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https://www.readbyqxmd.com/read/29754820/interfaces-of-malignant-and-immunologic-clonal-dynamics-in-ovarian-cancer
#1
Allen W Zhang, Andrew McPherson, Katy Milne, David R Kroeger, Phineas T Hamilton, Alex Miranda, Tyler Funnell, Nicole Little, Camila P E de Souza, Sonya Laan, Stacey LeDoux, Dawn R Cochrane, Jamie L P Lim, Winnie Yang, Andrew Roth, Maia A Smith, Julie Ho, Kane Tse, Thomas Zeng, Inna Shlafman, Michael R Mayo, Richard Moore, Henrik Failmezger, Andreas Heindl, Yi Kan Wang, Ali Bashashati, Diljot S Grewal, Scott D Brown, Daniel Lai, Adrian N C Wan, Cydney B Nielsen, Curtis Huebner, Basile Tessier-Cloutier, Michael S Anglesio, Alexandre Bouchard-Côté, Yinyin Yuan, Wyeth W Wasserman, C Blake Gilks, Anthony N Karnezis, Samuel Aparicio, Jessica N McAlpine, David G Huntsman, Robert A Holt, Brad H Nelson, Sohrab P Shah
High-grade serous ovarian cancer (HGSC) exhibits extensive malignant clonal diversity with widespread but non-random patterns of disease dissemination. We investigated whether local immune microenvironment factors shape tumor progression properties at the interface of tumor-infiltrating lymphocytes (TILs) and cancer cells. Through multi-region study of 212 samples from 38 patients with whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T and B cell receptor sequencing, we identified three immunologic subtypes across samples and extensive within-patient diversity...
May 7, 2018: Cell
https://www.readbyqxmd.com/read/29660837/dicer1-hotspot-mutations-in-ovarian-gynandroblastoma
#2
Yemin Wang, Anthony N Karnezis, Jamie Magrill, Basile Tessier-Cloutier, Amy Lum, Janine Senz, C Blake Gilks, W Glenn McCluggage, David G Huntsman, Friedrich Kommoss
AIMS: Gynandroblastoma is a rare ovarian sex cord-stromal tumor characterized by the presence of both male (Sertoli and/or Leydig cells) and female (granulosa cells) components. We investigated the mutational status of DICER1, FOXL2 and AKT1 genes at hotspot regions that are known to be the key driving events in the development of Sertoli-Leydig cell tumor (SLCT), adult granulosa cell tumor (aGCT) and juvenile granulosa cell tumor (jGCT), respectively, to gain insights into the molecular pathogenesis of gynandroblastoma...
April 16, 2018: Histopathology
https://www.readbyqxmd.com/read/29587661/characteristics-and-outcome-of-the-coeur-canadian-validation-cohort-for-ovarian-cancer-biomarkers
#3
Cécile Le Page, Kurosh Rahimi, Martin Köbel, Patricia N Tonin, Liliane Meunier, Lise Portelance, Monique Bernard, Brad H Nelson, Marcus Q Bernardini, John M S Bartlett, Dimcho Bachvarov, Walter H Gotlieb, Blake Gilks, Jessica N McAlpine, Mark W Nachtigal, Alain Piché, Peter H Watson, Barbara Vanderhyden, David G Huntsman, Diane M Provencher, Anne-Marie Mes-Masson
BACKGROUND: Ovarian carcinoma is the most lethal gynecological malignancy due to early dissemination and acquired resistance to platinum-based chemotherapy. Reliable markers that are independent and complementary to clinical parameters are needed to improve the management of patients with this disease. The Canadian Ovarian Experimental Unified Resource (COEUR) provides researchers with biological material and associated clinical data to conduct biomarker validation studies. Using standards defined by the Canadian Tissue Repository Network (CTRNet), we have previously demonstrated the quality of the biological material from this resource...
