozygous CDKN2A deletion, while the other was positive for p53 and CK7. p16-negativity of cervical SCC is often associated with an unusual virus infection status and CDKN2A gene abnormality.

Phosphorylation of STAT1 serine 727 enhances platinum resistance in uterine serous carcinoma.

Uterine serous carcinoma (USC) is a highly aggressive histological subtype of endometrial cancers harboring highly metastatic and chemoresistant features. Our previous study showed that STAT1 is highly expressed in USC and acts as a key molecule that is positively correlated with tumor progression, but it remains unclear whether STAT1 is relevant to the malicious chemorefractory nature of USC. In the present study, we investigated the regulatory role of STAT1 toward platinum-cytotoxicity in USC. STAT1 suppression sensitized USC cells to increase cisplatin-mediated apoptosis (p < 0.001). Furthermore, phosphorylation of STAT1 was prominently observed on serine-727 (pSTAT1-Ser727), but not on tyrosine-701, in the nucleus of USC cells treated with cisplatin. Mechanistically, the inhibition of pSTAT1-Ser727 by dominant-negative plasmid elevated cisplatin-mediated apoptosis by increasing intracellular accumulation of cisplatin through upregulation of CTR1 expression. TBB has an inhibitory effect on casein kinase 2 (CK2), which phosphorylate STAT1 at serine residues. Sequential treatment with TBB and cisplatin on USC cells greatly reduced nuclear pSTAT1-Ser727, enhanced intracellular accumulation of cisplatin, and subsequently increased apoptosis. Tumor load was significantly reduced by combination therapy of TBB and cisplatin in in vivo xenograft models (p < 0.001). Our results collectively suggest that pSTAT1-Ser727 may play a key role in platinum resistance as well as tumor progression in USC. Thus, targeting the STAT1 pathway via CK2 inhibitor can be a novel method for attenuating the chemorefractory nature of USC.

VISTA expressed in tumour cells regulates T cell function.

BACKGROUND: V-domain Ig suppressor of T cell activation (VISTA) is a novel inhibitory immune-checkpoint protein. VISTA expression on tumour cells and the associated regulatory mechanisms remain unclear. We investigated VISTA expression and function in tumour cells, and evaluated its mechanism and activity. METHODS: VISTA in tumour cells was assessed by tissue microarray analysis, immunohistochemical staining and western blot. A series of in vitro assays were used to determine the function of tumour-expressed VISTA. In vivo efficacy was evaluated in syngeneic models. RESULTS: VISTA was highly expressed in human ovarian and endometrial cancers. Upregulation of VISTA in endometrial cancer was related to the methylation status of the VISTA promoter. VISTA in tumour cells suppressed T cell proliferation and cytokine production in vitro, and decreased the tumour-infiltrating CD8+ T cells in vivo. Anti-VISTA antibody prolonged the survival of tumour-bearing mice. CONCLUSIONS: This is the first demonstration that VISTA is highly expressed in human ovarian and endometrial cancer cells, and that anti-VISTA antibody treatment significantly prolongs the survival of mice bearing tumours expressing high levels of VISTA. The data suggest that VISTA is a novel immunosuppressive factor within the tumour microenvironment, as well as a new target for cancer immunotherapy.

Solitary fibrous tumor arising from pelvic retroperitoneum: A report of two cases and a review of the literature.

Solitary fibrous tumors (SFT) rarely arise in the pelvis. Here, we report two cases of SFT arising from the pelvic retroperitoneum. The first case involves a 64-year-old woman diagnosed with a 5-cm pelvic mass. Magnetic resonance imaging revealed a solid and cystic mass with marked enhancement, but limited water restriction. During surgery, intraligamental tumor arising near the round ligament was resected. Pathologically, the tumor comprised dilated vessels and spindle-shaped cells positive for STAT6 and CD34. The second case involves a 53-year-old woman diagnosed with a 4.5-cm pelvic mass through computed tomography. Magnetic resonance imaging demonstrated a solid mass with multiple cysts with strong enhancement and slight water restriction. During surgery, the tumor was found in the retroperitoneum. Pathologically, spindle-shaped tumor cells positive for STAT6 and CD34 had proliferated around the prominent hyalinized vessels. Although rare in the pelvis, SFT should be suspected when a mass with strong enhancement is found.

