Gastric signet-ring cell carcinoma metastasis to bilateral ovarian granulosa cell tumors.

Tumor-to-tumor metastasis is a rare phenomenon. On the basis of our review of international literature, there have been 7 reports of tumor-to-tumor metastasis cases involving ovary neoplasms as the recipient. However, an ovarian granulosa cell tumor has not been reported to be a recipient. Here, we report the first case of gastric signet-ring cell carcinoma metastasis to a bilateral ovarian granulosa cell tumor. Awareness of this phenomenon is important to avoid incorrect diagnoses when encountering unusual morphologic features in ovarian granulosa cell tumors.

Epigenetic reprogramming of human lung cancer cells with the extract of bovine parthenogenetic oocytes.

The tumour suppressor gene silencing and proto-oncogene activation caused by epigenetic alterations plays an important role in the initiation and progression of cancer. Re-establishing the balance between the expression of tumour suppressor genes and proto-oncogenes by epigenetic modulation is a promising strategy for cancer treatment. In this study, we investigated whether cancer cells can be epigenetically reprogrammed by oocyte extract. H460 human lung cancer cells were reversibly permeabilized and incubated with the extract of bovine parthenogenetic oocytes. Bisulphite sequencing showed that bovine parthenogenetic oocyte extract induced significant demethylation at the promoters of the tumour suppressor genes RUNX3 and CDH1, but not at the promoter of the oncogenic pluripotency gene SOX2. Chromatin immunoprecipitation showed that the histone modifications at RUNX3 and CDH1 promoters were modulated towards a transcriptionally activating state, while those at SOX2 promoter towards a transcriptionally repressive state. Correspondingly, bovine parthenogenetic oocyte extract reversed the epigenetic silencing of RUNX3 and CDH1, and repressed the expression of SOX2. At the functional level, proliferation, anchorage-independent growth, migration and invasion of H460 cells was strongly inhibited. These results indicate that bovine parthenogenetic oocyte extract changes the expression patterns of tumour suppressor and oncogenic genes in cancer cells by remodelling the epigenetic modifications at their promoters. Bovine parthenogenetic oocyte extract may provide a useful tool for epigenetically reprogramming cancer cells and for dissecting the epigenetic mechanisms involved in tumorigenesis.

ERBB2 is a potential diagnostic and prognostic biomarker in renal clear cell carcinoma.

Renal clear cell carcinoma (ccRCC) is a common parenchymal tumor of the kidney, and the discovery of biomarkers for early and effective diagnosis of ccRCC can improve the early diagnosis of patients and thus improve long-term survival. Erb-b2 receptor tyrosine kinase 2 (ERBB2) mediates the processes of cell proliferation, differentiation, and apoptosis inhibition. The purpose of this study was to investigate the diagnostic and prognostic role of ERBB2 in ccRCC. We analyzed the expression levels of ERBB2 in various cancers from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RNA-seq data were analyzed using R packages to identify differentially expressed genes between the high and low ERBB2 expression groups in the TCGA-KIRC dataset. Spearman correlation analysis was performed to determine the correlation between ERBB2 expression and immune cell infiltration, immune checkpoint expression, and PTEN expression. DNA methylation changes and genetic alterations in ERBB2 were assessed using the MethSurv and cBioPortal databases. Logistic regression analysis was performed to determine the correlation between ERBB2 expression and the clinicopathological characteristics of ccRCC patients. The diagnostic and prognostic value of ERBB2 was assessed using Kaplan‒Meier (K‒M) survival curves, diagnostic ROC curves, time-dependent ROC curves, nomogram models, and Cox regression models. The expression level of ERBB2 is lower in tumor tissues of ccRCC patients than in the corresponding control tissues. Differentially expressed genes associated with ERBB2 were significantly enriched in the pathways "BMP2WNT4FOXO1 pathway in primary endometrial stromal cell differentiation" and "AMAN pathway". In ccRCC tissues, ERBB2 expression levels were associated with immune cell infiltration, immune checkpoints, and PTEN. The DNA methylation status of 10 CpG islands in the ERBB2 gene was associated with the prognosis of ccRCC. ERBB2 expression levels in ccRCC tissues were associated with race, sex, T stage, M stage, histological grade, and pathological stage. Cox regression analysis showed that ERBB2 was a potential independent predictor of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in ccRCC patients. ROC curve analysis showed that the expression level of ERBB2 could accurately distinguish between ccRCC tissue and adjacent normal renal tissue. Our study showed that ERBB2 expression in ccRCC tissues can be of clinical importance as a potential diagnostic and prognostic biomarker.