March 27, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29517499/interpretation-of-p53-immunohistochemistry-in-endometrial-carcinomas-toward-increased-reproducibility
#4
Martin Köbel, Brigitte M Ronnett, Naveena Singh, Robert A Soslow, C Blake Gilks, W Glenn McCluggage
P53 immunohistochemistry has evolved into an accurate surrogate reflecting the underlying TP53 mutation status of a tumor, and has utility in the diagnostic workup of endometrial carcinomas. Recent work predominantly carried out in tubo-ovarian high-grade serous carcinoma has revealed 4 main patterns of p53 staining (normal/wild-type, complete absence, overexpression, and cytoplasmic); the latter 3 patterns are variably termed abnormal/aberrant/mutation-type and are strongly predictive of an underlying TP53 mutation...
March 6, 2018: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/29506471/a-population-based-analysis-of-germline-brca1-and-brca2-testing-among-ovarian-cancer-patients-in-an-era-of-histotype-specific-approaches-to-ovarian-cancer-prevention
#5
Gillian E Hanley, Jessica N McAlpine, Dianne Miller, David Huntsman, Kasmintan A Schrader, C Blake Gilks, Gillian Mitchell
BACKGROUND: Identifying female carriers of BRCA1 and BRCA2 mutations is imperative for prevention of ovarian cancer and breast cancer. There are five major histologic subtypes of ovarian cancer and high grade serous cancer (the most common) is reported in 75-100% of BRCA1 and BRCA2 mutation carriers. We examined histology-based referral to the Hereditary Cancer Program following an educational prevention campaign recommending BRCA1 and BRCA2 mutation screening for all high-grade serous cancer patients...
March 5, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29505428/molecular-classification-of-grade-3-endometrioid-endometrial-cancers-identifies-distinct-prognostic-subgroups
#6
Tjalling Bosse, Remi A Nout, Jessica N McAlpine, Melissa K McConechy, Heidi Britton, Yaser R Hussein, Carlene Gonzalez, Raji Ganesan, Jane C Steele, Beth T Harrison, Esther Oliva, August Vidal, Xavier Matias-Guiu, Nadeem R Abu-Rustum, Douglas A Levine, C Blake Gilks, Robert A Soslow
Our aim was to investigate whether molecular classification can be used to refine prognosis in grade 3 endometrial endometrioid carcinomas (EECs). Grade 3 EECs were classified into 4 subgroups: p53 abnormal, based on mutant-like immunostaining (p53abn); MMR deficient, based on loss of mismatch repair protein expression (MMRd); presence of POLE exonuclease domain hotspot mutation (POLE); no specific molecular profile (NSMP), in which none of these aberrations were present. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method (Log-rank test) and univariable and multivariable Cox proportional hazard models...
May 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29502561/myd88-and-tlr4-expression-in-epithelial-ovarian-cancer
#7
Matthew S Block, Robert A Vierkant, Peter F Rambau, Stacey J Winham, Philipp Wagner, Nadia Traficante, Aleksandra Tołoczko, Daniel G Tiezzi, Florin Andrei Taran, Peter Sinn, Weiva Sieh, Raghwa Sharma, Joseph H Rothstein, Teresa Ramón Y Cajal, Luis Paz-Ares, Oleg Oszurek, Sandra Orsulic, Roberta B Ness, Gregg Nelson, Francesmary Modugno, Janusz Menkiszak, Valerie McGuire, Bryan M McCauley, Marie Mack, Jan Lubiński, Teri A Longacre, Zheng Li, Jenny Lester, Catherine J Kennedy, Kimberly R Kalli, Audrey Y Jung, Sharon E Johnatty, Mercedes Jimenez-Linan, Allan Jensen, Maria P Intermaggio, Jillian Hung, Esther Herpel, Brenda Y Hernandez, Andreas D Hartkopf, Paul R Harnett, Prafull Ghatage, José M García-Bueno, Bo Gao, Sian Fereday, Ursula Eilber, Robert P Edwards, Christiani B de Sousa, Jurandyr M de Andrade, Anita Chudecka-Głaz, Georgia Chenevix-Trench, Alicia Cazorla, Sara Y Brucker, Jennifer Alsop, Alice S Whittemore, Helen Steed, Annette Staebler, Kirsten B Moysich, Usha Menon, Jennifer M Koziak, Stefan Kommoss, Susanne K Kjaer, Linda E Kelemen, Beth Y Karlan, David G Huntsman, Estrid Høgdall, Jacek Gronwald, Marc T Goodman, Blake Gilks, María José García, Peter A Fasching, Anna de Fazio, Suha Deen, Jenny Chang-Claude, Francisco J Candido Dos Reis, Ian G Campbell, James D Brenton, David D Bowtell, Javier Benítez, Paul D P Pharoah, Martin Köbel, Susan J Ramus, Ellen L Goode
OBJECTIVE: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. PATIENTS AND METHODS: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time...
