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Blake gilks

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https://www.readbyqxmd.com/read/28319571/hpv-independent-differentiated-vulvar-intraepithelial-neoplasia-dvin-is-associated-with-an-aggressive-clinical-course
#1
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/hpv-independent-vulvar-squamous-cell-carcinoma-has-a-worse-prognosis-than-hpv-associated-disease-a-retrospective-cohort-study
#2
Jessica N McAlpine, Samuel Leung, Angela Cheng, Dianne Miller, Aline Talhouk, C Blake Gilks, Anthony N Karnezis
BACKGROUND: Vulvar squamous cell carcinoma (VSCC) can be subdivided by HPV status into two clinicopathological entities. Studies on the prognostic significance of HPV in VSCC are discordant. METHODS: 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 (1985-1995) 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
#3
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
#4
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...
February 9, 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
#5
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
#6
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
#7
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
#8
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...
January 6, 2017: Cancer
https://www.readbyqxmd.com/read/27960241/the-changing-landscape-of-gynaecological-cancer-diagnosis-implications-for-histopathological-practice-in-the-21st-century
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
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
#15
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
#16
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...
February 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27662035/frequent-nfib-associated-gene-rearrangement-in-adenoid-cystic-carcinoma-of-the-vulva
#17
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
#18
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
#19
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
#20
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
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