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https://www.readbyqxmd.com/read/28678427/clear-cell-and-endometrioid-carcinomas-are-their-differences-attributable-to-distinct-cells-of-origin
#1
Dawn R Cochrane, Basile Tessier-Cloutier, Katherine M Lawrence, Tayyebeh Nazeran, Anthony N Karnezis, Clara Salamanca, Angela S Cheng, Jessica N McAlpine, Lien N Hoang, C Blake Gilks, David G Huntsman
Endometrial epithelium is the presumed tissue of origin for both eutopic and endometriosis-derived clear cell and endometrioid carcinomas. We had previously hypothesized that the morphological, biological and clinical differences between these carcinomas are due to histotype-specific mutations. Although some mutations and genomic landscape features are more likely to be found in one of these histotypes, we were not able to identify a single class of mutations that was exclusively present in one histotype and not the other...
July 5, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28570008/a-comparison-of-p53-and-wt1-immunohistochemical-expression-patterns-in-tubo-ovarian-high-grade-serous-carcinoma-before-and-after-neoadjuvant-chemotherapy
#2
Laura Casey, Martin Köbel, Raji Ganesan, Simone Tam, Rajeev Prasad, Steffen Böhm, Michelle Lockley, Arjun J Jeyarajah, Eleanor Brockbank, Asma Faruqi, C Blake Gilks, Naveena Singh
AIMS: Treatment of patients with tubo-ovarian high-grade serous carcinoma (HGSC) is increasingly based on diagnosis on small biopsy samples and the first surgical specimen is often post-chemotherapy. p53 and WT1 are important diagnostic markers for HGSC. The effect of neo-adjuvant chemotherapy on p53 and WT1 expression has not been widely studied. We aimed to compare p53 and WT1 expression in paired pre- and post-chemotherapy samples of HGSC. METHODS AND RESULTS: Immunohistochemistry (IHC) was carried out for p53 and WT1 on paired omental HGSC samples pre- and post-chemotherapy...
June 1, 2017: Histopathology
https://www.readbyqxmd.com/read/28489996/cancer-associated-mutations-in-endometriosis-without-cancer
#3
Michael S Anglesio, Nickolas Papadopoulos, Ayse Ayhan, Tayyebeh M Nazeran, Michaël Noë, Hugo M Horlings, Amy Lum, Siân Jones, Janine Senz, Tamer Seckin, Julie Ho, Ren-Chin Wu, Vivian Lac, Hiroshi Ogawa, Basile Tessier-Cloutier, Rami Alhassan, Amy Wang, Yuxuan Wang, Joshua D Cohen, Fontayne Wong, Adnan Hasanovic, Natasha Orr, Ming Zhang, Maria Popoli, Wyatt McMahon, Laura D Wood, Austin Mattox, Catherine Allaire, James Segars, Christina Williams, Cristian Tomasetti, Niki Boyd, Kenneth W Kinzler, C Blake Gilks, Luis Diaz, Tian-Li Wang, Bert Vogelstein, Paul J Yong, David G Huntsman, Ie-Ming Shih
BACKGROUND: Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis. METHODS: We analyzed deeply infiltrating endometriotic lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer-driver targeted sequencing (3 patients)...
May 11, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28477361/high-grade-serous-carcinoma-of-tubo-ovarian-origin-recent-developments
#4
REVIEW
Naveena Singh, W Glenn McCluggage, C Blake Gilks
Extra-uterine high-grade serous carcinoma (HGSC) accounts for most of the morbidity and mortality associated with ovarian carcinoma, and is one of the leading causes of cancer death in women. Until recently our understanding of HGSC was very limited, compared to other common cancers, and it has only been in the last 15 years that we have learned how to accurately diagnose this ovarian carcinoma histotype. Since then, however, there has been rapid progress, with identification of a precursor lesion in the fallopian tube, development of prevention strategies for both those with inherited susceptibility (Hereditary Breast and Ovarian Cancer Syndrome) and without the syndrome, and elucidation of the molecular events important in oncogenesis...