March 2018: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/29449679/tert-promoter-mutation-in-adult-granulosa-cell-tumor-of-the-ovary
#8
Jessica A Pilsworth, Dawn R Cochrane, Zhouchunyang Xia, Geraldine Aubert, Anniina E M Färkkilä, Hugo M Horlings, Satoshi Yanagida, Winnie Yang, Jamie L P Lim, Yi Kan Wang, Ali Bashashati, Jacqueline Keul, Adele Wong, Kevin Norris, Sara Y Brucker, Florin-Andrei Taran, Bernhard Krämer, Annette Staebler, Esther Oliva, Sohrab P Shah, Stefan Kommoss, Friedrich Kommoss, C Blake Gilks, Duncan M Baird, David G Huntsman
The telomerase reverse transcriptase (TERT) gene is highly expressed in stem cells and silenced upon differentiation. Cancer cells can attain immortality by activating TERT to maintain telomere length and telomerase activity, which is a crucial step of tumorigenesis. Two somatic mutations in the TERT promoter (C228T; C250T) have been identified as gain-of-function mutations that promote transcriptional activation of TERT in multiple cancers, such as melanoma and glioblastoma. A recent study investigating TERT promoter mutations in ovarian carcinomas found C228T and C250T mutations in 15...
February 15, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29406447/bartholin-gland-carcinoma-clinicopathologic-features-including-p16-expression-and-clinical-outcome
#9
Tayyebeh Nazeran, Angela S Cheng, Anthony N Karnezis, Anna V Tinker, C Blake Gilks
Bartholin gland carcinomas are rare forms of vulvar malignancy and it is unclear what proportion is associated with high-risk human papilloma virus (HPV) infection. Our hospital archives were searched for all cases of Bartholin gland carcinoma from 1984 to 2017 (n=16). We excluded 3 adenoid cystic carcinomas, which were the subject of a previous study, leaving 13 cases. We reviewed all slides and performed immunostains for p16 as a surrogate biomarker for high-risk HPV. There were 12 squamous cell carcinomas (SCCs), including 1 SCC with transitional-like morphology and 1 papillary SCC, and 1 adenocarcinoma...
February 5, 2018: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/29369922/canadian-consensus-based-and-evidence-based-guidelines-for-benign-endometrial-pathology-reporting-in-biopsy-material
#10
Carlos Parra-Herran, Matthew Cesari, Bojana Djordjevic, Katherine Grondin, Mary Kinloch, Martin Köbel, Amrah Pirzada, Anna Plotkin, C Blake Gilks
Standardized terminology has proven benefits in cancer reporting; in contrast, reporting of benign diagnoses in endometrial biopsy currently lacks such standardization. Unification and update on the lexicon can provide the structure and consistency needed for optimal patient care and quality assurance purposes. The Special Interest Group in Gynecologic Pathology of the Canadian Association of Pathologists-Association Canadienne des Pathologistes (CAP-ACP) embarked in an initiative to address the current need for consensus terminology in benign endometrial biopsy pathology reporting...
April 19, 2018: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/29366348/case-report-an-identical-twin-with-sertoli-leydig-cell-tumor
#11
Kristy Cho, Jon C Havelock, Blake Gilks, Caitlin Dunne
Our report details the workup and management of a 43-year-old woman with an identical twin who presented with 2 years of virilization and secondary amenorrhea. Serum total testosterone was elevated. An MRI did not identify adnexal or adrenal pathology. Subsequent ovarian vein sampling demonstrated unilateral testosterone elevation. The patient underwent laparoscopic unilateral oophorectomy resulting in the diagnosis of Sertoli-Leydig cell tumor (SLCT). Although SLCT is a rare sex-cord ovarian tumor, it is associated with endometrial hyperplasia and malignancy...
