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M A E Nieuwenhuis, J M Vonk, B E Himes, C Sarnowski, C Minelli, D Jarvis, E Bouzigon, D C Nickle, M Laviolette, D Sin, S T Weiss, M van den Berge, G H Koppelman, D S Postma
BACKGROUND: The severity of bronchial hyperresponsiveness (BHR) is a fundamental feature of asthma. The severity of BHR varies between asthmatics and is associated with lack of asthma control. The mechanisms underlying this trait are still unclear. This study aims to identify genes associated with BHR severity, using a genome wide association study (GWAS) on the slope of BHR in adult asthmatics. METHODS: We performed a GWAS on BHR severity in adult asthmatics from the Dutch Asthma GWAS cohort (n=650), adjusting for smoking and inhaled corticosteroid use, and verified results in 3 other cohorts...
October 6, 2016: Allergy
Worapong Singchat, Ekarat Hitakomate, Budsaba Rerkarmnuaychoke, Aorarat Suntronpong, Beiyuan Fu, Winai Bodhisuwan, Surin Peyachoknagul, Fengtang Yang, Sittichai Koontongkaew, Kornsorn Srikulnath
Genomic alteration in head and neck squamous cell carcinoma (HNSCC) was studied in two cell line pairs (HN30-HN31 and HN4-HN12) using conventional C-banding, multiplex fluorescence in situ hybridization (M-FISH), and array comparative genomic hybridization (array CGH). HN30 and HN4 were derived from primary lesions in the pharynx and base of tongue, respectively, and HN31 and HN12 were derived from lymph-node metastatic lesions belonging to the same patients. Gain of chromosome 1, 7, and 11 were shared in almost all cell lines...
2016: PloS One
Xiaoyan Liao, Parviz Haghighi, Charles S Coffey, Xiangdong Xu
Mucoepidermoid carcinoma is the most common malignant tumor of the salivary gland. The oncocytic variant of mucoepidermoid carcinoma (OMEC) is rare and a small subset shows exclusive oncocytic morphology. Here we report an OMEC case of the parotid gland in a 74-year-old woman with exclusive oncocytes and rare mucocytes. The oncocytes showed diffuse nuclear positivity with p63 immunostaining. The MAML2 translocation was present, supporting the diagnosis of OMEC. Distinguishing OMEC with exclusive oncocytes from oncocytoma and oncocytic carcinoma can be very challenging for pathologists and is critical for proper clinical management...
June 28, 2016: Rare Tumors
Liubov Kyrpychova, Denisa Kacerovska, Tomas Vanecek, Petr Grossmann, Michal Michal, Katrin Kerl, Dmitry V Kazakov
Twenty-one hidradenomas from 20 patients (13 female, 7 male) ranging in age from 18 to 87years (mean, 57.75years; median, 60years) were studied for CRTC1-MAML2 and CRTC3-MAML2 fusions to find out whether there is a correlation between the particular cell type (polyhedral eosinophilic, clear, mucinous, epidermoid, and oncocytic) and presence the above alterations. CRTC1-MAML2 fusions were detected in 10 of the 21 neoplasms (47.6%). Fluorescence in situ hybridization for MAML2 break apart was analyzable in 13 specimens and in all these specimens was positive, including 4 tumors with no demonstrable CRTC1-MAML2 fusion...
August 2016: Annals of Diagnostic Pathology
Hitomi Shinomiya, Yohei Ito D, Mie Kubo, Koichiro Yonezawa, Naoki Otsuki, Shigemichi Iwae, Hiroshi Inagaki, Ken-Ichi Nibu
In mucoepidermoid carcinoma (MEC), CRTC1-MAML2 fusion indicates a favorable prognosis. Amphiregulin (AREG), an EGFR ligand, has been shown to be a downstream target of CRTC1-MAML2 fusion, and to play a role in tumor growth and survival in CRTC1-MAML2-positive MEC cell lines. The aim of this study was to characterize the AREG and EGFR expression in the fusion positive and -negative MEC of the major salivary gland. AREG and EGFR expression was studied by immunochemistry in 33 MEC cases of the major salivary glands...
July 5, 2016: Human Pathology
Hyunseok Kang, Marietta Tan, Justin A Bishop, Siân Jones, Mark Sausen, Patrick K Ha, Nishant Agrawal
PURPOSE: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. To explore the genetic origins of MEC, we performed systematic genomic analyses of these tumors. EXPERIMENTAL DESIGN: Whole-exome sequencing and gene copy number analyses were performed for 18 primary cancers with matched normal tissue. Fluorescence in situ hybridization (FISH) was used to determine the presence or absence of the MECT1-MAML2 translocation in 17 tumors. RESULTS: TP53 was the most commonly mutated gene in MEC (28%), and mutations were found only in intermediate- and high-grade tumors...