May 6, 2017: Histopathology
https://www.readbyqxmd.com/read/28436987/genomic-consequences-of-aberrant-dna-repair-mechanisms-stratify-ovarian-cancer-histotypes
#5
Yi Kan Wang, Ali Bashashati, Michael S Anglesio, Dawn R Cochrane, Diljot S Grewal, Gavin Ha, Andrew McPherson, Hugo M Horlings, Janine Senz, Leah M Prentice, Anthony N Karnezis, Daniel Lai, Mohamed R Aniba, Allen W Zhang, Karey Shumansky, Celia Siu, Adrian Wan, Melissa K McConechy, Hector Li-Chang, Alicia Tone, Diane Provencher, Manon de Ladurantaye, Hubert Fleury, Aikou Okamoto, Satoshi Yanagida, Nozomu Yanaihara, Misato Saito, Andrew J Mungall, Richard Moore, Marco A Marra, C Blake Gilks, Anne-Marie Mes-Masson, Jessica N McAlpine, Samuel Aparicio, David G Huntsman, Sohrab P Shah
We studied the whole-genome point mutation and structural variation patterns of 133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in ovarian cancer. Ab initio clustering of integrated point mutation and structural variation signatures identified seven subgroups both between and within histotypes. Prevalence of foldback inversions identified a prognostically significant HGSC group associated with inferior survival...
June 2017: Nature Genetics
https://www.readbyqxmd.com/read/28418164/molecular-subtyping-of-mammary-like-adenocarcinoma-of-the-vulva-shows-molecular-similarity-to-breast-carcinomas
#6
Basile Tessier-Cloutier, Karama Asleh-Aburaya, Varsha Shah, W Glenn McCluggage, Anna Tinker, C Blake Gilks
AIMS: Mammary-like adenocarcinoma (MLA) of the vulva is thought to be derived from vulvar mammary-like glands. We characterized a series of MLA using an immunohistochemical algorithm that identifies the major molecular subtypes of breast cancer. METHODS AND RESULTS: Seven cases of vulval MLA were stained for ER, PR, HER2, Ki-67, EGFR, CK5, nestin and INPP4b. 17 cases of vulval extramammary Paget disease (EMPD), 7 with invasion, were studied for comparison. The median age of patients with MLA was 72 years...
April 18, 2017: Histopathology
https://www.readbyqxmd.com/read/28319571/hpv-independent-differentiated-vulvar-intraepithelial-neoplasia-dvin-is-associated-with-an-aggressive-clinical-course
#7
Jessica N McAlpine, So Youn Kim, Ardalan Akbari, Sima Eshragh, Miriam Reuschenbach, Magnus von Knebel Doeberitz, Elena S Prigge, Suzanne Jordan, Naveena Singh, Dianne M Miller, C Blake Gilks
Differentiated vulvar intrapeithelial neoplasia (dVIN) is an human papillomavirus (HPV)-independent precursor of squamous cell carcinoma (SCC), and the aim of this study was to better characterize its natural history. Cases of dVIN were identified from the pathology archives. Outcomes of patients with dVIN only, without associated invasive SCC, were compared with a cohort of patients with high-grade squamous intraepithelial lesion [HSIL(VIN3)]. Eighteen patients diagnosed with dVIN with adjacent invasive SCC (SCC/dVIN) and 7 patients with dVIN only, without invasive carcinoma, were identified...
March 17, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28257152/human-papillomavirus-hpv-independent-vulvar-squamous-cell-carcinoma-has-a-worse-prognosis-than-hpv-associated-disease-a-retrospective-cohort-study
#8
Jessica N McAlpine, Samuel C Y Leung, Angela Cheng, Dianne Miller, Aline Talhouk, C Blake Gilks, Anthony N Karnezis
AIMS: Vulvar squamous cell carcinoma (VSCC) can be subdivided by human papillomavirus (HPV) status into two clinicopathological entities. Studies on the prognostic significance of HPV in VSCC are discordant. METHODS AND RESULTS: We performed a retrospective analysis of overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS) in 217 patients with VSCC. Cases were extracted from an era of more aggressive en-bloc radical dissections (1985-95) and more localized radical surgery through separate vulvar and groin excisions (1996-2005)...
