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https://www.readbyqxmd.com/read/27885265/the-disparate-origins-of-ovarian-cancers-pathogenesis-and-prevention-strategies
#1
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...
November 25, 2016: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/27810483/tea-coffee-and-caffeinated-beverage-consumption-and-risk-of-epithelial-ovarian-cancers
#2
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-granulosa-cell-tumors
#3
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...
October 31, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27801755/the-fallopian-tube-origin-and-primary-site-assignment-in-extrauterine-high-grade-serous-carcinoma-findings-of-a-survey-of-pathologists-and-clinicians
#4
W Glenn McCluggage, Lynn Hirschowitz, C Blake Gilks, Nafisa Wilkinson, Naveena Singh
Accumulating recent evidence suggests that the majority of extrauterine high-grade serous carcinomas (HGSCs) do not arise from the ovary as historically accepted but from the distal, fimbrial end of the fallopian tube from a precursor known as serous tubal intraepithelial carcinoma. There has been variable acceptance of this evidence among pathologists and clinicians dealing with "ovarian" cancer and this has resulted in wide variation in the assignment of primary site between different institutions when HGSC involves >1 anatomic site...
October 31, 2016: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/27776011/uterine-serous-carcinomas-frequently-metastasize-to-the-fallopian-tube-and-can-mimic-serous-tubal-intraepithelial-carcinoma
#5
Friedrich Kommoss, Asma Faruqi, C Blake Gilks, Sarah Lamshang Leen, Naveena Singh, Nafisa Wilkinson, W Glenn McCluggage
We investigated the frequency, histopathologic, and immunohistochemical characteristics of tubal involvement in uterine serous carcinoma (USC) and aimed to clarify the relationship between "serous tubal intraepithelial carcinoma (STIC)" and USC in these cases. Cases of USC with complete tubal examination were prospectively collected and reviewed for the presence of tubal involvement. Immunohistochemical analysis for p53 and WT1 was performed on the endometrial and tubal tumor in cases with tubal involvement...
October 21, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27662035/frequent-nfib-associated-gene-rearrangement-in-adenoid-cystic-carcinoma-of-the-vulva
#6
Deyin Xing, Salwa Bakhsh, Nataliya Melnyk, Christina Isacson, Julie Ho, David G Huntsman, C Blake Gilks, Brigitte M Ronnett, Hugo M Horlings
Adenoid cystic carcinoma is a rare malignant tumor that usually arises in the major and minor salivary glands and other locations containing secretory glands, including the lower female genital tract. Lower female genital tract carcinomas with adenoid cystic differentiation can be subclassified into 2 distinct groups based on the presence or absence of high-risk HPV. Cervical mixed carcinomas with some adenoid cystic differentiation are high-risk HPV-related but pure adenoid cystic carcinomas of vulvar and cervical origin appear to be unrelated to high-risk HPV...
September 22, 2016: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/27632374/ovarian-carcinoma-diagnosis-the-clinical-impact-of-15-years-of-change
#7
Stefan Kommoss, C Blake Gilks, Andreas du Bois, Friedrich Kommoss
BACKGROUND: Until recently ovarian carcinoma was considered to be a single disease, and treatment decisions were based solely on grade and pre- and postoperative tumour burden. New insights into molecular features, treatment response, and patient demographics led the scientific community to conclude that ovarian carcinoma histotypes are different disease entities. METHODS: In 2002, the pathology specimens from patients in a clinical trial were reviewed by an experienced gynaecopathologist (pathologist A) for translational research purposes...
October 11, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27562491/concurrent-arid1a-and-arid1b-inactivation-in-endometrial-and-ovarian-dedifferentiated-carcinomas
#8
Mackenzie Coatham, Xiaodong Li, Anthony N Karnezis, Lien N Hoang, Basile Tessier-Cloutier, Bo Meng, Robert A Soslow, C Blake Gilks, David G Huntsman, Colin J R Stewart, Lynne M Postovit, Martin Köbel, Cheng-Han Lee
Dedifferentiated carcinoma of the endometrium or the ovary is an aggressive epithelial malignancy that comprises an endometrioid carcinoma together with an undifferentiated carcinoma. We recently reported that inactivation of BRG1 or INI1, core subunits of the switch/sucrose non-fermenting (SWI/SNF) complex, was the likely molecular event underlying dedifferentiation in about half of dedifferentiated carcinomas. In this study, we performed a genomic screen that included other members of the SWI/SNF complex to better delineate the molecular basis in the remainder of these tumours...