June 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Raja R Seethala, Simion I Chiosea
No abstract text is available yet for this article.
August 2016: American Journal of Surgical Pathology
Katarzyna Lubecka, Lucinda Kurzava, Kirsty Flower, Hannah Buvala, Hao Zhang, Dorothy Teegarden, Ignacio Camarillo, Matthew Suderman, Shihuan Kuang, Ourania Andrisani, James M Flanagan, Barbara Stefanska
DNA hypomethylation was previously implicated in cancer progression and metastasis. The purpose of this study was to examine whether stilbenoids, resveratrol and pterostilbene thought to exert anticancer effects, target genes with oncogenic function for de novo methylation and silencing, leading to inactivation of related signaling pathways. Following Illumina 450K, genome-wide DNA methylation analysis reveals that stilbenoids alter DNA methylation patterns in breast cancer cells. On average, 75% of differentially methylated genes have increased methylation, and these genes are enriched for oncogenic functions, including NOTCH signaling pathway...
July 2016: Carcinogenesis
Mizuho Fujinaga, Haruna Hirose, Tomoko Saito-Shono, Kazushi Ishikawa, Hiromitsu Shimada, Yutaka Hatano, Sakuhei Fujiwara, Fumiaki Shimizu, Haruto Nishida, Kazuhiro Kawamura, Tsutomu Daa, Shigeo Yokoyama
No abstract text is available yet for this article.
August 1, 2016: European Journal of Dermatology: EJD
Claire Tingaud, Valérie Costes, Eric Frouin, Christophe Delfour, Bernard Cribier, Bernard Guillot, Vanessa Szablewski
Cutaneous clear cell hidradenoma is an uncommon benign adnexal tumor which is not supposed to metastasize, contrary to its rare malignant counterpart, hidradenocarcinoma. We report the case of a 49-year-old man, who had had a stable inguinal lymph node enlargement for 6 years. An excision was performed and revealed an intra-nodal tumor, made of large clear cells with abundant cytoplasm and round nuclei without atypia or mitosis. The immunohistochemical staining showed diffuse positivity for keratin AE1/AE3, keratin 5/6 and p63, and focal staining with keratin 7, epithelial membrane antigen (EMA) and carcinous epithelial antigen (CEA), which underlined some ductular structures...
August 2016: Journal of Cutaneous Pathology
Peter P Luk, James Wykes, Christina I Selinger, Rafael Ekmejian, Jessica Tay, Kan Gao, Timothy J Eviston, Trina Lum, Sandra A O'Toole, Jonathan R Clark, Ruta Gupta
OBJECTIVE: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy, with a proportion harboring MAML2 rearrangement. This study evaluates the diagnostic and prognostic utility of MAML2 rearrangement in MEC. STUDY DESIGN: Salivary gland malignancies at a single institution (1989-2014) were reviewed to identify MECs. Histopathologic evaluation, immunohistochemistry, and fluorescent in situ hybridization (FISH) were performed. RESULTS: Forty-one cases of MEC were identified, with mean age of 47 years and mean tumor size of 21 mm...
May 2016: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Hideoki Yokouchi, Masaki Miyazaki, Takeaki Miyamoto, Takafumi Minami, Fumio Tsuji, Kohei Murata, Kazuhito Ohishi
Mucoepidermoid carcinoma (MEC) of the lungs is a rare type of lung cancer, mainly arising from the submucosal salivary type mucous glands of the large bronchi. MEC is classified into low- and high-grade subtypes based on its cytological and histological features, and this classification correlates well with prognosis. We report the case of a 36-year-old man diagnosed after an initial episode of obstructive pneumonia. CT and bronchoscopy revealed an endobronchial mass in the right S3 bronchus and distal atelectasis...
November 2015: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Rami E Saade, Diana Bell, Joaquin Garcia, Dianna Roberts, Randal Weber
IMPORTANCE: The CRTC1/MAML2 fusion transcript, which arises from the CRTC1/MAML2 translocation, is a molecular marker unique to mucoepidermoid carcinoma (MEC), the most common malignant tumor of the salivary gland. The extent to which the transcript influences disease features and patient survival is unclear. OBJECTIVE: To determine whether the CRTC1/MAML2 fusion transcript is associated with disease stage, tumor grade, or survival outcomes in patients with MEC...