March 3, 2017: Histopathology
https://www.readbyqxmd.com/read/28223274/long-term-responders-on-olaparib-maintenance-in-high-grade-serous-ovarian-cancer-clinical-and-molecular-characterization
#9
Stephanie Lheureux, Zhongwu Lai, Brian A Dougherty, Sarah Runswick, Darren Hodgson, Kirsten M Timms, Jerry S Lanchbury, Stanley B Kaye, Charlie Gourley, David D L Bowtell, Elise C Kohn, Clare L Scott, Ursula A Matulonis, Tony Panzarella, Katherine Karakasis, Julia V Burnier, Blake Gilks, Mark J O'Connor, Jane D Robertson, Jonathan Ledermann, J Carl Barrett, Tony W Ho, Amit M Oza
PURPOSE: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. EXPERIMENTAL DESIGN: A comparative molecular analysis of Study 19 (NCT00753545), a randomized Phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted...
February 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28187030/evolution-of-quality-assurance-for-clinical-immunohistochemistry-in-the-era-of-precision-medicine-part-3-technical-validation-of-immunohistochemistry-ihc-assays-in-clinical-ihc-laboratories
#10
Emina E Torlakovic, Carol C Cheung, Corrado D'Arrigo, Manfred Dietel, Glenn D Francis, C Blake Gilks, Jacqueline A Hall, Jason L Hornick, Merdol Ibrahim, Antonio Marchetti, Keith Miller, J Han van Krieken, Soren Nielsen, Paul E Swanson, Mogens Vyberg, Xiaoge Zhou, Clive R Taylor
Validation of immunohistochemistry (IHC) assays is a subject that is of great importance to clinical practice as well as basic research and clinical trials. When applied to clinical practice and focused on patient safety, validation of IHC assays creates objective evidence that IHC assays used for patient care are "fit-for-purpose." Validation of IHC assays needs to be properly informed by and modeled to assess the purpose of the IHC assay, which will further determine what sphere of validation is required, as well as the scope, type, and tier of technical validation...
March 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28182587/evolution-of-quality-assurance-for-clinical-immunohistochemistry-in-the-era-of-precision-medicine-part-2-immunohistochemistry-test-performance-characteristics
#11
Emina E Torlakovic, Carol C Cheung, Corrado D'Arrigo, Manfred Dietel, Glenn D Francis, C Blake Gilks, Jacqueline A Hall, Jason L Hornick, Merdol Ibrahim, Antonio Marchetti, Keith Miller, J Han van Krieken, Soren Nielsen, Paul E Swanson, Mogens Vyberg, Xiaoge Zhou, Clive R Taylor
All laboratory tests have test performance characteristics (TPCs), whether or not they are explicitly known to the laboratorian or the pathologist. TPCs are thus also an integral characteristic of immunohistochemistry (IHC) tests and other in situ, cell-based molecular assays such as DNA or RNA in situ hybridization or aptamer-based testing. Because of their descriptive, in situ, cell-based nature, IHC tests have a limited repertoire of appropriate TPCs. Although only a few TPCs are relevant to IHC, proper selection of informative TPCs is nonetheless essential for the development of and adherence to appropriate quality assurance measures in the IHC laboratory...
February 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28114191/frequent-mismatch-repair-protein-deficiency-in-mixed-endometrioid-and-clear-cell-carcinoma-of-the-endometrium
#12
Martin Köbel, Basile Tessier-Cloutier, Joyce Leo, Lien N Hoang, C Blake Gilks, Robert A Soslow, Deborah Delair, Colin J R Stewart, Cheng-Han Lee
Mixed endometrioid and clear cell carcinoma of the endometrium refers to a scenario in which the tumor exhibits histologic features of both endometrioid and clear cell carcinoma. We observed a tendency for these tumors to occur in a mismatch repair (MMR) protein-deficient molecular background in a prior study that examined a small cohort of mixed-type endometrial carcinomas. The aim of this study was to determine the rate of MMR protein deficiency in a larger series of endometrial mixed endometrioid and clear cell carcinomas, through a retrospective survey of MLH1, PMS2, MSH2, and MSH6 expression in such tumors at 5 tertiary centers...
