Search

Clear cell carcinoma of the ovary (CCC) is a histologic subtype of epithelial ovarian cancer with a distinct clinical behavior. There are marked geographic differences in the prevalence of CCC. The CCC is more likely to be detected at an early stage than high-grade serous cancers, and when confined within the ovary, the prognosis is good. However, advanced disease is associated with a very poor prognosis and resistance to standard treatment. Cytoreductive surgery should be performed for patients with stage II, III, or IV disease. An international phase III study to compare irinotecan/cisplatin and paclitaxel/carboplatin as adjuvant chemotherapy for stage IIV CCC has completed enrollment (GCIG/JGOG3017). Considering the frequent PIK3CA mutation in CCC, dual inhibitors targeting PI3K, AKT in the mTOR pathway, are promising. Performing these trials and generating the evidence will require considerable international collaboration. [ABSTRACT FROM AUTHOR]

Uterine serous carcinoma (USC) represents a rare and aggressive histologic subtype of endometrial cancer, associated with a poor prognosis. This article critically reviews the literature pertinent to the epidemiology, pathology, molecular biology, diagnosis, management, and perspectives of patients with USC.As one of a series of The Gynecologic Cancer InterGroup (GCIG) Rare Tumor Working Group in London, November 2013, we discussed about USC many times with various experts among international GCIG groups.Both USC and approximately 25% of high-grade endometrioid tumors represent extensive copy number alterations, few DNA methylation changes, low estrogen and progesterone levels, and frequent P53mutations. Uterine serous carcinoma shares molecular characteristics with ovarian serous and basal-like breast carcinomas. In addition to optimal surgery, platinum- and taxane-based chemotherapy should be considered in the treatment of both early- and advanced-stage disease. The combination of radiation and chemotherapy appears to be associated with the highest survival rates. The role of radiation therapy in the management of this disease, with a high propensity for distant failures, remains elusive.Uterine serous carcinoma is a unique and biologically aggressive subtype of endometrial cancer and should be studied as a distinct entity. Futures studies should identify the optimized chemotherapy and radiation regimens, sequence of therapy and schedule, and the role of targeted biologic therapy. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is the most common cancer of the female genital tract. However, no screening method for EC has been established yet. In this study, we evaluated the cell-free DNA in EC.Fifteen healthy individuals, 9 with benign gynecologic diseases, and 53 with ECs were included in this study. Alu sequences in free DNA fragments were used as surrogate markers, and cell-free DNA density was measured by quantitative real-time polymerase chain reaction.The cell-free DNA levels in ECs tended to be higher than in benign condition (healthy individuals + benign gynecologic diseases, n = 24; P = 0.095). There was no significant difference in cell-free DNA among stage or histological grade of EC, and no significant change in cell-free DNA before and after operation (P = 0.25): Moreover, in 19 ECs, cell-free DNA decreased after operation, however, in 6 ECs, cell-free DNA did not decrease. Three ECs recurred, and cell-free DNA did not decrease in these cases.Measurement of cell-free DNA is not useful for EC screening; however, the change of cell-free DNA in a patient may be a prognostic biomarker of EC. [ABSTRACT FROM AUTHOR]

Host antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8+ cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients.The study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4+FOXP3+ cells were identified as Tregs in this study. The numbers of CD8+ cells, CD4+ cells, and Tregs as well as the Treg/CD8+ and Treg/CD4+ ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis.Of the 53 patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The CD8+ and CD4+ cell counts, Treg count, and Treg/CD8+ and Treg/CD4+ ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8+ ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8+ ratios (P < 0.05).The Treg count and Treg/CD8+ ratio may be new prognostic factors for endometrial cancer. [ABSTRACT FROM AUTHOR]

