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Alk translocation

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https://www.readbyqxmd.com/read/29774061/immunotherapy-in-non-metastatic-non-small-cell-lung-cancer-can-the-benefits-of-stage-iv-therapy-be-translated-into-earlier-stages
#1
REVIEW
Griet Deslypere, Dorothée Gullentops, Els Wauters, Johan Vansteenkiste
Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR ) activating mutations or anaplastic lymphoma kinase ( ALK ) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29741520/alk-immunohistochemistry-is-highly-sensitive-and-specific-for-the-detection-of-alk-translocated-lung-adenocarcinomas-lessons-from-an-audit-of-lung-cancer-molecular-testing
#2
Y C Kheng, K Walsh, L Williams, W A Wallace, D J Harrison, A Oniscu
Background The approval of novel targeted treatments for epidermal growth factor receptor (EGFR)-positive and anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer has led to the increased requirement for mutation testing. Results We report our experience of ALK testing with immunohistochemistry (IHC) and fluorescence in-situ hybridisation (FISH) and present the prevalence of EGFR, Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) and ALK mutations. From January 2011 to May 2014, we found mutation rates of EGFR, KRAS and ALK to be 10...
March 2018: Journal of the Royal College of Physicians of Edinburgh
https://www.readbyqxmd.com/read/29720004/pulmonary-adenocarcinoma-mimicking-desquamative-interstitial-pneumonia-report-of-2-cases-with-genetic-analysis
#3
Masashi Miyaoka, Kazuhito Hatanaka, Masayuki Iwazaki, Naoya Nakamura
We report 2 cases of pulmonary adenocarcinoma mimicking desquamative interstitial pneumonia (DIP) with genetic analysis occurring in a 74-year-old woman and a 76-year-old woman. In both cases, the tumor was mainly composed of discohesive tumor cells, which filled and floated in the alveolar space in a DIP-like pattern. The tumor cells had abnormally large round to oval nuclei with fine chromatin and relatively abundant eosinophilic cytoplasm lacking pigmentation. Immunohistochemically, tumor cells in both cases were positive for CK7, TTF-1, napsin A, E-cadherin, β-catenin, and PD-L1 (one case had high expression and the other had low expression), and negative for CK5/6, CK20, p40, and ALK...
May 1, 2018: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29690664/-clinicopathologic-features-of-gastric-plexiform-fibromyxoma
#4
G M Hu, H P Chen, Q Y Liu, X C Shi, H F Wu, Y K Feng, J L Ren, C F Wang
Objective: To analyse the clinicopathologic features of gastric plexiform fibromyxoma (PF) including diagnosis, differential diagnosis, immunohistochemistry and molecular pathology. Methods: Eight cases of PF were collected from June 2006 to June 2017 at the Second Affiliated Hospital of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University. The clinicopathologic findings of eight cases of PF were retrospectively analyzed, and immunohistochemistry (EnVision method) and molecular detection of glioma-associated oncogene homologue 1 (GLI1) gene translocation were performed...
April 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29683819/primary-and-metastatic-melanoma-with-ntrk-fusions
#5
Cecilia Lezcano, Alexander N Shoushtari, Charlotte Ariyan, Travis J Hollmann, Klaus J Busam
A number of oncogenic driver mutations have been identified in melanocytic nevi and melanoma, but translocations also play a role in tumorigenesis and provide potential therapeutic targets for malignant lesions. Various translocations, such as those involving the anaplastic lymphoma kinase (ALK), neurotrophic tropomyosin receptor kinase 1 (NTRK1), and NTRK3 have been reported in spitzoid melanocytic neoplasms leading to kinase-fusion proteins that result in immunohistochemically detectable ALK or NTRK expression...
April 20, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29661733/analysis-of-eml4-alk-rearrangement-in-non-small-cell-lung-cancer-in-argentina
#6
María Verzura, Emilio Batagelj, Claudia Bagnes, Claudio Martin, Diego Enrico, Eduardo Richardet, Paola De la Iglesia
INTRODUCTION: Identification of EML4-ALK rearrangement by FISH test has become standard in advanced NSCLC patients. There is limited information about the prevalence and clinical characteristics of ALK translocation in Latin America. The aim of our study was to evaluate this lung cancer subtype features in Argentinian patients and the factibility of FISH test with different methods used for obtaining tissue samples. METHODS: Between August 2014 and February 2017, 183 non-squamous NSCLC patients were prospectively enrolled from five Argentinian institutions...