January 20, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28079598/interobserver-agreement-in-endometrial-carcinoma-histotype-diagnosis-varies-depending-on-the-cancer-genome-atlas-tcga-based-molecular-subgroup
#13
Lien N Hoang, Mary A Kinloch, Joyce M Leo, Katherine Grondin, Cheng-Han Lee, Carol Ewanowich, Martin Köbel, Angela Cheng, Aline Talhouk, Melissa McConechy, David G Huntsman, Jessica N McAlpine, Robert A Soslow, C Blake Gilks
The Cancer Genome Atlas recently identified a genomic-based molecular classification of endometrial carcinomas, with 4 molecular categories: (1) ultramutated (polymerase epsilon [POLE] mutated), (2) hypermutated (microsatellite instability), (3) copy number abnormalities-low, and (4) copy number abnormalities-high. Two studies have since proposed models to classify endometrial carcinomas into 4 molecular subgroups, modeled after The Cancer Genome Atlas, using simplified and more clinically applicable surrogate methodologies...
February 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28061006/confirmation-of-promise-a-simple-genomics-based-clinical-classifier-for-endometrial-cancer
#14
Aline Talhouk, Melissa K McConechy, Samuel Leung, Winnie Yang, Amy Lum, Janine Senz, Niki Boyd, Judith Pike, Michael Anglesio, Janice S Kwon, Anthony N Karnezis, David G Huntsman, C Blake Gilks, Jessica N McAlpine
BACKGROUND: Classification of endometrial carcinomas (ECs) by morphologic features is irreproducible and imperfectly reflects tumor biology. The authors developed the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), a molecular classification system based on The Cancer Genome Atlas genomic subgroups, and sought to confirm both feasibility and prognostic ability in a new, large cohort of ECs. METHODS: Immunohistochemistry (IHC) for the presence or absence of mismatch repair (MMR) proteins (to identify MMR deficiency [MMR-D]), sequencing for polymerase-ɛ (POLE) exonuclease domain mutations (POLE EDMs), and IHC for tumor protein 53 (p53) (wild type vs null/missense mutations; p53 wt and p53 abn, respectively) were performed on 319 new EC samples...
March 1, 2017: Cancer
https://www.readbyqxmd.com/read/27960241/the-changing-landscape-of-gynaecological-cancer-diagnosis-implications-for-histopathological-practice-in-the-21st-century
#15
REVIEW
Naveena Singh, C Blake Gilks
The era of molecular medicine has led to dramatically improved understanding of the genetic events that give rise to different types of cancers. In the case of gynaecological malignancies, this has resulted in distinct shifts in how these tumours are diagnosed in routine surgical pathology practice, with an increased emphasis on accurate subtype diagnosis. This has happened across all sites in the gynaecological tract and for most cell types, but in ways that are site-specific and may appear to be subtle, as in most instances the diagnostic terminology has not changed...
January 2017: Histopathology
https://www.readbyqxmd.com/read/27941560/evolution-of-quality-assurance-for-clinical-immunohistochemistry-in-the-era-of-precision-medicine-part-4-tissue-tools-for-quality-assurance-in-immunohistochemistry
#16
Carol C Cheung, Corrado D'Arrigo, Manfred Dietel, Glenn D Francis, Regan Fulton, C Blake Gilks, Jacqueline A Hall, Jason L Hornick, Merdol Ibrahim, Antonio Marchetti, Keith Miller, J Han van Krieken, Soren Nielsen, Paul E Swanson, Clive R Taylor, Mogens Vyberg, Xiaoge Zhou, Emina E Torlakovic
The numbers of diagnostic, prognostic, and predictive immunohistochemistry (IHC) tests are increasing; the implementation and validation of new IHC tests, revalidation of existing tests, as well as the on-going need for daily quality assurance monitoring present significant challenges to clinical laboratories. There is a need for proper quality tools, specifically tissue tools that will enable laboratories to successfully carry out these processes. This paper clarifies, through the lens of laboratory tissue tools, how validation, verification, and revalidation of IHC tests can be performed in order to develop and maintain high quality "fit-for-purpose" IHC testing in the era of precision medicine...