January 24, 2018: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29249564/synchronous-tumours-of-the-female-reproductive-tract
#12
REVIEW
C Blake Gilks, Friedrich Kommoss
Many ovarian endometrioid carcinomas present with concurrent endometrial carcinoma, and these organ-confined, low-grade synchronous endometrial and ovarian tumours consistently behave as independent primary tumours, rather than a single advanced-stage carcinoma; they are associated with a very favourable prognosis and there is no need for adjuvant treatment. This phenomenon of synchronous tumours involving two or more sites within the female reproductive tract is well recognised, occurring in 1-2% of cases...
February 2018: Pathology
https://www.readbyqxmd.com/read/29234950/the-evolution-of-endometrial-carcinoma-classification-through-application-of-immunohistochemistry-and-molecular-diagnostics-past-present-and-future
#13
REVIEW
Emily A Goebel, August Vidal, Xavier Matias-Guiu, C Blake Gilks
Uterine cancer was first subclassified based on anatomic site, separating those tumours arising from the endometrium from cervical cancers. There was then further subclassification of endometrial cancers based on cell type, and this correlated with the Type I and Type II categories identified through the epidemiological studies of Bokhman, with endometrioid carcinoma corresponding (approximately) to Type I and serous carcinoma to Type II. These histotypes are not clearly separable in practice, however, with considerable interobserver variability in histotype diagnosis, especially for high-grade tumours...
December 12, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29148539/extrauterine-high-grade-serous-carcinomas-with-bilateral-adnexal-involvement-as-the-only-two-disease-sites-are-clonal-based-on-tp53-sequencing-results-implications-for-biology-classification-and-staging
#14
Naveena Singh, Asma Faruqi, Friedrich Kommoss, W Glenn McCluggage, Giorgia Trevisan, Janine Senz, Amy Lum, C Blake Gilks, Michael Anglesio
A previous multicenter study of 67 cases of Stage I/II tubo-ovarian high-grade serous carcinoma with complete tubal sampling identified 7 cases in which there were only two disease sites, comprising tumor involving opposite adnexa with no extra-adnexal involvement. This study aimed to determine whether such low-stage extrauterine high-grade serous carcinomas with only two sites of involvement, located on opposite adnexa, have identical or different TP53 mutations in order to investigate their clonal relationship...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29049607/dose-response-association-of-cd8-tumor-infiltrating-lymphocytes-and-survival-time-in-high-grade-serous-ovarian-cancer
#15
Ellen L Goode, Matthew S Block, Kimberly R Kalli, Robert A Vierkant, Wenqian Chen, Zachary C Fogarty, Aleksandra Gentry-Maharaj, Aleksandra Tołoczko, Alexander Hein, Aliecia L Bouligny, Allan Jensen, Ana Osorio, Andreas Hartkopf, Andy Ryan, Anita Chudecka-Głaz, Anthony M Magliocco, Arndt Hartmann, Audrey Y Jung, Bo Gao, Brenda Y Hernandez, Brooke L Fridley, Bryan M McCauley, Catherine J Kennedy, Chen Wang, Chloe Karpinskyj, Christiani B de Sousa, Daniel G Tiezzi, David L Wachter, Esther Herpel, Florin Andrei Taran, Francesmary Modugno, Gregg Nelson, Jan Lubiński, Janusz Menkiszak, Jennifer Alsop, Jenny Lester, Jesús García-Donas, Jill Nation, Jillian Hung, José Palacios, Joseph H Rothstein, Joseph L Kelley, Jurandyr M de Andrade, Luis Robles-Díaz, Maria P Intermaggio, Martin Widschwendter, Matthias W Beckmann, Matthias Ruebner, Mercedes Jimenez-Linan, Naveena Singh, Oleg Oszurek, Paul R Harnett, Peter F Rambau, Peter Sinn, Philipp Wagner, Prafull Ghatage, Raghwa Sharma, Robert P Edwards, Roberta B Ness, Sandra Orsulic, Sara Y Brucker, Sharon E Johnatty, Teri A Longacre, Eilber Ursula, Valerie McGuire, Weiva Sieh, Yanina Natanzon, Zheng Li, Alice S Whittemore, deFazio Anna, Annette Staebler, Beth Y Karlan, Blake Gilks, David D Bowtell, Estrid Høgdall, Francisco J Candido dos Reis, Helen Steed, Ian G Campbell, Jacek Gronwald, Javier Benítez, Jennifer M Koziak, Jenny Chang-Claude, Kirsten B Moysich, Linda E Kelemen, Linda S Cook, Marc T Goodman, María José García, Peter A Fasching, Stefan Kommoss, Suha Deen, Susanne K Kjaer, Usha Menon, James D Brenton, Paul DP Pharoah, Georgia Chenevix-Trench, David G Huntsman, Stacey J Winham, Martin Köbel, Susan J Ramus
Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. Objective: To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. Design, Setting, and Participants: This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium...
