BackgroundC3H mice have been frequently used in cancer studies as animal models of spontaneous liver tumors and chemically induced hepatocellular carcinoma (HCC). Epigenetic modifications, including DNA methylation, are among pivotal control mechanisms of gene expression leading to carcinogenesis. Although information on somatic mutations in liver tumors of C3H mice is available, epigenetic aspects are yet to be clarified.MethodsWe performed next generation sequencing-based analysis of DNA methylation and microarray analysis of gene expression to explore genes regulated by DNA methylation in spontaneous liver tumors of C3H mice. Overlaying these data, we selected cancer-related genes whose expressions are inversely correlated with DNA methylation levels in the associated differentially methylated regions (DMRs) located around transcription start sites (TSSs) (promoter DMRs). We further assessed mutuality of the selected genes for expression and DNA methylation in human HCC using the Cancer Genome Atlas (TCGA) database.ResultsWe obtained data on genome-wide DNA methylation profiles in the normal and tumor livers of C3H mice. We identified promoter DMRs of genes which are reported to be related to cancer and whose expressions are inversely correlated with the DNA methylation, including Mst1r, Slpi and Extl1. The association between DNA methylation and gene expression was confirmed using a DNA methylation inhibitor 5-aza-2′-deoxycytidine (5-aza-dC) in Hepa1c1c7 cells and Hepa1-6 cells. Overexpression of Mst1r in Hepa1c1c7 cells illuminated a novel downstream pathway via IL-33 upregulation. Database search indicated that gene expressions of Mst1r and Slpi are upregulated and the TSS upstream regions are hypomethylated also in human HCC. These results suggest that DMRs, including those of Mst1r and Slpi, are involved in liver tumorigenesis in C3H mice, and also possibly in human HCC.ConclusionsOur study clarified genome wide DNA methylation landscape of C3H mice. The data provide useful information for further epigenetic studies of mice models of HCC. The present study particularly proposed novel DNA methylation-regulated pathways for Mst1r and Slpi, which may be applied not only to mouse HCC but also to human HCC.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4221-0) contains supplementary material, which is available to authorized users.

Ovarian metastasis (OM) from breast cancer accounts for 3-38% of all ovarian neoplasms and is associated with various characteristic clinical presentations, such as pseudo-Meigs syndrome and Krukenberg tumor. Accurate diagnosis of OM may be challenging, as such lesions are frequently asymptomatic until they reach a large size. Occasionally, metastatic ovarian cancer is detected prior to the diagnosis of the primary tumor. Immunohistochemistry plays an important role in distinguishing primary ovarian tumors from extraovarian tumor metastases and may be helpful for identifying the primary tumor site. We herein report a case of OM from breast cancer masquerading as primary ovarian cancer. However, the correct diagnosis was made based on histopathological and immunohistochemical examinations. The patient had bilateral breast cancer, namely invasive lobular carcinoma of the left breast and ductal carcinoma of the right breast. Due to the presence of bilateral synchronous breast tumors, the possibility that the patient had hereditary breast and ovarian cancer syndrome or other relevant genetic factors was considered. Immunohistochemistry plays a key role in distinguishing between primary ovarian tumors and OM, and it was also important for confirming the metastatic nature of the ovarian lesion and diagnosing the primary tumor in the present study.

Although a rare disease, the diagnosis of FS should be considered in the case of primary amenorrhea with nephropathy. Prophylatic gonadectomy is recommended due to the high risk of gonadoblastoma in the dysgenetic gonad.

It is relatively uncommon to treat patients with a preoperative diagnosis of benign leiomyoma that is then unexpectedly rediagnosed as malignant in postoperative histology. We report the case of a 55-year-old woman with low-grade endometrial stromal sarcoma who had been diagnosed as having uterine leiomyoma with myxoid degeneration by preoperative magnetic resonance imaging (MRI). She underwent a laparoscopic hysterectomy. The uterus, after being placed in a retrieval bag, was transvaginally morcellated to prevent spillage of the contents, as the MRI image appeared somewhat atypical. A retrospective survey of MRI findings affirmed that the muscle tissue had the appearance of a low-intensity band-like structure: bag of worms appearance. She underwent a laparoscopic bilateral salpingo-oophorectomy and remains recurrence-free. With somewhat atypical preoperative MRI, it is essential to prevent the spillage of the tumor content as no definitive preoperative exclusion of unsuspected mesenchymal malignancies is feasible.

Squamous cell carcinoma of the endometrium is extremely rare, accounting for approximately 1% of uterine body malignancies. The present report describes a case of squamous cell carcinoma of the uterine body arising from ichthyosis due to persistent pyometra. A 68-year-old Japanese woman, gravida 1 para 1, was referred to the Gynecological Department of Tokyo Women's Medical University, due to watery brown vaginal discharge which had persisted for 10 days. Pelvic magnetic resonance (MRI) imaging revealed a tumorous lesion occupying the cervical uteri, measuring 3 cm in diameter, and pyometra. The endometrial biopsy specimen obtained after drainage of the purulent fluid in the uterus was insufficient for obtaining a definitive pathological diagnosis. Under a clinical diagnosis of cervical tumor and pyometra, total transabdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histopathologically, two primary cancers were diagnosed, i.e., cervical endometrioid carcinoma and squamous cell carcinoma of the endometrium. The patient was treated with additional chemotherapy with carboplatin (area under the curve, 6) and paclitaxel (175 mg/m 2). The patient has remained alive, without recurrence, for 1 year to date. In this case, preexisting cervical endometrioid carcinoma caused stenosis of the uterine orifice and also resulted in pyometra. The uterine body squamous cell carcinoma appeared to have been caused by persistent inflammatory stimuli to the endometrium. One must be cautious regarding cancer in elderly postmenopausal females presenting with pyometra. The findings in this case report suggest that chronic inflammation of the endometrium may be associated with primary squamous cell carcinoma of the endometrium.