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Glioma has a specific CpG island methylator phenotype (G⁃CIMP), which is closely related to isocitrate dehydrogenase (IDH) mutation. A hypermutation is present at recurrence in temozolomide⁃treated gliomas, and O6⁃methylguanine⁃DNA methyltransferase (MGMT) promoter methylation levels can help predict the risk of hypermutation to inform clinical decision. Whole genome DNA methylation analysis has become an effective auxiliary method for the classification of central nervous system tumors. This article reviews the research progress of DNA methylation analysis in glioma and discusses its clinical significance.

Objective A retrospective analysis of the clinical and pathological features of an anaplastic large cell lymphoma (ALCL) with cavernous sinus syndrome as its first symptom. Methods and Results A 35-year-old woman had head and facial pain for a month, diplopia for 7 d, right eyelid drooped for 4 d. Head MRI showed abnormal signals in right cavernous sinus, and pituitary adenoma or carvernous sinus syndrome were considered. Partial tumor resection was performed after hormone therapy was failed. Histological manifestations revealed that the tumor cells were diffuse and heterogeneous with abundant and pink stained cytoplasm, round, oval, irregular or kidney-shaped nuclei. Immunohistochemical staining showed that CD30 and CD56 were positive on the membrane, and epithelial membrane antigen (EMA) was positive on membrane and cytoplasm, and anaplastic lymphoma kinase (ALK) was negative. Ki-67 labeling index was 80%. Unfortunately, this patient died 3 weeks later after the operation, because of severe illness and intolerance to radiotherapy and chemotherapy. Conclusions The diagnosis of ALCL should be considered when cavernous sinus syndrome as the clinical symptom, and pathological examination should be performed if necessary. It should be differentiated from some tumors, such as undifferentiated non - keratinizing nasopharyngeal carcinoma, germinoma, plasmablastic lymphoma, malignant melanoma and Hodgkin's lymphoma (HL). [ABSTRACT FROM AUTHOR]

Background Accurate diagnosis of papillary thyroid microcarcinoma (PTMC) is important for further management. Ultrasound (US) is the most frequently used imaging modality for PTMC. Purpose To evaluate the diagnostic value of conventional US, contrast-enhanced ultrasound (CEUS) and real-time elastography (RTE) for patients with PTMC. Material and Methods In total, 135 patients with subcentimeter thyroid nodules who underwent conventional US, CEUS, and RTE before surgery were enrolled. A multivariate logistic regression analysis was performed to assess the independent predictors of PTMC. The diagnostic performances of conventional US, CEUS, and RTE were evaluated with a receiver operating characteristic (ROC) curve analysis. Results A taller-than-wide shape was identified as the strongest predictor of PTMC (odds ratio [OR], 25.21), followed by heterogeneous enhancement (OR, 24.03), marked hypoechogenicity (OR, 21.71), poorly defined margin (OR, 5.51), strain ratio (OR, 2.59), and age (OR, 0.92; all P values < 0.05). Heterogeneous enhancement on CEUS showed the highest positive predictive value (PPV; 88.0%) and an accuracy of 83.7%. A logistic regression model was created to predict PTMC using conventional US, CEUS, and RTE. The area under the ROC curve was 0.97, with a sensitivity of 88.6% and a specificity of 94.6%. Conclusion Conventional US combined with CEUS and RTE can improve the diagnostic accuracy of PTMC. [ABSTRACT FROM AUTHOR]

Primary giant-cell tumors rarely arise in the common bile duct. We herein report a case of primary giant-cell tumor of the common bile duct. The patient was an 81-year-old male who was diagnosed with a well-defined 1.2-cm mass projecting into the lumen of the middle common bile duct. Excision of the gallbladder and extrahepatic bile duct and a Roux-en-Y cholangiojejunostomy were performed. Histologically, the tumor had no association with carcinomas of epithelial origin and was similar to giant-cell tumors of the bone. The tumor consisted of a mixture of mononuclear and multinucleated osteoclast-like giant cells. The mononuclear cells showed no atypical features, and their nuclei were similar to those of the multinucleated giant cells. CD68 was expressed on the mononuclear and multinucleated osteoclast-like giant cells, whereas CD163 immunoreactivity was restricted to the mononuclear cells. Six months after the operation, the patient was still alive and had no recurrence. The interest of this case lies in the rarity of this entity, the difficulty of preoperative diagnosis, and this tumor's possible confusion with other malignant tumors.

