The comparison between relatively intact nanoscale extracellular vesicle derived DNA (nEV-DNA) and fragmented circulating cell free DNA (cfDNA) in mutation detection among patients with non-small cell lung cancer (NSCLC) has not been performed yet, and thus deserves investigation. Both nEV-DNA and cfDNA was obtained from 377 NSCLC patients with known EGFR mutation status and 69 controls. The respective EGFR^{E19del/T790M/L858R} mutation status was interrogated with amplification-refractory-mutation-system-based PCR assays (ARMS-PCR). Neither nEV-DNA nor cfDNA levels show a strong correlation with tumor volumes. There is no correlation between cfDNA and nEV-DNA levels either. The detection sensitivity of nEV-DNA and cfDNA using ARMS-PCR in early-stage NSCLC was 25.7% and 14.2%, respectively, with 96.6% and 91.7% specificity, respectively. In late-stage NSCLC, both nEV-DNA and cfDNA show ∼80% sensitivity and over 95% specificity. nEV-DNA is superior to cfDNA for mutation detection in early-stage NSCLC using ARMS-PCR. However, the advantages vanish in late-stage NSCLC.

Background: According to the International Multidisciplinary Classification of Lung Adenocarcinoma (LAD) by International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) in 2011, the diagnosis of LAD is changing from simple morphology into a comprehensive multidisciplinary classification. The aim of this study is to detect the expression of Notch-1 and analyze its clinicopathological or prognostic significance in different histological subtypes of Lung Adenocarcinomas (LADs). Methods: Western blot and Semi-quantitative Reverse transcription-polymerase chain reaction (RT-PCR) assays, as well as immunohisitochemistry, were performed to detect the expression of Notch-1 in LAD cells and tissue samples. Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the correlation of Notch-1 expression with clinicopathological factors and prognosis of LAD patients. Results: The expression level of Notch-1 protein in LAD cell lines or tissues was significantly lower than that in normal human bronchial epithelial cell line (16HBE) or nontumor tissues (P < 0.05). By statistical analyses, it was observed that negative Notch-1 expression was significantly associated with advanced clinical stage (P = 0.001) and lymph node metastasis (P = 0.026) in LAD patients. Also, the recurrence rate of Notch-1-positive group was higher than the Notch-1-negative group (P = 0.001), and patients with positive Notch-1 expression have a prolonged progression of overall survival (P = 0.033). More interestingly, the expression of Notch-1 protein was often observed to be negative in solid predominant adenocarcinoma (SPA) tissues, but highly expressed in papillary predominant adenocarcinoma (PPA) and micropapillary predominant adenocarcinoma (MPA) tissues. Kaplan-Meier survival analysis showed that patients with positive Notch-1 expression had a prolonged progression of overall survival compared with those with negative Notch-1 expression (P = 0.033). The median survival time of Notch-1-positive or negative patients was 64.6 months (95% CI: 31.497-97.703 months) or 36.0 months (95% CI: 12.132-59.868 months). Conclusions: Notch-1 could be used as a predictable biomarker to be detected in different pathological and histological subtypes in LAD for diagnosis or prognosis.

Objectives:. To investigate the clinicopathologic, immunophenotypic, ultrastructural, and molecular features of thyroid carcinoma showing thymus-like e

DNA polymerase iota (Pol ι) promotes invasion and metastasis of esophageal squamous cell carcinoma

Metaplastic thymoma is a rare primary thymic epithelial tumor, and its biologic behavior is uncertain. We report 7 cases of metaplastic thymoma. The spindle components of the tumor seemed to be undergoing epithelial-mesenchymal transition, which is characterized by the loss of E-cadherin expression. Epstein-Barr virus seemed not to have an etiologic role in metaplastic thymoma. No gross genetic alterations were found by using comparative genomic hybridization. The patients were alive and well in follow-up ranging from 11 to 172 months (mean, 81.7 months). The findings suggest that metaplastic thymoma has a benign clinical course. Unless the histomorphologic findings show malignant features, surgical excision alone is recommended.