December 9, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27922482/evolution-of-quality-assurance-for-clinical-immunohistochemistry-in-the-era-of-precision-medicine-part-1-fit-for-purpose-approach-to-classification-of-clinical-immunohistochemistry-biomarkers
#17
Carol C Cheung, Corrado D'Arrigo, Manfred Dietel, Glenn D Francis, C Blake Gilks, Jacqueline A Hall, Jason L Hornick, Merdol Ibrahim, Antonio Marchetti, Keith Miller, J Han van Krieken, Soren Nielsen, Paul E Swanson, Clive R Taylor, Mogens Vyberg, Xiaoge Zhou, Emina E Torlakovic
Technical progress in immunohistochemistry (IHC) as well as the increased utility of IHC for biomarker testing in precision medicine avails us of the opportunity to reassess clinical IHC as a laboratory test and its proper characterization as a special type of immunoassay. IHC, as used in current clinical applications, is a descriptive, qualitative, cell-based, usually nonlinear, in situ protein immunoassay, for which the readout of the results is principally performed by pathologists rather than by the instruments on which the immunoassay is performed...
January 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27885265/the-disparate-origins-of-ovarian-cancers-pathogenesis-and-prevention-strategies
#18
REVIEW
Anthony N Karnezis, Kathleen R Cho, C Blake Gilks, Celeste Leigh Pearce, David G Huntsman
Ovarian cancer is the fifth cause of cancer-related death in women and comprises a histologically and genetically broad range of tumours, including those of epithelial, sex cord-stromal and germ cell origin. Recent evidence indicates that high-grade serous ovarian carcinoma, clear cell carcinoma and endometrioid carcinoma primarily arise from tissues that are not normally present in the ovary. These histogenetic pathways are informing risk-reduction strategies for the prevention of ovarian and ovary-associated cancers and have highlighted the importance of the seemingly unique ovarian microenvironment...
January 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/27810483/tea-coffee-and-caffeinated-beverage-consumption-and-risk-of-epithelial-ovarian-cancers
#19
Andy C Y Leung, Linda S Cook, Kenneth Swenerton, Blake Gilks, Richard P Gallagher, Anthony Magliocco, Helen Steed, Martin Köbel, Jill Nation, Angela Brooks-Wilson, Nhu D Le
BACKGROUND: The risk for epithelial ovarian cancer associated with the consumption of caffeinated beverages (tea, coffee, and soft drinks) and green tea is inconclusive. However, few studies have investigated the type of caffeinated beverage or the type of tea. OBJECTIVE: We assessed consumption of tea (black/caffeinated tea and green tea separately), coffee, and caffeinated soft drinks, as well as level of consumption, and the risk for epithelial ovarian cancer and its histotypes...
December 2016: Cancer Epidemiology
https://www.readbyqxmd.com/read/27810330/foxl2-402c-g-mutation-can-be-identified-in-the-circulating-tumor-dna-of-patients-with-adult-type-granulosa-cell-tumor
#20
Anniina Färkkilä, Melissa K McConechy, Winnie Yang, Aline Talhouk, Ying Ng, Amy Lum, Ryan D Morin, Kevin Bushell, Annika Riska, Jessica N McAlpine, C Blake Gilks, Leila Unkila-Kallio, Mikko Anttonen, David G Huntsman
Adult granulosa cell tumors (AGCTs) of the ovary are molecularly characterized by the pathognomonic FOXL2 402C>G (C134W) mutation. To improve diagnostics and follow-up, we developed a specific digital droplet PCR (ddPCR) assay to detect the FOXL2 mutation in the circulating tumor DNA (ctDNA) of AGCT patients. Optimization of the ddPCR assay was performed using a TaqMan primer/probe with the RainDance RainDrop digital PCR system. The ddPCR assay was performed on circulating cell-free DNA extracted from 120 serial plasma samples collected prospectively from 35 AGCT patients...
January 2017: Journal of Molecular Diagnostics: JMD
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