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Neuroendocrine tumors of the lung

Zhiyan Fu, Chunlai Zuo, Christine E Sheehan, Deepa T Patil, Jingmei Lin, Zhaohai Yang, Hwajeong Lee
Although nuclear immunostaining for paired box protein (PAX5) is widely used in practice, its cytoplasmic localization has not been evaluated. Recently we encountered cytoplasmic granular PAX5 staining in rectal well-differentiated neuroendocrine tumor (WD-NET) in the absence of nuclear staining. We investigated the specificity of this staining pattern for rectal NET (n=21) in comparison with 108 NETs, 1 WD rectal NET with elevated proliferation (WD-NET G3), and 40 poorly differentiated neuroendocrine carcinomas from the gastrointestinal and pancreatobiliary tract and liver...
March 20, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Benedito A Carneiro, Sahithi Pamarthy, Ami N Shah, Vinay Sagar, Kenji Unno, HuiYing Han, Ximing J Yang, Rubens B Costa, Rebecca J Nagy, Richard B Lanman, Timothy M Kuzel, Jeffrey S Ross, Laurie Gay, Julia A Elvin, Siraj M Ali, Massimo Cristofanilli, Young Kwang Chae, Francis J Giles, Sarki A Abdulkadir
PURPOSE: Small cell carcinoma of the prostate (SCCP) is an aggressive disease that can arise de novo or by transdifferentiation from prostate adenocarcinoma. Alterations in anaplastic lymphoma kinase (ALK) gene are involved in neuroblastoma, lung cancer, and other malignancies but its role in SCCP has not been documented. We describe a patient with refractory de novo SCCP with ALK F1174C activating mutation who obtained clinical benefit from treatment with ALK inhibitor. EXPERIMENTAL DESIGN: Next-generation sequencing (NGS) was used to analyze primary and circulating tumor DNA (ctDNA)...
March 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
William H Westra
Human papillomavirus (HPV)-related head and neck carcinoma (HNC) represents an important subgroup of head and neck cancer that is characterized by a consistent microscopic appearance and a favorable prognosis. A growing experience with HPV testing, however, has uncovered variants that deviate from the prototypic HPV-HNC with respect to morphology. While these HPV-HNCs may deviate morphologically from the prototype, they do not appear to stray far from the favorable clinical outcome assigned to HPV-positive status...
March 20, 2018: Head and Neck Pathology
Mustafa Kupeli, Resit Dogan Koseoglu
Large cell neuroendocrine carcinoma (LCNC) is a rare and aggressive cancer accounting for 3% of all lung cancers. A small percentage of LCNC called combined LCNC, can be seen in combinations with other lung tumor types. Multimodal therapy is proposed for this type of tumor but there is no any significant therapy since it is very rare tumor. This patient was a 66-year male and a heavy smoker with no symptoms of lung disease. Computed tomography core biopsy showed suspected adenocarcinoma. Right lower lobectomy was performed with mediastinal lymph node dissection via mini thoracotomy...
March 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
Kentaro Inamura
Immunohistochemistry is a widely available technique that is less challenging and can provide clinically meaningful results quickly and cost-efficiently in comparison with other techniques. In addition, immunohistochemistry allows for the evaluation of cellular localization of proteins in the context of tumor structure. In an era of precision medicine, pathologists are required to classify lung cancer into specific subtypes and assess biomarkers relevant to molecular-targeted therapies. This review summarizes the hot topics of immunohistochemistry in lung cancer, including (i) adenocarcinoma vs squamous cell carcinoma; (ii) neuroendocrine markers; (iii) ALK, ROS1, and EGFR; (iv) PD-L1 (CD274); (v) lung carcinoma vs malignant mesothelioma; and (vi) NUT carcinoma...
March 14, 2018: Cancers
Wei Zhang, Luc Girard, Yu-An Zhang, Tomohiro Haruki, Mahboubeh Papari-Zareei, Victor Stastny, Hans K Ghayee, Karel Pacak, Trudy G Oliver, John D Minna, Adi F Gazdar
Background: Small cell lung cancer (SCLC) is a deadly, high grade neuroendocrine (NE) tumor without recognized morphologic heterogeneity. However, over 30 years ago we described a SCLC subtype with "variant" morphology which did not express some NE markers and exhibited more aggressive growth. Methods: To quantitate NE properties of SCLCs, we developed a 50-gene expression-based NE score that could be applied to human SCLC tumors and cell lines, and genetically engineered mouse (GEM) models...
February 2018: Translational Lung Cancer Research
Dong-Wook Kim, Keun-Cheol Kim, Kee-Beom Kim, Colin T Dunn, Kwon-Sik Park
The discovery of recurrent alterations in genes encoding transcription regulators and chromatin modifiers is one of the most important recent developments in the study of the small cell lung cancer (SCLC) genome. With advances in models and analytical methods, the field of SCLC biology has seen remarkable progress in understanding the deregulated transcription networks linked to the tumor development and malignant progression. This review will discuss recent discoveries on the roles of RB and P53 family of tumor suppressors and MYC family of oncogenes in tumor initiation and development...