August 26, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27513074/assessment-of-ck17-as-a-marker-for-the-diagnosis-of-differentiated-vulvar-intraepithelial-neoplasia
#9
Mirna B Podoll, Naveena Singh, C Blake Gilks, Mana Moghadamfalahi, Mary Ann Sanders
Differentiated vulvar intraepithelial neoplasia (dVIN), precursor of vulvar squamous cell carcinoma, is human papilloma virus independent and often found in a background of lichen sclerosus (LS) and lichen simplex chronicus (LSC). Subtle histologic findings make the diagnosis of dVIN difficult, and, although the use of p53 and Ki-67 has been of some value, there is a need for a better immunohistochemical marker. Cytokeratin 17 (CK17), a cytoskeletal intermediate filament protein, has previously been used in the diagnosis of anogenital lesions...
August 10, 2016: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/27499902/in-depth-molecular-profiling-of-the-biphasic-components-of-uterine-carcinosarcomas
#10
Melissa K McConechy, Lien N Hoang, Michael Herman Chui, Janine Senz, Winnie Yang, Nirit Rozenberg, Robertson Mackenzie, Jessica N McAlpine, David G Huntsman, Blaise A Clarke, Cyril Blake Gilks, Cheng-Han Lee
Uterine carcinosarcoma is a clinically aggressive malignancy composed of a mix of carcinomatous and sarcomatous elements. We performed targeted next-generation sequencing of 27 uterine cancer and sarcoma genes together with immunohistochemical analyses of selected proteins in 30 uterine carcinosarcomas. This included 13 cases in which the distinct carcinoma and sarcoma components were sequenced separately and 10 cases where the metastatic tumours were analysed in addition to the primary tumours. We identified non-synonymous somatic mutations in 90% of the cases, with 27 of 30 cases (90%) harbouring TP53 alterations...
July 2015: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/27428735/classification-of-extraovarian-implants-in-patients-with-ovarian-serous-borderline-tumors-tumors-of-low-malignant-potential-based-on-clinical-outcome
#11
Jesse K McKenney, C Blake Gilks, Steve Kalloger, Teri A Longacre
The classification of extraovarian disease into invasive and noninvasive implants predicts patient outcome in patients with high-stage ovarian serous borderline tumors (tumors of low malignant potential). However, the morphologic criteria used to classify implants vary between studies. To date, there has been no large-scale study with follow-up data comparing the prognostic significance of competing criteria. Peritoneal and/or lymph node implants from 181 patients with high-stage serous borderline tumors were evaluated independently by 3 pathologists for the following 8 morphologic features: micropapillary architecture; glandular architecture; nests of epithelial cells with surrounding retraction artifact set in densely fibrotic stroma; low-power destructive tissue invasion; single eosinophilic epithelial cells within desmoplastic stroma; mitotic activity; nuclear pleomorphism; and nucleoli...
September 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27421752/molecular-classification-of-endometrial-carcinoma-on-diagnostic-specimens-is-highly-concordant-with-final-hysterectomy-earlier-prognostic-information-to-guide-treatment
#12
Aline Talhouk, Lien N Hoang, Melissa K McConechy, Quentin Nakonechny, Joyce Leo, Angela Cheng, Samuel Leung, Winnie Yang, Amy Lum, Martin Köbel, Cheng-Han Lee, Robert A Soslow, David G Huntsman, C Blake Gilks, Jessica N McAlpine
OBJECTIVE: Categorization and risk stratification of endometrial carcinomas is inadequate; histomorphologic assessment shows considerable interobserver variability, and risk of metastases and recurrence can only be derived after surgical staging. We have developed a Proactive Molecular Risk classification tool for Endometrial cancers (ProMisE) that identifies four distinct prognostic subgroups. Our objective was to assess whether molecular classification could be performed on diagnostic endometrial specimens obtained prior to surgical staging and its concordance with molecular classification performed on the subsequent hysterectomy specimen...
October 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27402148/basal-biomarkers-nestin-and-inpp4b-accurately-identify-intrinsic-subtype-in-breast-cancers-that-are-weakly-positive-for-estrogen-receptor
#13
Karama Asleh-Aburaya, Brandon S Sheffield, Zuzana Kos, Jennifer R Won, Xiu Qing Wang, Dongxia Gao, Robert Wolber, C Blake Gilks, Philip S Bernard, Stephen K L Chia, Torsten O Nielsen
AIMS: Recent evidence indicates that weakly positive immunohistochemical staining of estrogen receptor (ER) is not reliably associated with a luminal subtype, with the majority re-classified as basal-like by gene expression profile. In this study we assessed the capacity of recently-identified immunohistochemical markers of basal-like subtype not dependent on ER status- positive expression of nestin or loss of inositol polyphosphate-4-phosphatase (INPP4b)- to discriminate intrinsic subtypes, focusing on clinically-problematic cases with weak ER positivity...
