DNA methylation plays an important role in gene expression, chromatin stability, and genetic imprinting. In mammals, DNA methylation patterns are written and regulated by DNA methyltransferases (DNMTs), including DNMT1, DNMT3A and DNMT3B. Recent emerging evidence shows that defects in DNMTs are involved in tumor transformation and progression, thus indicating that epigenetic disruptions caused by DNMT abnormalities are associated with tumorigenesis. Herein, we review the latest findings related to DNMT alterations in cancer cells and discuss the contributions of these effects to oncogenic phenotypes.

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Emerging evidence suggests a decline of ERβ expression in various peripheral cancers. ERβ has been proposed as a cancer brake that inhibits tumor proliferation. In the current study, we have identified ERβ5 as the predominant isoform of ERβ in human glioma and its expression was significantly increased in human glioma as compared with non-neoplastic brain tissue. Hypoxia and activation of hypoxia inducible factor (HIF) increased ERβ transcription in U87 cells, suggesting elevated ERβ expression in glioma might be induced by the hypoxic stress in the tumor. Over-expression of either ERβ1 or ERβ5 increased PTEN expression and inhibited activation of the PI3K/AKT/mTOR pathway. In addition, ERβ5 inhibited the MAPK/ERK pathway. In U87 cells, ERβ1 and ERβ5 inhibit cell proliferation and reduced cells in the S+G2/M phase. Our findings suggest hypoxia induced ERβ5 expression in glioma as a self-protective mechanism against tumor proliferation and that ERβ5 might serve as a therapeutic target for the treatment of glioma.

Abstract. Metaplastic carcinoma of the breast is a rare form of breast cancer. The aim of the present study was to investigate the imaging and pathological features of metaplastic carcinoma. The features identified on mammography and sonography were retrospectively reviewed in 13 women with metaplastic carcinoma of the breast. The results from the mammographs and sonographs were additionally evaluated using immunohistochemical staining for the expression of the estrogen receptor (ER) and progesterone receptor (PR), receptor tyrosine-protein kinase erbB-2 (CerbB-2) and P53. The most common features observed in the mammographs were as follows: Irregular and oval shaped masses, 53.8 and 46.2%, respectively; spiculated and circumscribed margins, each 30.8%; and high and marginally high density masses, 69.2 and 30.8%, respectively. The most common sonography features observed were as follows: Hypoechoic masses, 84.6%; complex echogenicity, 76.9%; irregular, round and oval shaped masses, 69.2, 30.8 and 30.8%, respectively; indistinct and circumscribed margins, 53.8 and 46.2%, respectively; an abundant blood flow, 53.8%; and posterior acoustic enhancement, 61.5%. The immunohistochemical (IHC) profile for 13 patients demonstrated that ER was not expressed in 100% of patients, PR and CerbB-2 were not present in 92.3% of patients, and P53 was present in 63.6% of patients. Therefore, metaplastic carcinoma of the breast exhibits more benign IHC features compared with invasive ductal carcinoma. In addition, it may be challenging to diagnose patients that do not possess posterior acoustic enhancement or express hormone receptors from other types of breast cancer. IntroductionMetaplastic carcinoma of the breast is a rare form of breast cancer and possesses a poorer prognosis than other common types of breast cancer (1). Metaplastic carcinoma exhibits the metaplastic transformation of glandular epithelium to squamous epithelium and mesenchymal tissue, and accounts for <5% of all breast cancers (2) and may contain glandular and non-glandular components with mixed epithelial and mesenchymal tissue. Involvement of the axillary lymph node is rare, with hematogenous metastasis occurring more commonly in cases of metaplastic carcinoma (1,3). Metaplastic carcinoma demonstrates a poorer prognosis and a higher risk of recurrence compared with other types of breast cancer (3). It typically presents as triple negative, therefore the effects of hormonotherapy are limited (3,4). Due to the heterogeneity of metaplastic carcinoma and its increased complexity compared with more common types of breast cancer, mixed chemotherapy regimens and dose schedules may be more effective and appropriate (2). Due to the distinction in surgical treatment and chemotherapy between metaplastic carcinoma and other breast cancers, it is particularly important to diagnose the tumor correctly (2). Metaplastic carcinoma demonstrates a number of benign features similar to invasive ductal carcinoma in mammograms and sonograms, and subsequently may be misdiagnosed as ...

This short series suggests the following: (1) RDD should be included in the differential diagnosis of lesions mimicking intracranial/spinal meningiomas or inflammatory lesions, especially in children; (2) the definitive diagnosis is based on histopathology and immunocytochemistry; (3) surgical resection seems to be the most effective therapy; (4) the exact etiology and adjuvant therapy for relapsing/incompletely resected lesions remain to be established.