To clarify the preoperative differential diagnosis and management of minimal deviation adenocarcinoma (MDA) and lobular endocervical glandular hyperplasia (LEGH), a multicenter study was performed.A total of 112 patients who underwent conization or a hysterectomy for suspected MDA were collected from 24 hospitals. The pathological diagnosis in each case was determined by a central pathological review board. The diagnostic significance of clinicopathologic findings including results of magnetic resonance imaging (MRI), Papanicolaou (Pap) smears, and testing for gastric mucin was analyzed.The central pathological review identified 37 cases of Nabothian cyst or tunnel cluster, 54 cases of LEGH, 6 cases of MDA, 11 cases of adenocarcinoma, and 4 cases of benign disease. Lobular endocervical glandular hyperplasia was often associated with adenocarcinoma in situ, MDA, and mucinous adenocarcinoma. Three MDA patients had a recurrence, whereas none of LEGH patients had a recurrence irrespective of the type of surgery. On MRI, LEGH appeared as a characteristic multicystic lesion with an inner solid component, whereas MDA showed a predominantly solid pattern. A Pap smear or gastric mucin alone had limited diagnostic power. However, a combination of these findings is useful; that is, a cystic structure with inner solid components on MRI associated with mild glandular atypia and gastric mucin strongly suggested LEGH (24/26, 92%). A solid structure with atypical glandular cells was indicative of MDA or adenocarcinoma (5/5, 100%).The combination of MRI, Pap smears, and gastric mucin will improve the accuracy of the preoperative diagnosis of MDA and LEGH. Patients suspected of having LEGH may need to be treated with less aggressive methods.Abbreviations: MDA - Minimal deviation adenocarcinoma, LEGH - Lobular endocervical glandular hyperplasia, NC - Nabothian cyst, TC - Tunnel cluster, NILM - Negative for intraepithelial lesion, AGCs - Atypical glandular cells, AIS - Adenocarcinoma in situ, CPR - Central pathological review, Pap - Papanicolaou, MRI - Magnetic resonance imaging [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to examine the relation between cofilin 1 expression and progression-free survival in advanced epithelial ovarian cancer. We performed quantitative reverse transcriptase polymerase chain reaction and immunohistochemical analysis in 78 patients with advanced epithelial ovarian cancer (excluding those with mucinous and clear-cell types). All patients received the standard therapy, including staging laparotomy and adjuvant chemotherapy consisting of carboplatin and paclitaxel. Of 78 samples, RNA from 62 samples was available for reverse transcriptase polymerase chain reaction analysis. We defined cofilin 1 high expression as relative gene expression equal to or higher than the median and low expression as gene expression lower than median. The progression-free survival was longer in cofilin 1 low-expression cases than in high-expression cases (P = .039). Multivariate analysis demonstrated that stage and cofilin 1 expression were significant predictors of progression-free survival. Of the 78 samples, 54 were appropriate for immunohistochemical study. In 35 of those 54 cases, cofilin 1 protein expression was detected. The progression-free survival was longer in cofilin 1 protein-negative cases than in protein-positive cases (P = .042). Expression of cofilin 1 may predict the progression-free survival of patients with advanced epithelial ovarian cancer receiving standard therapy. [ABSTRACT FROM AUTHOR]

Incidence of lymph node metastasis is relatively high even in early-stage epithelial ovarian cancers (EOC). Lymphadenectomy is important in the surgical treatment of EOC; however, the exact role of lymphadenectomy in the management of EOC remains unclear. In this study, we evaluated lymph node metastasis in stages I and II EOC patients.Seventy-nine patients with stage I/II EOC underwent initial surgery, and 68 patients received adjuvant platinum and taxane chemotherapy after surgery at Keio University Hospital. The patients were evaluated with respect to age at diagnosis, clinical stage, histology, histological grade, and tumor laterality.Of the 79 patients, 10 (12.7%) had lymph node metastasis. Of these, 4 (5.1%) had lymph node metastasis in paraaortic lymph node (PAN) only, 1 (1.3%) in pelvic lymph node (PLN) only, and 5 (6.3%) in both PAN and PLN. The incidence of serous-type lymph node metastasis in PAN, PAN + PLN, and total was higher than nonserous type (25% vs 1.5%, P < 0.0001; 25% vs 3.0%, P = 0.001; 50% vs 5.9%, P < 0.0001). However, there was no significant difference between lymph node status and T factor or histological grade. In 78% of patients (7/9), metastases in contralateral lymph nodes were present (contralateral, 2; bilateral, 5). There was no significant difference in progression-free survival between node-positive and node-negative groups (P = 0.47).Based on diagnostic value, the result suggests that the role of lymphadenectomy might differ by histological type, as its therapeutic effect might be unclear. A multicenter analysis is essential for confirmation. [ABSTRACT FROM AUTHOR]