December 1, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28990983/pathology-of-ovarian-cancer-recent-insights-unveiling-opportunities-in-prevention
#16
Friedrich Kommoss, C Blake Gilks
Ovarian carcinomas were formerly referred to as "surface epithelial carcinomas," reflecting the belief that they all arise from the ovarian surface epithelium. It is now appreciated that most ovarian carcinomas originate from either fallopian tube or endometriotic epithelium, and how we approach prevention will thus differ between histotypes. The 5 histotypes of ovarian carcinoma (high-grade serous, clear cell, endometrioid, mucinous, and low-grade serous, in descending order of frequency) can be reproducibly diagnosed, and are distinct disease entities, differing with respect to genetic risk factors, molecular events during oncogenesis, patterns of spread, and response to chemotherapy...
December 2017: Clinical Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28930809/survival-benefit-of-adjuvant-radiotherapy-an-analysis-of-low-stage-invasive-ovarian-mucinous-carcinomas
#17
Aalok Kumar, Nhu Le, C Blake Gilks, Jennifer L Santos, Frances Wong, Kenneth Swenerton, Paul J Hoskins, Jessica N McAlpine, Anna V Tinker
OBJECTIVE: Our aim was to evaluate the population-based outcomes of stages I and II invasive ovarian mucinous carcinomas (MCs) treated with adjuvant platinum-based chemotherapy and abdominopelvic radiotherapy (XRT). METHODS: International Federation of Gynecology and Obstetrics stage I/II MC cases referred to the British Columbia Cancer Agency between 1984 and 2014 were reviewed. Chemotherapy (minimum of 3 cycles) and XRT were the institutional policy for stages IA/B (grade 2/3) and IC/II (any grade)...
November 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28914618/hereditary-breast-and-ovarian-cancer-syndrome-moving-beyond-brca1-and-brca2
#18
Lien N Hoang, Blake C Gilks
The recent implementation of next generation sequencing and multigene platforms has expanded the spectrum of hereditary breast and ovarian cancer syndrome, beyond the traditional genes BRCA1 and BRCA2. A large number of other moderate penetrance genes have now been uncovered, which also play critical roles in repairing double stranded DNA breaks through the homologous recombination pathway. This review discusses the landmark discoveries of BRCA1 and BRCA2, the homologous repair pathway and new genes discovered in hereditary breast and ovarian cancer syndrome, as well as their clinicopathologic significance and implications for genetic testing...
March 2018: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28678427/clear-cell-and-endometrioid-carcinomas-are-their-differences-attributable-to-distinct-cells-of-origin
#19
COMPARATIVE STUDY
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...
September 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
#20
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: The treatment of patients with tubo-ovarian high-grade serous carcinoma (HGSC) is increasingly based on diagnosis on small biopsy samples, and the first surgical sample is often taken post-chemotherapy. p53 and WT1 are important diagnostic markers for HGSC. The effect of neoadjuvant chemotherapy on p53 and WT1 expression has not been widely studied. We aimed to compare p53 and WT1 expression in paired pre-chemotherapy and post-chemotherapy samples of HGSC. METHODS AND RESULTS: Immunohistochemistry (IHC) was carried out for p53 and WT1 on paired omental HGSC samples pre-chemotherapy and post-chemotherapy...
June 1, 2017: Histopathology
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