BACKGROUND. Lower-grade gliomas (LGGs) vary widely in terms of the patient's overall survival (OS). There is no current, valid method that could exactly predict the survival. The effects of intratumoral immune infiltration on clinical outcome have been widely reported. Thus, we aim to develop an immune infiltration signature to predict the survival of LGG patients. METHODS. We analyzed 1216 LGGs from 5 public data sets, including 2 RNA sequencing data sets and 3 microarray data sets. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select an immune infiltration signature and build a risk score. The performance of the risk score was assessed in the training set (329 patients), internal validation set (140 patients), and 4 external validation sets (405, 118, 88, and 136 patients). RESULTS. An immune infiltration signature consisting of 20 immune metagenes was used to generate a risk score. The performance of the risk score was thoroughly verified in the training and validation sets. Additionally, we found that the risk score was positively correlated with the expression levels of TGF-β and PD-L1, which were important targets of combination immunotherapy. Furthermore, a nomogram incorporating the risk score, patient's age, and tumor grade was developed to predict the OS, and it performed well in all the training and validation sets (C-index: 0.873, 0.881, 0.781, 0.765, 0.721, and 0.753). CONCLUSION. The risk score based on the immune infiltration signature has reliable prognostic and predictive value for patients with LGGs and is a potential biomarker for the cotargeting immunotherapy.

Background Evaluating tumor‐infiltrating lymphocytes (TILs) in patients with breast cancer using radiomics has been rarely explored. Purpose To establish a radiomics nomogram based on dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) for preoperatively evaluating TIL level. Study Type Retrospective. Population A total of 154 patients with breast cancer were divided into a training cohort (N = 87) and a test cohort (N = 67), who were further divided into low TIL (<50%) and high TIL (≥50%) subgroups according to the histopathological results. Field Strength/Sequence 3.0 T; axial T2‐weighted imaging (fast spin echo), diffusion‐weighted imaging (spin echo‐echo planar imaging), and the volume imaging for breast assessment DCE sequence (gradient recalled echo). Assessment A radiomics signature was developed from the training dataset and independent risk factors were selected by multivariate logistic regression to build a clinical model. A nomogram model was built by combining radiomics score and risk factors. The performance of the nomogram was assessed using calibration curves and decision curves. The area under the receiver operating characteristic (ROC) curve, accuracy, sensitivity, and specificity were calculated. Statistical Tests The least absolute shrinkage and selection operator, univariate and multivariate logistic regression analysis, t‐tests and chi‐squared tests or Fisher's exact test, Hosmer–Lemeshow test, ROC analysis, and decision curve analysis were conducted. P < 0.05 was considered statistically significant. Results The radiomics signature and nomogram model exhibited better calibration and validation performance in the training (radiomics: area under the curve [AUC] 0.86; nomogram: AUC 0.88) and test (radiomics: AUC 0.83; nomogram: AUC 0.84) datasets compared with clinical model (training: AUC 0.76; test: AUC 0.72). The decision curve demonstrated that the nomogram model exhibited better performance than the clinical model, with a threshold probability between 0.15 and 0.9. Data Conclusion The nomogram model based on preoperative MRI exhibited an excellent ability for the noninvasive evaluation of TILs in breast cancer. Level of Evidence 4 Technical Efficacy Stage 2

Background. Early detection appears to be the most effective approach to improve the overall survival of patients with hepatocellular carcinoma (HCC). We evaluated the potential performance of plasma SEPT9 methylation (mSEPT9) as a noninvasive biomarker for the diagnosis of patients with HCC. Methods. A total of 373 subjects were included, and the group consisted of 104 HCC patients, 95 with an at-risk disease, and 174 healthy controls (HC). The methylation of mSEPT9 was determined using methylation-specific fluorescence quantitative PCR. The diagnostic performance of plasma mSEPT9 for HCC was assessed in a single-blind manner. Results. The receiver operating characteristic (ROC) curve showed that plasma mSEPT9 can be used to detect and discriminate HCC with an area under the ROC curve (AUROC) of 0.961, a sensitivity of 82.7%, and specificity of 96.0% from HC. These results showed that plasma mSEPT9 had better diagnostic performance than serum alpha fetoprotein (AFP) (AUROC 0.881, sensitivity 57.7%, and specificity 98.3%). Similar results were noted in the detection of early-stage HCC. When combined with serum AFP, the sensitivity increased to 91.3% and 87.7% for the detection of HCC and early-stage HCC,respectively. Notably, the levels of plasma mSEPT9 dramatically decreased after surgery ( P = 0.001 ). Conclusions. Plasma SEPT9 methylation might serve as a useful and noninvasive biomarker for the diagnosis of HCC and can be used to evaluate the therapeutic efficacy of HCC treatment.