Histopathologic characteristics and immunotypes of perivascular epithelioid cell tumors (PEComa).

OBJECTIVES: In order to provide further evidence for the origin and differentiation of PEComa, the clinicopathologic and immunophenotype findings were analyzed in 26 cases with literature review. METHODS: Immunohistochemistry and special staining were used. RESULTS: Multinucleated giant cells and polymorphism were scattered visibly in 53.8% and 76.9% of the cases and spotty necrosis and hemorrhage were observed in 38% of the cases. Capsular micro-invasion was detected in 46% cases accompanied by hemorrhage and/or necrosis in the tumors with diameters larger than 5 cm. It was also found that 100% of cases diffusely expressed SMA, Melan-A, and vimentin except one negative for HMB-45. The tumor cells partly expressed CD56, CD99, desmin, and S-100 and were negative for CK-pan, TFE3, CD117, CD44, and CD34. Clinical follow-up found that 22 out of 23 patients were alive, with no recurrence or progression, ranging from 42 to 82 months. However, one patient died from leukemia. CONCLUSIONS: In this study, the histopathologic features with the co-expressions of SMA and melanin, were the diagnostic basis of PEComas. The interspersed expressions of desmin and S-100 were helpful for the differential diagnosis of leiomyoma and neuroma. The expressions of S-100, CD56, and CD99 supported the origins of the pluripotent cells from the neural crests. Tumors larger than 5 cm in diameter with micro-hemorrhaging/necrosis and micro-capsular invasions should be considered either uncertain or of malignant potential. The spontaneous rupturing of blood vessels may be related to the amyloidosis and desmin negative expression, and broken elastic fibers.

High Spy1 expression predicts poor prognosis in colorectal cancer.

BACKGROUND: Spy1 (SPDYA) is a new discovered cell cycle protein capable of promoting cell proliferation dependent on cyclin-dependent kinase-2 activation. However, to the best of our knowledge, the expression of Spy1 in colorectal cancer (CRC) tissues remains virtually unknown. MATERIALS AND METHODS: In this retrospective study, we investigated the mRNA and protein expression levels of Spy1 in CRC tissues and corresponding non-cancerous tissues with the analyses of quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. In our research, the prognostic significances of Spy1 expression were further explored by univariate and multivariate survival analyses of 203 patients who were followed up. RESULTS: The results demonstrated that the levels of Spy1 mRNA were significantly higher in CRC tissues compared with corresponding non-cancerous tissues (p=0.0002). The results of immunohistochemistry demonstrated that the expressions of Spy1 were significantly associated with clinicopathological parameters, including T stage (χ2=7.126, p=0.028) and TNM stage (χ2=9.461, p=0.009). Kaplan-Meier analysis results indicated that high Spy1 expression (HR=2.573, p<0.001) and TNM stage (HR=1.494, p=0.011) were independent factors to predict poor prognosis for patients with CRC. CONCLUSION: We concluded that high Spy1 expression is significantly associated with unfavorable prognosis in CRC and could serve as a potential prognostic marker in clinical diagnosis of CRC.

Specific reversal of tumor-suppressor gene promoter hypermethylation with bovine oocyte extract.

Epigenetic silencing of tumor-suppressor genes by promoter hypermethylation contributes considerably to the initiation and progression of cancer. Nucleoside analogs, the most widely used DNA methylation inhibitors, have the drawbacks of inducing repetitive sequence hypomethylation. Here, we aimed to specifically reverse tumor-suppressor gene (TSG) promoter hypermethylation with bovine oocyte extract. H460 human lung cancer cells were reversibly permeabilized and incubated with bovine oocyte extract for 3.5 h. The extract treatment led to significant demethylation of the hypermethylated promoters of the TSGs RUNX3, CDH1, RASSF1A and WIF1; however, the methylation levels of repetitive sequences were not affected. The promoter demethylation induced by bovine oocyte extract substantially upregulated the expression of RUNX3, CDH1, RASSF1A and WIF1, and significantly inhibited the anchorage-independent proliferation, migration and invasion of H460 cells. This study demonstrates that bovine oocyte extract can reverse the malignant phenotype by serving as an efficient and safe DNA demethylator. The active demethylation activity of bovine oocyte extract is valuable for dissecting the epigenetic alterations in cancer cells and developing novel safe anticancer drugs based on epigenetic mechanisms.