Dynamin 2 (Dyn2) is essential for intracellular vesicle formation and trafficking, cytokinesis, and receptor endocytosis. In this study, we investigated the implication of Dyn2 as a prognostic marker and therapeutic target for progressive prostate cancer (PCA). We evaluated Dyn2 protein expression by immunohistochemistry in two cohorts: men with localized PCA treated by retropubic radical prostatectomy (n = 226), and men with advanced/castrate-resistant PCA (CRPC) treated by transurethral resection of prostate (TURP) (n = 253). The role of Dyn2 in cell invasiveness was assessed by in vitro and in vivo experiments using androgen-responsive and refractory PCA preclinical models. Dyn2 expression was significantly increased across advanced stages of PCA compared to benign prostate tissue (P < 0.0001). In the CRPC cohort, high Dyn2 was associated with higher Gleason score (P = 0.004) and marginally with cancer-specific mortality (P = 0.052). In preclinical models, Dyn2 gene silencing significantly reduced cell migration and invasion in vitro, as well as tumor size and lymph node metastases in vivo. In isolated PCA cells, Dyn2 was found to regulate focal adhesion turnover, which is critical for cell migration; this mechanism requires full Dyn2 compared to mutants deficient in GTPase activity. In conclusion, Dyn2 overexpression is associated with neoplastic prostate epithelium and is associated with poor prognosis. Inhibition of Dyn2 prevents cell invasiveness in androgen-responsive and -refractory PCA models, supporting the potential benefit of Dyn2 to serve as a therapeutic target for advanced PCA., (© 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To investigate the expression of annexin I in esophageal squamous cell carcinoma (SCC) and carcinomas of other histological types in order to analyze the correlation between the expression of annexin I and carcinogenesis., Methods: First, a set of tissue microarray was established, which consisted of SCC from the esophagus (208 cases), lung, larynx, cervix, and external genital organs; adenocarcinomas from the lung, stomach, colon and rectum, liver, pancreas, breast, thyroid and kidney with 30 cases in each group, meanwhile, the corresponding normal tissue was also obtained for control. Immunohistochemistry was used to detect the expression of annexin I in different types of carcinomas and the corresponding normal controls from different organs. The correlation between the expression of annexin I and the clinicopathological feature was analyzed and compared, which included age, gender, differentiation grade and lymph node metastasis., Results: It was found that the expression of annexin I was decreased in esophageal SCC, when compared with normal esophageal squamous epithelia (P < 0.001), the similarity was also found in SCC of the lung, larynx and cervix. However, though negative in normal epidermis, annexin I expression was detected in some cases with SCC from external genital organs. Annexin I was found to be overexpressed in adenocarcinomas of the lung, stomach, colon and rectum, liver, pancreas, breast, thyroid and kidney, particularly very strong expression of annexin I was seen in lung adenocarcinoma, uterine endometrioid adenocarcinoma and ovarian serous adenocarcinoma. Interestingly, it was found to be positive in all thyroid papillary carcinomas, but negative in all normal thyroid glands. However, annexin I expression was found to be negative in all hepatocellular carcinoma and normal hepatocytes; and it was only detected in myoepithelium of normal breast tissue, but not in ductal luminal cells, and rarely in infiltrating ductal adenocarcinoma. In SCC, annexin I expression was stronger in well differentiated ones than that in the poorly differentiated ones. However, contrasting with SCC, in the adenocarcinomas from different organs, annexin I expression was much stronger in poorly differentiated ones than that in the well differentiate ones, especially in the adenocarcinomas from stomach, colon and rectum, pancreas, ovarian and kidney., Conclusion: Annexin I expression is quite different among different types of carcinomas, and is correlated with histopathological type and differentiation grade. Further study is needed to investigate its role in the carcinogenesis.

Objective: To study the immunohistochemical expression of OCT4, CD117 and CD30 in germ cell tumors and to assess their diagnostic value., Methods: Immunohistochemical study for OCT4 was performed on formalin-fixed, paraffin-embedded tissues of 63 cases of germ cell tumors, including seminoma (21), dysgerminoma (7), germinoma (8), embryonal carcinoma (8), yolk sac tumor (6), mature teratoma (10) and immature teratoma (3), as well as 25 cases of non-germ cell tumors, including granulosa cell tumor (8), clear cell adenocarcinoma (4), Leydig's cell tumor (5), diffuse large B-cell lymphoma (4) and malignant melanoma (4). Besides, the expression of CD117 and CD30 in all germ cell tumors was studied., Results: All cases of seminoma and germinoma, 6/7 cases of dysgerminoma and 7/8 cases of embryonal carcinoma were positive for OCT4, with strong nuclear staining. All other germ cell tumors and non-germ cell tumors were negative for OCT4, except for 1 case of yolk sac tumor and 1 case of clear cell adenocarcinoma which showed weak staining. Positive membranous expression of CD117 was demonstrated in 19/21(90.5%) seminoma, 5/7 dysgerminoma and 7/8 germinoma. Focal weak membranous staining was also noted in 1 case of yolk sac tumor. The melanocytes in teratoma were also positive for CD117. All cases of embryonal carcinoma were negative. On the other hand, positive membranous expression of CD30 were demonstrated in 6/8 embryonal carcinoma. One case of germinoma and 1 case of yolk sac tumor showed weak cytoplasmic positivity. All cases of seminoma and dysgerminoma, 7/8 germinoma and all cases of teratoma were negative for CD30., Conclusions: OCT4 is a sensitive and relatively specific marker for diagnosing seminoma, dysgerminoma, germinoma and embryonal carcinoma. CD117 and CD30 immunostains, when used in combination, represent valuable tools for distinguishing embryonal carcinoma and seminoma, dysgerminoma, germinoma.

Aim: To investigate biogenesis and intracellular localizations of clusterin to elucidate the potential molecular mechanisms implicated in tumorigenesis of esophageal mucosa., Methods: Semi-quantitative RT-PCR for multi-region alteration analysis, Western blot for different transcriptional forms and immunohistochemical staining for intracellular localizations of clusterin were carried out in both tissues and cell lines of ESCC., Results: The N-terminal deletions of the clusterin gene and the appearance of a 50-53 ku nuclear clusterin, an uncleaved, nonglycosylated, and disulfide-linked isoform, were the major alterations in cancer cells of esophagus. Naturally the 40 ku clusterin was located in the connective tissue of the lamina propria of epithelial mucosa and right under the basal membrane of epithelia, but it was disappeared in stromal mucosa of esophagus and the pre-matured clusterin was found positive in cancerous epithelia., Conclusion: The N-terminal deletion of clusterin may be essential for its alterations of biogenesis in ESCC.