July 12, 2016: Histopathology
https://www.readbyqxmd.com/read/27362902/the-chemotherapy-response-score-crs-interobserver-reproducibility-in-a-simple-and-prognostically-relevant-system-for-reporting-the-histologic-response-to-neoadjuvant-chemotherapy-in-tuboovarian-high-grade-serous-carcinoma
#14
Ian Said, Steffen Böhm, Joanne Beasley, Peter Ellery, Asma Z Faruqi, Raji Ganesan, Lynn Hirshowitz, Sharanpal Jeetle, Sarah Lam Shang Leen, W Glenn McCluggage, Jacqueline McDermott, Reena Merard, Thomas O Millner, Giorgia Trevisan, Jo Vella, C Blake Gilks, Naveena Singh
A 3-tier histopathologic scoring system, the chemotherapy response score (CRS), was previously devised for reporting the histologic response to neoadjuvant chemotherapy in interval debulking surgery specimens of stage IIIc/IV tuboovarian high-grade serous carcinoma. This has been shown to predict the outcome and offer additional information to other methods of assessing the treatment response. In the present study, the reproducibility of this scoring system was assessed by determining the interobserver agreement among reporting pathologists...
June 29, 2016: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/27297428/molecularly-defined-adult-granulosa-cell-tumor-of-the-ovary-the-clinical-phenotype
#15
Melissa K McConechy, Anniina Färkkilä, Hugo M Horlings, Aline Talhouk, Leila Unkila-Kallio, Hannah S van Meurs, Winnie Yang, Nirit Rozenberg, Noora Andersson, Katharina Zaby, Saara Bryk, Ralf Bützow, Johannes B G Halfwerk, Gerrit K J Hooijer, Marc J van de Vijver, Marrije R Buist, Gemma G Kenter, Sara Y Brucker, Bernhard Krämer, Annette Staebler, Maaike C G Bleeker, Markku Heikinheimo, Stefan Kommoss, C Blake Gilks, Mikko Anttonen, David G Huntsman
The histopathologic features of adult granulosa cell tumors (AGCTs) are relatively nonspecific, resulting in misdiagnosis of other cancers as AGCT, a problem that has not been well characterized. FOXL2 mutation testing was used to stratify 336 AGCTs from three European centers into three categories: 1) FOXL2 mutant molecularly defined AGCT (MD-AGCT) (n = 256 of 336), 2) FOXL2 wild-type AGCT (n = 17 of 336), 3) misdiagnosed other tumor types (n = 63 of 336). All statistical tests were two-sided. The overall and disease-specific survival of the misdiagnosed cases was lower than in the MD-AGCTs (P < ...
November 2016: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27241103/ovarian-cancer-in-hereditary-cancer-susceptibility-syndromes
#16
REVIEW
Quentin B Nakonechny, C Blake Gilks
Hereditary breast and ovarian cancer (HBOC) syndrome and Lynch syndrome (LS) are associated with increased risk of developing ovarian carcinoma. Patients with HBOC have a lifetime risk of up to 50% of developing high-grade serous carcinoma of tube or ovary; patients with LS have a 10% lifetime risk of developing endometrioid or clear cell carcinoma of the ovary. Testing all patients with tubo-ovarian high-grade serous carcinoma for mutations associated with HBOC syndrome, and all patients presenting with endometrioid or clear cell carcinoma of the ovary for mutations associated with LS can identify patients with undiagnosed underlying hereditary cancer susceptibility syndromes...
June 2016: Surgical Pathology Clinics
https://www.readbyqxmd.com/read/27182968/divergent-modes-of-clonal-spread-and-intraperitoneal-mixing-in-high-grade-serous-ovarian-cancer
#17
Andrew McPherson, Andrew Roth, Emma Laks, Tehmina Masud, Ali Bashashati, Allen W Zhang, Gavin Ha, Justina Biele, Damian Yap, Adrian Wan, Leah M Prentice, Jaswinder Khattra, Maia A Smith, Cydney B Nielsen, Sarah C Mullaly, Steve Kalloger, Anthony Karnezis, Karey Shumansky, Celia Siu, Jamie Rosner, Hector Li Chan, Julie Ho, Nataliya Melnyk, Janine Senz, Winnie Yang, Richard Moore, Andrew J Mungall, Marco A Marra, Alexandre Bouchard-Côté, C Blake Gilks, David G Huntsman, Jessica N McAlpine, Samuel Aparicio, Sohrab P Shah
We performed phylogenetic analysis of high-grade serous ovarian cancers (68 samples from seven patients), identifying constituent clones and quantifying their relative abundances at multiple intraperitoneal sites. Through whole-genome and single-nucleus sequencing, we identified evolutionary features including mutation loss, convergence of the structural genome and temporal activation of mutational processes that patterned clonal progression. We then determined the precise clonal mixtures comprising each tumor sample...