Aggressive adult granulosa cell tumor of the ovary without a FOXL2 mutation: A case report.

We report a case of aggressive adult granulosa cell tumor (AGCT) of the ovary. On presentation, the tumor was localized in the right ovary; a total abdominal hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy were performed. While some areas of the tumor represented typical AGCT, other areas showed enlarged and hyperchromatic nuclei with numerous mitoses (>10/high-power field) with marked necrosis. The results of immunohistochemical analysis were compatible with AGCT, except that, in the necrotic portion, p53 was strongly positive, and the Ki-67 index was high. Four months after laparotomy, recurrent tumors developed in the bones, liver, lungs and dura mater. The patient responded well to chemotherapy consisting of five cycles of paclitaxel and carboplatin, but later, the tumors rapidly proliferated, and the patient died of disease 11 months after laparotomy. FOXL2 examination demonstrated that both portions of the primary tumor did not have a point mutation (402C→G) specific to AGCT.

Hysteroscopic morphological pattern reflects histological grade of endometrial cancer.

AIM: To examine the hysteroscopic morphological features in each histological grade of endometrial cancer, and to distinguish high- and low-grade cancer and low-grade cancer and atypical endometrial hyperplasia (AEH), using hysteroscopy. METHODS: In total, 135 patients who underwent hysterectomy after hysteroscopy were analyzed. They were divided into four categories: benign lesion; AEH; low-grade cancer, including endometrioid carcinoma grades 1 and 2 (G1/2); and high-grade cancer, including endometrioid carcinoma grade 3 and other high-grade carcinomas (G3/others). Three blinded gynecologic oncologists independently evaluated hysteroscopic video images for abnormal vessels, surface smoothness, papillary structure and polypoid structure. Prevalence rates of each finding were compared between the four categories. The accuracy of blind biopsy in outpatient settings and hysteroscopic endometrial biopsy in the four categories were also investigated. RESULTS: The number of patients with benign lesions, AEH, G1/2 and G3/others was 8, 7, 84 and 36, respectively. Patients with G3/others exhibited more polypoid (86% vs 61%, P = 0.0095) and less papillary (59% vs 80%, P = 0.023) structures than those exhibited by patients with G1/2. AEH and G1/2 were indistinguishable using hysteroscopy. Hysteroscopic biopsy was more accurate than outpatient biopsy in patients with G3/others (84% vs 52%, respectively, P = 0.010). Both biopsies were not sufficiently accurate to diagnose AEH (outpatient; 0%, hysteroscopic; 57%). CONCLUSION: Hysteroscopic papillary and polypoid structures can help distinguish between high- and low-grade cancer. Hysteroscopic differentiation between AEH and low-grade cancer is difficult. These findings are considerable in preoperative assessment to determine adequate surgical strategies.

Mucinous adenocarcinoma, gastric type of the uterine cervix: clinical features and HER2 amplification.

Mucinous adenocarcinoma, gastric type (GAS) is difficult to diagnose and shows poor prognosis. Trastuzumab, an anti-human epidermal growth factor type 2 (HER2) monoclonal antibody, is effective in HER2-positive stomach cancer. The objectives of this study were to identify the clinicopathological characteristics of GAS and to evaluate HER2 expression in GAS. We retrospectively reviewed 322 cervical cancer cases diagnosed at the Kyoto University Hospital from 2010 to 2016. The incidence, clinical factors including age, stage, and lymph node status, tumor markers, immunoreactive expression of MUC6, HIK1083, and HER2, and HER2 amplification were evaluated. Of the 322 cases of cervical cancer, 13 cases of the adenocarcinoma cases were diagnosed as GAS. Watery discharge, lower abdominal pain, CA19-9 elevation, and lymph node metastasis were frequently observed in GAS (p = 0.0226, p = 0.0400, p = 0.0346, and p = 0.0274, respectively). Immunohistochemistry showed positive MUC6 status in all 13 cases and positive HIK1083 status in 8 cases. The HER2 expression status was equivocal in six cases by immunohistochemistry and HER2 amplification was identified in one case. GAS exhibits frequent lymph node metastasis and clinical symptoms such as watery discharge and lower abdominal pain, high levels of CA19-9. In addition, some parts of GAS exhibit HER2 amplification.