February 26, 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29623743/immunoexpression-of-bap1-ros1-and-alk-in-spitzoid-melanocytic-tumors
#7
Leonardo Cardili, Cristiano Ribeiro Viana, Andressa Germano, Mariana Fernandes, Denise Barcellos, Gilles Landman
BACKGROUND: Spitzoid tumors are a heterogeneous group of melanocytic neoplasms that frequently imposes diagnostic difficulties. Lately, several advances in molecular biology afforded significant discoveries on the pathogenesis of these tumors. BAP1 (BRCA-1 associated protein-1) inactivation and anomalous expression of kinase translocation-related proteins are among the main criteria launched by new classification proposals. Our aim was to systematically assess the immunoexpression of BAP1, ROS1 (receptor tyrosine kinase c-Ros oncogene 1), and ALK (anaplastic lymphoma receptor tyrosine kinase) proteins in an unpublished series of spitzoid tumors...
April 1, 2018: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29617304/the-pathological-spectrum-of-systemic-anaplastic-large-cell-lymphoma-alcl
#8
REVIEW
Ivonne A Montes-Mojarro, Julia Steinhilber, Irina Bonzheim, Leticia Quintanilla-Martinez, Falko Fend
Anaplastic large cell lymphoma (ALCL) represents a group of malignant T-cell lymphoproliferations that share morphological and immunophenotypical features, namely strong CD30 expression and variable loss of T-cell markers, but differ in clinical presentation and prognosis. The recognition of anaplastic lymphoma kinase (ALK) fusion proteins as a result of chromosomal translocations or inversions was the starting point for the distinction of different subgroups of ALCL. According to their distinct clinical settings and molecular findings, the 2016 revised World Health Organization (WHO) classification recognizes four different entities: systemic ALK-positive ALCL (ALK+ ALCL), systemic ALK-negative ALCL (ALK− ALCL), primary cutaneous ALCL (pC-ALCL), and breast implant-associated ALCL (BI-ALCL), the latter included as a provisional entity...
April 4, 2018: Cancers
https://www.readbyqxmd.com/read/29610932/eml4-alk-rearrangement-in-squamous-cell-carcinoma-shows-significant-response-to-anti-alk-inhibitor-drugs-crizotinib-and-alectinib
#9
Thomas Huang, Brigitte J Engelmann, Rachael M Morgan, Kimberly J Absher, Jill M Kolesar, John L Villano
EML4-ALK alterations are more common in adenocarcinomas and are rarely found in squamous cell histology. In documented cases, the majority of EML4-ALK translocations are identified in squamous cell histology and occur in patients with no or light smoking history. We report an EML4-ALK4 translocation in a 50-year-old patient with squamous cell carcinoma and an 18 pack-year smoking history. The patient had a near complete response in the CNS to alectinib treatment. Our observation suggests that EML4-ALK genomic testing may be clinically useful in patients with heavy smoking history...
April 2, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29600072/aberrant-status-and-clinicopathologic-characteristic-associations-of-11-target-genes-in-1-321-chinese-patients-with-lung-adenocarcinoma
#10
Mengnan Zhao, Cheng Zhan, Ming Li, Xiaodong Yang, Xinyu Yang, Yong Zhang, Miao Lin, Yifeng Xia, Mingxiang Feng, Qun Wang
Background: The aberrant status of target genes and their associations with clinicopathologic characteristics are still unclear in primary lung adenocarcinoma. Methods: The common mutations and translocations of nine target genes were evaluated in 1,247 specimens of surgically-resected primary lung adenocarcinoma. Immunohistochemistry was used to analyze the expressions of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) in 731 specimens. The frequency of the aberrations and their associations with clinicopathologic characteristics were analyzed...