July 2016: Nature Genetics
https://www.readbyqxmd.com/read/27101785/immunophenotypic-features-of-dedifferentiated-endometrial-carcinoma-insights-from-brg1-ini1-deficient-tumours
#18
Lien N Hoang, Yow-Shan Lee, Anthony N Karnezis, Basile Tessier-Cloutier, Noorah Almandani, Mackenzie Coatham, C Blake Gilks, Robert A Soslow, Colin J R Stewart, Martin Köbel, Cheng-Han Lee
AIMS: Dedifferentiated endometrial carcinoma (DDEC) is defined by the presence of an undifferentiated carcinoma together with an endometrioid carcinoma. Inactivation of SMARCA4 (BRG1) and inactivation of SMARCB1 (INI1) were recently described as potential mechanisms underlying the histological dedifferentiation. The aim of this study was to characterize the immunophenotypic features of DDECs, particularly in cases with prototypical histological and molecular features (BRG1/INI1 deficiency)...
October 2016: Histopathology
https://www.readbyqxmd.com/read/27100627/loss-of-smarca4-brg1-protein-expression-by-immunohistochemistry-in-small-cell-carcinoma-of-the-ovary-hypercalcemic-type-distinguishes-these-tumors-from-their-mimics
#19
Blaise A Clarke, Leora Witkowski, Tuyet Nhung Ton Nu, Patricia A Shaw, C Blake Gilks, David Huntsman, Tony Karnezis, Neil Sebire, Janez Lamovec, Lawrence M Roth, Colin Jr Stewart, Martin Hasselblatt, William D Foulkes, W Glenn McCluggage
AIMS: Molecular interrogation of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) has revealed that it is a monogenetic tumor characterized by alteration of SMARCA4 (BRG1), a member of the Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. A large majority of cases show loss of expression of the corresponding SMARCA4/BRG1 protein. Furthermore, three cases of SCCOHT with retained SMARCA4 protein expression demonstrated loss of expression of SMARCB1/ INI1...
April 21, 2016: Histopathology
https://www.readbyqxmd.com/read/27075448/assessing-the-genetic-architecture-of-epithelial-ovarian-cancer-histological-subtypes
#20
Gabriel Cuellar-Partida, Yi Lu, Suzanne C Dixon, Peter A Fasching, Alexander Hein, Stefanie Burghaus, Matthias W Beckmann, Diether Lambrechts, Els Van Nieuwenhuysen, Ignace Vergote, Adriaan Vanderstichele, Jennifer Anne Doherty, Mary Anne Rossing, Jenny Chang-Claude, Anja Rudolph, Shan Wang-Gohrke, Marc T Goodman, Natalia Bogdanova, Thilo Dörk, Matthias Dürst, Peter Hillemanns, Ingo B Runnebaum, Natalia Antonenkova, Ralf Butzow, Arto Leminen, Heli Nevanlinna, Liisa M Pelttari, Robert P Edwards, Joseph L Kelley, Francesmary Modugno, Kirsten B Moysich, Roberta B Ness, Rikki Cannioto, Estrid Høgdall, Claus Høgdall, Allan Jensen, Graham G Giles, Fiona Bruinsma, Susanne K Kjaer, Michelle A T Hildebrandt, Dong Liang, Karen H Lu, Xifeng Wu, Maria Bisogna, Fanny Dao, Douglas A Levine, Daniel W Cramer, Kathryn L Terry, Shelley S Tworoger, Meir Stampfer, Stacey Missmer, Line Bjorge, Helga B Salvesen, Reidun K Kopperud, Katharina Bischof, Katja K H Aben, Lambertus A Kiemeney, Leon F A G Massuger, Angela Brooks-Wilson, Sara H Olson, Valerie McGuire, Joseph H Rothstein, Weiva Sieh, Alice S Whittemore, Linda S Cook, Nhu D Le, C Blake Gilks, Jacek Gronwald, Anna Jakubowska, Jan Lubiński, Tomasz Kluz, Honglin Song, Jonathan P Tyrer, Nicolas Wentzensen, Louise Brinton, Britton Trabert, Jolanta Lissowska, John R McLaughlin, Steven A Narod, Catherine Phelan, Hoda Anton-Culver, Argyrios Ziogas, Diana Eccles, Ian Campbell, Simon A Gayther, Aleksandra Gentry-Maharaj, Usha Menon, Susan J Ramus, Anna H Wu, Agnieszka Dansonka-Mieszkowska, Jolanta Kupryjanczyk, Agnieszka Timorek, Lukasz Szafron, Julie M Cunningham, Brooke L Fridley, Stacey J Winham, Elisa V Bandera, Elizabeth M Poole, Terry K Morgan, Ellen L Goode, Joellen M Schildkraut, Celeste L Pearce, Andrew Berchuck, Paul D P Pharoah, Penelope M Webb, Georgia Chenevix-Trench, Harvey A Risch, Stuart MacGregor
Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs)...
July 2016: Human Genetics
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