BackgroundHigh risk human papillomavirus (HR HPV) infects cells at the squamocolumnar junction (SCJ) of the cervix, causing cancer. Cytokeratin (CK)7 is an SCJ marker, and stains cervical neoplasia. CK19 is a binding partner of CK7 and expressed in cervical cancer. Despite this possible association between CK7/CK19 and cervical cancer, not much is known about the mechanism of CK7/CK19 involvement in HR HPV-mediated cervical carcinogenesis.MethodsWe analyzed the expression pattern of CK7, CK19, and p16 by using immunohistochemistry and HPV infection by in situ hybridization in 25 cases of high grade cervical intraepithelial neoplasia (CIN3) and in 30 cases of squamous cell carcinoma (SCC).ResultsCK19, p16, and HPV expression was positive in all CIN3 and SCC cases. CK7 expression was positive in all CIN3 cases and in 20/30 (66%) SCCs. Each protein showed diffuse or patchy staining with topographic distinction. Patchy staining of CK7 and episomal HPV DNA overlapped in the upper layer of CIN3 and central portion of an invasive nest in the SCC, whereas patchy CK19 staining and integrated HPV DNA were usually noted in the lower layer of CIN3 and the periphery of the SCC nest. The p16 staining pattern coincided with that of CK19 in a subset of SCC.ConclusionThese results suggest that CK7 may be more related with viral episomal replication and CK19 with viral integration, contributing to viral replication and malignant transformation in HR HPV infected cells. In addition, coordinate CK7/CK19 staining may be used as a valuable marker for predicting physical status of HR HPV and E7 oncoprotein level in cervical tumor.Electronic supplementary materialThe online version of this article (doi:10.1186/s13000-017-0609-4) contains supplementary material, which is available to authorized users.
Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.
We have demonstrated state-of-the-art characteristics of AlGaN/GaN-on-Si heterojunction field effect transistors (HFETs) employing dual field plates. Both gate and drain field plate lengths were optimized in order to maximize the breakdown voltage. Great care was taken not only to optimize the field plate lengths but also to develop processing technologies such as mesa-first prepassivation, a recessed ohmic contact, and a sloped gate. A breakdown voltage of 1590 V with a specific on-resistance of 1.86 m cm 2 was achieved for the gate-to-drain distance of 15 m in which the gate and drain field plate lengths were 2 and 1 m, respectively. #
The Hippo pathway is a tumor suppressive pathway regulating Yes-associated protein-TEA domain-containing sequence-specific transcription factor (YAP-TEAD) complex. VGLL (Vestigial-like) proteins are transcriptional cofactors competing with YAP for TEAD binding and interfering oncogenic activity of YAP-TEAD complex. We evaluated the expression of VGLL4, YAP, and TEAD4 and assessed their correlations with clinicopathologic factors and prognostic effects in 295 colorectal cancers. VGLL4 was positive in 164 (55.6%) cases and correlated with small tumor size, low pT classification, and absence of lymph node metastasis. YAP and TEAD4 were highly expressed in 138 (46.8%) cases and 144 (48.8%) cases, respectively, and high expressions were associated with presence of lymphovascular invasion and lymph node metastasis, or distant metastasis. VGLL4 expression was significantly correlated with low YAP expression (p < 0.001) and had significantly better overall survival than negative expression (p < 0.001). High YAP (HR, 2.108; 95% confidence interval, 1.239-3.584; p = 0.006) and TEAD4 (1.724; 1.021-2.912; p = 0.042) expressions were associated with poor overall survivals. The combined VGLL4 pos YAP low expression showed the best overall survival than other groups (p < 0.001). VGLL4 expression (0.381; 0.212-0.683; p = 0.001) and combined VGLL4 pos YAP low expression (0.227; 0.108-0.475; p < 0.001) were independent good prognostic factors in colorectal cancers. The expressions of VGLL4, YAP, and TEAD4 can be used as prognostic markers in colorectal cancer patients.
Abstract. DJ-1 and HSP90α play a significant role in the progression of various types of cancer and are known to be associated with phosphatase and tensin homolog deleted on chromosome 10 (PTEN), PI3K-p110α and pAkt, the signaling molecule proteins from the phosphatidylinositol 3-kinase (PI3K) pathway. However, the expression of these proteins and their clinical significance are not well characterized in urothelial carcinoma (UC). Immunohistochemical analysis of DJ-1, HSP90α, PTEN, pAkt and PI3K-p110α expression was performed on tumor samples from 102 patients with UC to assess the relationship between the expression of each protein and the pathological parameters. The expression of DJ-1 and HSP90α was positively correlated with the pathological stage of UC, whereas PTEN expression negatively correlated with, not only the pathological stage, but also the growth pattern and histological grade of UC. Although PI3K-p110α expression was significantly correlated with DJ-1 as well as PTEN expression in UC, PI3K-p110α expression itself failed to reveal any significant correlation with the clinicopathological para meters. In conclusion, the overexpression of DJ-1 and HSP90α, and a loss of PTEN are associated with invasive UC, and PI3K-p110α expression is correlated with DJ-1 and PTEN expression in UC.
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