March 2016: JAMA Otolaryngology—Head & Neck Surgery
Zhen Huo, Huanwen Wu, Ji Li, Shanqing Li, Shafei Wu, Yuanyuan Liu, Yufeng Luo, Jinling Cao, Xuan Zeng, Zhiyong Liang
INTRODUCTION: Pulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm of the lung and the main salivary gland-type lung carcinoma. The aims of this study were to review the clinicopathological and immunohistochemical features of PMEC and characterize the genetic events in PMEC. METHODS: We reviewed the pathology cases in our hospital and found 34 initially diagnosed PMEC cases, 26 of which were confirmed as PMEC after excluding 8 cases of MEC-like pulmonary carcinoma...
2015: PloS One
Jie Chen, Jian-Liang Li, Zirong Chen, James D Griffin, Lizi Wu
BACKGROUND: Mucoepidermoid carcinoma (MEC) arises from multiple organs and accounts for the most common types of salivary gland malignancies. Currently, patients with unresectable and metastatic MEC have poor long-term clinical outcomes and no targeted therapies are available. The majority of MEC tumors contain a t(11;19) chromosomal translocation that fuses two genes, CRTC1 and MAML2, to generate the chimeric protein CRTC1-MAML2. CRTC1-MAML2 displays transforming activity in vitro and is required for human MEC cell growth and survival, partially due to its ability to constitutively activate CREB-mediated transcription...
2015: BMC Cancer
ChunLei Zhang, Hui Wu, YanHong Wang, YuLong Zhao, XingTang Fang, CaiFa Chen, Hong Chen
PURPOSE: Circular RNAs (circRNAs), a novel class of RNAs, perform important functions in biological processes. However, the role of circRNAs in the mammary gland remains unknown. The present study is aimed at identifying and characterizing the circRNAs expressed in the mammary gland of lactating rats. METHODS: Deep sequencing of RNase R-enriched rat lactating mammary gland samples was performed and circRNAs were predicted using a previously reported computational pipeline...
September 2015: Journal of Breast Cancer
Gaurav Goyal, Syed A Mehdi, Apar Kishor Ganti
Salivary gland tumors are a relatively rare and heterogeneous group of tumors with variable pathologic and phenotypic characteristics. The lack of clinical outcomes data and randomized controlled trials pertaining to them makes it difficult to formulate definitive treatment protocols that could help with making decisions regarding choice of therapy. Most studies involving systemic chemotherapy have not shown promising patient outcome results. With recent advances in molecular technology, however, it is now possible to identify specific genetic alterations and biomarkers as possible targets for therapeutic purposes...
October 2015: Oncology (Williston Park, NY)
Kenichiro Ishibashi, Yohei Ito, Ayako Masaki, Kana Fujii, Shintaro Beppu, Takeo Sakakibara, Hisashi Takino, Hiroshi Takase, Kei Ijichi, Kazuo Shimozato, Hiroshi Inagaki
There has been some debate as to whether a subset of metaplastic Warthin tumors (mWTs) harbor the mucoepidermoid carcinoma (MEC)-associated CRTC1-MAML2 fusion. We analyzed 15 tumors originally diagnosed as mWT (mWT-like tumors), 2 of which had concurrent MECs. We looked for the CRTC1/3-MAML2 fusion transcripts and performed immunohistochemistry for p63 and fluorescence in situ hybridization (FISH) for the MAML2 split. To localize MAML2 split-positive cells at the cellular level, whole tumor tissue sections were digitalized (whole-slide imaging [WSI])...
November 2015: American Journal of Surgical Pathology
Lisa Radkay-Gonzalez, William Faquin, Jonathan B McHugh, James S Lewis, Madalina Tuluc, Raja R Seethala
This study describes a unique subset of ciliated, human papillomavirus (HPV) related, adenosquamous carcinomas (AsqCA) of the head and neck that in contrast to most AsqCA, often show areas with lower grade cytonuclear features. They are comprised of largely non-keratinizing squamous cell carcinoma components with cystic change, gland formation, mucin production, and cilia in tumor cells. Seven cases of ciliated AsqCA were retrieved. Site distribution was as follows: palatine tonsil--3/7, base of tongue--1/7, and neck (unknown primary site)--3/7...
June 2016: Head and Neck Pathology
Diana Bell, Carol Lewis, Adel K El-Naggar, Randal S Weber
BACKGROUND: Mucoepidermoid carcinoma arises from major or minor salivary glands, making up 10% of salivary gland tumors. Intraosseous mucoepidermoid carcinomas are rare, and make up only 2% to 3% of all mucoepidermoid carcinomas. The t(11;19) and its CRTC1-MAML2 fusion gene transcript have been identified in mucoepidermoid carcinoma and are associated with a subset of mucoepidermoid carcinomas. The extent to which the transcript influences disease features and patient survival is unclear...
April 2016: Head & Neck
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