February 2018: Translational Lung Cancer Research
Mami Morita, Taku Sato, Miyuki Nomura, Yoshimi Sakamoto, Yui Inoue, Ryota Tanaka, Shigemi Ito, Koreyuki Kurosawa, Kazunori Yamaguchi, Yuki Sugiura, Hiroshi Takizaki, Yoji Yamashita, Ryuichi Katakura, Ikuro Sato, Masaaki Kawai, Yoshinori Okada, Hitomi Watanabe, Gen Kondoh, Shoko Matsumoto, Ayako Kishimoto, Miki Obata, Masaki Matsumoto, Tatsuro Fukuhara, Hozumi Motohashi, Makoto Suematsu, Masaaki Komatsu, Keiichi I Nakayama, Toshio Watanabe, Tomoyoshi Soga, Hiroshi Shima, Makoto Maemondo, Nobuhiro Tanuma
Expression of PKM2, which diverts glucose-derived carbon from catabolic to biosynthetic pathways, is a hallmark of cancer. However, PKM2 function in tumorigenesis remains controversial. Here, we show that, when expressed rather than PKM2, the PKM isoform PKM1 exhibits a tumor-promoting function in KRASG12D -induced or carcinogen-initiated mouse models or in some human cancers. Analysis of Pkm mutant mouse lines expressing specific PKM isoforms established that PKM1 boosts tumor growth cell intrinsically. PKM1 activated glucose catabolism and stimulated autophagy/mitophagy, favoring malignancy...
March 12, 2018: Cancer Cell
Yifeng Xia, Cheng Zhan, Mingxiang Feng, Mathias Leblanc, Eugene Ke, Narayana Yeddula, Inder M Verma
Small cell lung cancer (SCLC) is the most deadly subtype of lung cancer due to its dismal prognosis. We have developed a lentiviral vector-mediated SCLC mouse model and have explored the role of both the NF-κB and CREB families of transcription factors in this model. Surprisingly, induction of NF-κB activity, which promotes tumor progression in many cancer types including non-small cell lung carcinoma (NSCLC), is dispensable in SCLC. Instead, suppression of NF-κB activity in SCLC tumors moderately accelerated tumor development...
March 9, 2018: Molecular Cancer Research: MCR
Silvia Uccella, Stefano La Rosa, Marco Volante, Mauro Papotti
Neuroendocrine neoplasms (NENs) are a heterogeneous group of epithelial neoplastic proliferations that irrespective of their primary site share features of neural and endocrine differentiation including the presence of secretory granules, synaptic-like vesicles, and the ability to produce amine and/or peptide hormones. NENs encompass a wide spectrum of neoplasms ranging from well-differentiated indolent tumors to highly aggressive poorly differentiated neuroendocrine carcinomas. Most cases arise in the digestive system and in thoracic organs, i...
March 9, 2018: Endocrine Pathology
Michael S Broder, Beilei Cai, Eunice Chang, Maureen P Neary, Elya Papoyan, Al B Benson Iii
OBJECTIVE: The aim of this study was to describe real-world lung neuroendocrine tumor (NET) treatment patterns. METHODS: This study examined cytotoxic chemotherapy (CC), somatostatin analogues (SSA), targeted therapy (TT), interferon, and liver-directed therapies in 2 US claims databases. Patients ≥18 years with ≥1 inpatient or ≥2 outpatient claims for lung NET, initiating pharmacologic treatment between July 1, 2009, and June 30, 2014, were identified and followed until the end of enrollment or study end, whichever occurred first...
March 6, 2018: Oncology
Philip Carter, Costi Alifrangis, Biancastella Cereser, Pramodh Chandrasinghe, Lisa Del Bel Belluz, Thomas Herzog, Joel Levitan, Nina Moderau, Lee Schwartzberg, Neha Tabassum, Jinrui Wen, Jonathan Krell, Justin Stebbing
We evaluated the effect of tailoring treatments based on predictions informed by tumor molecular profiles across a range of cancers, using data from Caris Life Sciences. These included breast carcinoma, colorectal adenocarcinoma, female genital tract malignancy, lung non-small cell lung cancer, neuroendocrine tumors, ovarian surface epithelial carcinomas, and urinary tract cancers. Molecular profiles using mostly immunohistochemistry (IHC) and DNA sequencing for tumors from 841 patients had been previously used to recommend treatments; some physicians followed the suggestions completely while some did not...
February 6, 2018: Oncotarget
Chiachen Chen, Mary B Breslin, Michael S Lan
Neuroendocrine (NE) lung tumors account for 20% of total lung cancer cases and represent a subset of aggressive tumors with metastatic potential. High-risk NE lung cancer patients display disseminated disease, N-myc expression/amplification, and poorly differentiated tumors. In this study, we investigate the molecular mechanisms underlying a zinc-finger transcription factor, INSM1 in NE lung cancer. Our study revealed that INSM1 crosstalk with the Shh-PI3K/AKT-N-myc/Ascl1-MEK/ERK1/2 transcriptional network in NE lung cancer...
