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Synchronous endometrial and ovarian cancer (SEOC) is a rare entity among gynecological cancers, which exhibits endometrioid histology in its early stages and generally has a good prognosis. However, diagnosis is difficult and recent reports have demonstrated that most clinically diagnosed cases of SEOC have clonally related cancers, indicating metastatic cancer. The association of SEOC with Lynch syndrome is also not clearly understood. We herein present the case of a 41-year-old SEOC patient with MSH2 mutation. The endometrial cancer was an endometrioid adenocarcinoma and the ovarian cancer was mainly endometrioid, but also included a clear cell carcinoma with a borderline clear cell adenofibromatous component, indicating primary ovarian cancer. Both tumors exhibited microsatellite instability (MSI) and loss of expression of MSH2 and MSH6. The patient had a family history of colorectal and gastric cancers. Genetic analysis revealed a germline mutation in exon 6 of MSH2 (c.1042C>T, p.Gln348*) and the patient was diagnosed with Lynch syndrome. This MSH2 mutation has only been registered in one case in the InSiGHT variant databases and has not been reported in a gynecological tumor or SEOC to date. This case is a rare example of a patient with genetically diagnosed Lynch syndrome who also developed SEOC. This synchronous cancer is not common, but it may be caused by Lynch syndrome. Testing for MSI and immunohistochemistry for mismatch repair deficiency is necessary in cases with suspected SEOC.

Synchronous endometrial and ovarian cancer (SEOC) is a rare entity among gynecological cancers, which exhibits endometrioid histology in its early stages and generally has a good prognosis. However, diagnosis is difficult and recent reports have demonstrated that most clinically diagnosed cases of SEOC have clonally related cancers, indicating metastatic cancer. The association of SEOC with Lynch syndrome is also not clearly understood. We herein present the case of a 41-year-old SEOC patient with MSH2 mutation. The endometrial cancer was an endometrioid adenocarcinoma and the ovarian cancer was mainly endometrioid, but also included a clear cell carcinoma with a borderline clear cell adenofibromatous component, indicating primary ovarian cancer. Both tumors exhibited microsatellite instability (MSI) and loss of expression of MSH2 and MSH6. The patient had a family history of colorectal and gastric cancers. Genetic analysis revealed a germline mutation in exon 6 of MSH2 (c.1042C>T, p.Gln348*) and the patient was diagnosed with Lynch syndrome. This MSH2 mutation has only been registered in one case in the InSiGHT variant databases and has not been reported in a gynecological tumor or SEOC to date. This case is a rare example of a patient with genetically diagnosed Lynch syndrome who also developed SEOC. This synchronous cancer is not common, but it may be caused by Lynch syndrome. Testing for MSI and immunohistochemistry for mismatch repair deficiency is necessary in cases with suspected SEOC.

Selective aberrant genetic effects that do not depend on abnormal DNA sequences are referred to as epigenetic abnormalities and are involved in carcinogenesis. In uterine cancer, various genes involved in apoptosis, cell cycle, DNA repair, cell proliferation and cell adhesion are abnormally methylated, resulting in gene silencing. Reversal of such epigenetic abnormalities in cancer cells is a potential strategy for cancer therapy, and studies on epigenetic abnormalities and treatment methods in uterine cancer are in progress. These include the evaluation of 5-hydroxymethylcytosine, which is present in cancer tissues at lower levels compared with those in normal tissues, as a prognostic marker in cervical cancer; combination therapy with 5-azacytidine and cisplatin; combination treatment focusing on tumor necrosis factor-related apoptosis-inducing ligand in cervical cancer; studies focusing on DNA mismatch repair in endometrial cancer; and use of a demethylating agent to reactivate tumor suppressor genes and inhibit tumor proliferation. Detection of epigenetic changes using biomarkers may be used for histological classification, evaluation of disease progression and identification of compounds that are able to modulate epigenetic changes and may be useful for uterine cancer treatment.

Lynch syndrome is a hereditary ovarian cancer with a prevalence of 0.9-2.7%. Lynch syndrome accounts for 10-15% of hereditary ovarian cancers, while hereditary breast and ovarian cancer syndrome accounts for 65-75% of these cancers. The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers, and ovarian cancer is not listed in the Amsterdam Criteria II. More than half of sporadic ovarian cancers are diagnosed in stage III or IV, but ≥80% of ovarian cancers in Lynch syndrome are diagnosed in stage I or II. Ovarian cancers in Lynch syndrome mostly have non-serous histology and different properties from those of sporadic ovarian cancers. A screening method for ovarian cancers in Lynch syndrome has yet to be established and clinical studies of prophylactic administration of oral contraceptives are not available. However, molecular profiles at the genetic level indicate that ovarian cancer in Lynch syndrome has a more favorable prognosis than sporadic ovarian cancer. Inhibitors of the phosphatidylinositol 3-kinase/mammalian target of the rapamycin pathway and anti-epidermal growth factor antibodies may have efficacy for the disease. To the best of our knowledge, this is the first review focusing on ovarian cancer in Lynch syndrome.

There is currently insufficient evidence to recommend a specific chemotherapeutic regimen as standard treatment for uterine sarcomas. In this study, we investigated the toxicity and effectiveness of ifosfamide, adriamycin and cisplatin (IAP therapy) in patients with progressive and recurrent uterine sarcoma. A total of 11 patients with progressive or recurrent uterine sarcoma containing leiomyosarcoma (LMS), undifferentiated endometrial sarcoma (UES) or adenosarcoma, who were diagnosed at our institution, were retrospectively investigated. We recorded the adverse events, response rate and progression-free survival in these cases. The histological types included LMS (54.5%), adenosarcoma (27.3%) and UES (18.2%). Grade ≥3 leukopenia or neutropenia were observed in all the cases, febrile neutropenia developed in 45.5% of the patients and grade 4 thrombocytopenia developed in 3 cases (27.3%). With IAP therapy, the response rate was 36.4% and the disease control rate was 90.9%. Therefore, IAP therapy may be a viable option as chemotherapy for uterine sarcoma.

Endometrial cancer is a common gynecological malignant tumor in Western countries and its incidence has also been on the increase in Asia. Genetic abnormalities related to onset and progression of malignancy in the endometrial membrane and signaling system have been identified and the developmental mechanism of endometrial cancer is becoming elucidated. The identification of the molecules related to these abnormalities has led to new potential treatment regimens for endometrial cancer, using molecular-targeted drugs. The current chemotherapy for endometrial cancer often causes systemic side effects that require discontinuation of the treatment. Furthermore, a treatment regimen for cancers of rare histological types has not been established. Recent studies on endometrial cancer revealed patterns of genetic disorders that differ among the histological types. Genetic and molecular information that underlie pathological changes and is associated with DNA mismatch repair genes and epigenetic regulation was also identified. Targeting of these mechanisms with molecular-targeted drugs has been performed with the aim of linking treatment to the carcinogenic mechanism at the molecular and genetic levels. However, the response rates with single-agent therapy are generally low and several problems remain unresolved. Trials of combinations of molecular-targeted drugs with currently available treatments and identification of factors determining sensitivity are required to overcome these difficulties.