January 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29581862/doxorubicin-induced-loss-of-dna-topoisomerase-ii-and-dnmt1-dependent-suppression-of-mir-125b-induces-chemoresistance-in-alk-positive-cells
#11
Annabelle Congras, Nina Caillet, Nouritza Torossian, Cathy Quelen, Camille Daugrois, Pierre Brousset, Laurence Lamant, Fabienne Meggetto, Coralie Hoareau-Aveilla
Systemic anaplastic large-cell lymphoma (ALCL) is a childhood T cell neoplasm defined by the presence or absence of translocations that lead to the ectopic expression of anaplastic lymphoma kinase (ALK), with nucleophosmin-ALK (NPM-ALK) fusions being the most common. Polychemotherapy involving doxorubicin is the standard first-line treatment but for the 25 to 35% of patients who relapse and develop resistance the prognosis remains poor. We studied the potential role of the microRNA miR-125b in the development of resistance to doxorubicin in NPM-ALK(+) ALCL...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29549897/detection-of-ret-rearranged-during-transfection-variants-and-their-downstream-signal-molecules-in-ret-rearranged-lung-adenocarcinoma-patients
#12
Jeong-Oh Kim, Jung-Young Shin, Min Young Kim, Kyoung Hwa Son, Chan Kwon Jung, Tae-Jung Kim, Su Young Kim, Jae Kil Park, Sook Whan Sung, Sang Ju Bae, Hyun Jung Min, Jin-Hyoung Kang
BACKGROUND: We screened resected tumor tissues from patients with lung cancer for EGFR mutations, ALK rearrangements, and rearranged during transfection (RET) gene variants (including RET rearrangements and the Kinesin Family Member 5B (KIF5B)-RET fusion gene) using various methods including reverse transcription polymerase chain reaction (RT-PCR), transcript assays, fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). We also examined the protein expression of associated downstream signaling molecules to assess the effect of these variants on patient outcome...
March 2018: Surgical Oncology
https://www.readbyqxmd.com/read/29518553/phase-1-2-study-of-the-safety-and-tolerability-of-nivolumab-plus-crizotinib-for-the-first-line-treatment-of-anaplastic-lymphoma-kinase-translocation-positive-advanced-non-small-cell-lung-cancer-checkmate-370
#13
David R Spigel, Craig Reynolds, David Waterhouse, Edward B Garon, Jason Chandler, Sunil Babu, Paul Thurmes, Alexander Spira, Robert Jotte, Jin Zhu, Wen Hong Lin, George Blumenschein
INTRODUCTION: Crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is a first-line treatment for ALK translocation-positive advanced non-small cell lung cancer (NSCLC); however, patients eventually progress. Immunotherapies, including the programmed death-1 inhibitor nivolumab, have resulted in durable responses and long-term overall survival in patients with NSCLC. We hypothesized that combining targeted therapy with immunotherapy could result in more patients with responses and/or more durable responses...
May 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29510549/the-role-of-oncogenic-tyrosine-kinase-npm-alk-in-genomic-instability
#14
REVIEW
Cosimo Lobello, Vasilis Bikos, Andrea Janikova, Sarka Pospisilova
Genomic stability is crucial for cell life and transmitting genetic material is one of the primary tasks of the cell. The cell needs to be able to recognize any possible error and quickly repair it, and thus, cells have developed several mechanisms to detect DNA damage and promote repair during evolution. The DNA damage response (DDR) and DNA repair pathways ensure the control of possible errors that could impair the duplication of genetic information and introduce variants in the DNA. Endogenous and exogenous factors compromise genomic stability and cause dysregulation in the DDR and DNA repair pathways...
March 5, 2018: Cancers
https://www.readbyqxmd.com/read/29507487/standardizing-biomarker-testing-for-canadian-patients-with-advanced-lung-cancer
#15
B Melosky, N Blais, P Cheema, C Couture, R Juergens, S Kamel-Reid, M-S Tsao, P Wheatley-Price, Z Xu, D N Ionescu
Background: The development and approval of both targeted and immune therapies for patients with advanced non-small cell lung cancer (nsclc) has significantly improved patient survival rates and quality of life. Biomarker testing for patients newly diagnosed with nsclc, as well as for patients progressing after treatment with epidermal growth factor receptor ( EGFR ) inhibitors, is the standard of care in Canada and many parts of the world. Methods: A group of thoracic oncology experts in the field of thoracic oncology met to describe the standard for biomarker testing for lung cancer in the Canadian context, focusing on evidence-based recommendations for standard-of-care testing for EGFR , anaplastic lymphoma kinase ( ALK ), ROS1 , BRAF V600 and programmed death-ligand (PD-L1) at the time of diagnosis of advanced disease and EGFR T790M upon progression...