March 1, 2018: Cellular Signalling
Dimitrios Moris, Ioannis Ntanasis-Stathopoulos, Diamantis I Tsilimigras, Mohamad A Adam, Chifu Jeffrey Yang, David Harpole, Stamatios Theocharis
Primary lung neuroendocrine tumors (NETs) consist of typical and atypical carcinoids, large-cell neuroendocrine carcinomas and small-cell lung carcinomas. NETs are highly heterogeneous in histological characteristics, clinical presentation and natural history. While there are morphological and immunohistochemical criteria to establish diagnosis, there is a lack of universal consensus for prognostic factors or therapeutic targets for personalized treatment of the disease. Thus, identifying potential markers of neuroendocrine differentiation and prognostic factors remains of high importance...
March 2018: Cancer Genomics & Proteomics
Lisa Bodei, Mark S Kidd, Aviral Singh, Wouter A van der Zwan, Stefano Severi, Ignat A Drozdov, Jaroslaw Cwikla, Richard P Baum, Dik J Kwekkeboom, Giovanni Paganelli, Eric P Krenning, Irvin M Modlin
BACKGROUND: Peptide receptor radionuclide therapy (PRRT) utilizes somatostatin receptor (SSR) overexpression on neuroendocrine tumors (NET) to deliver targeted radiotherapy. Intensity of uptake at imaging is considered related to efficacy but has low sensitivity. A pretreatment strategy to determine individual PRRT response remains a key unmet need. NET transcript expression in blood integrated with tumor grade provides a PRRT predictive quotient (PPQ) which stratifies PRRT "responders" from "non-responders"...
February 26, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Rita Linhas, David Tente, Nuno China, Sara Conde, Ana Barroso
RATIONALE: Carcinoid tumors are derived from neuroendocrine cells and are most frequently found in the gastrointestinal tract and bronchopulmonary system. They are generally characterized by an indolent clinical course but may in some instances spread to regional lymph nodes or to distant sites. Subcutaneous metastases of carcinoid tumors are extremely rare; there are only few cases reported in the literature and the site of the primary tumor was mainly the gastrointestinal tract. Also, the diagnosis of this type of lesions many years after the surgical resection of the pulmonary carcinoid (PC) could be a challenge for clinicians...
January 2018: Medicine (Baltimore)
M Moeller, U Siebolts, C Wickenhauser, W Schuette
Acquired resistances to tyrosine kinase inhibitors in non-small cell lung cancer develop after 9 - 12 month. In 60 % of the cases these resistances arise because of a secondary EGFR-T790 M resistance mutation. This report is describing the case of a patient who developed parallel two different mechanisms of resistance: A T790 M resistance mutation and a transformation into a small cell neuroendocrine cancer. Under therapy with Osimertinib and chemotherapy with carboplatin and etoposide the tumor responsed partially...
February 21, 2018: Pneumologie
Eisuke Mochizuki, Shun Matsuura, Kyohei Oishi, Koichi Miyashita, Koshiro Ichijyo, Syunya Furukawa, Miyuki Nagaoka, Shinichiro Mikura, Masaru Tsukui, Naoki Koshimizu, Shogo Sakurai, Kazuhiro Asada, Toshihiro Shirai
BACKGROUND: There are few reports about the factor influencing the prognosis of high-grade neuroendocrine carcinoma. In this study, we evaluated surgical outcome of clinical stage I high-grade neuroendocrine carcinoma. METHODS: Patients who underwent curative surgery for high-grade neuroendocrine tumors of the lung in clinical stage I were included in this study. We retrospectively analyzed 27 consecutive patients. The aim of this study was to clarify the clinical course of the disease after surgery and what factors influence the prognosis...
February 17, 2018: World Journal of Surgical Oncology
J L Derks, N Leblay, S Lantuejoul, A M Dingemans, E J M Speel, L Fernandez-Cuesta
Carcinoids and large-cell neuroendocrine carcinomas (LCNEC) are rare neuroendocrine lung tumors. Here we provide an overview of the most updated data on the molecular characteristics of these diseases. Recent genomic studies showed that carcinoids generally contain a low mutational burden and few recurrently mutated genes. Most of the reported mutations occur in chromatin-remodeling genes (e.g. MEN1), and few affect genes of the PI3K-AKT-mTOR pathway. Aggressive disease has been related to chromothripsis, DNA-repair gene mutations, loss of OTP/CD44, and upregulation of RET gene expression...
February 14, 2018: Journal of Thoracic Oncology
Hyun S Kim, Walid L Shaib, Chao Zhang, Ganji Purnachandra Nagaraju, Christina Wu, Olatunji B Alese, Zhengjia Chen, Edith Brutcher, Meredith Renfroe, Bassel F El-Rayes
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2...
February 16, 2018: Cancer
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