February 2018: Current Oncology
https://www.readbyqxmd.com/read/29487011/analysis-of-the-proliferative-activity-in-lung-adenocarcinomas-with-specific-driver-mutations
#16
Mark Kriegsmann, Alexander Harms, Daniel Kazdal, Sebastian Fischer, Albrecht Stenzinger, Jonas Leichsenring, Roland Penzel, Rémi Longuespée, Katharina Kriegsmann, Thomas Muley, Seyer Safi, Arne Warth
In the last decade it became evident that many lung adenocarcinomas (ADC) harbor key genetic alterations such as KRAS, EGFR or BRAF mutations as well as rearrangements of ROS1 or ALK that drive these tumors. In the present study we investigated whether different driver mutations of ADC result in different proliferation rates, which might have clinical impact, including resistance to therapy, recurrence and prognosis. We analyzed the proliferation index (PI) on full slides of surgically resected ADC (n = 230) with known genetic aberrations by means of immunohistochemistry and subsequent digital image analysis and correlated the results with clinicopathological variables including overall (OS) and disease free survival (DFS)...
March 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29473341/expression-and-copy-number-gains-of-the-ret-gene-in-631-early-and-mid-stage-non-small-cell-lung-cancer-cases
#17
Ling Tan, Yerong Hu, Yongguang Tao, Bin Wang, Jun Xiao, Zhenjie Tang, Ting Lu, Hao Tang
BACKGROUND: To identify whether RET is a potential target for NSCLC treatment, we examined the status of the RET gene in 631 early and mid stage NSCLC cases from south central China. METHODS: RET expression was identified by Western blot. RET-positive expression samples were verified by immunohistochemistry. RET gene mutation, copy number variation, and rearrangement were analyzed by DNA Sanger sequencing, TaqMan copy number assays, and reverse transcription-PCR...
April 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29455653/novel-targeted-therapies-and-immunotherapy-for-advanced-thyroid-cancers
#18
REVIEW
George E Naoum, Michael Morkos, Brian Kim, Waleed Arafat
Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29429162/-pulmonary-microcystic-fibromyxoma-report-of-a-case-with-review-of-literature
#19
REVIEW
Q X Gong, H Li, Z H Zhang, Q H Fan
Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of pulmonary microcystic fibromyxoma. Methods: In March 2014, at the First Affiliated Hospital to Nanjing Medical University a 58-year-old female patient of pulmonary microcystic fibromyxoma was collected. The clinicopathologic, immunohistochemical and genetic profile of a case of pulmonary microcystic fibromyxoma were studied, and the relevant literature reviewed. Results: The patient was a 58-year-old female who presented with cough and sputum for 1 month...
February 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29413048/distinct-clinicopathologic-features-genomic-characteristics-and-survival-of-central-and-peripheral-pulmonary-large-cell-neuroendocrine-carcinoma-from-different-origin-cells
#20
Fei Zhou, Likun Hou, Ting Ding, Quanming Song, Xiaoxia Chen, Chunxia Su, Wei Li, Guanghui Gao, Shengxiang Ren, Fengying Wu, Jiang Fan, Chunyan Wu, Jie Zhang, Caicun Zhou
BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) represents a rare entity in lung cancer with dismal prognosis. In the present study, we investigated whether there are significant differences between central and peripheral tumors of LCNEC, in terms of clinicopathologic features, genomic profiles, and survival. METHODS AND MATERIALS: A total of 126 cases of LCNEC were included. The tumors with invasion of the segmental and/or lobar bronchus were classified as central LCNEC and those without as peripheral LCNEC...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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