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JOURNAL ARTICLE
Amy Jamieson, Juliana Sobral de Barros, Dawn R Cochrane, J Maxwell Douglas, Sameer Shankar, Branden J Lynch, Samuel Leung, Spencer Martin, Janine Senz, Amy Lum, Yvette Drew, C Blake Gilks, David G Huntsman, Jessica N McAlpine
PURPOSE: Shallow whole genome sequencing (sWGS) can detect copy number (CN) aberrations. In high-grade serous ovarian (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers (ECs) to identify additional prognostic stratification and therapeutic opportunities. EXPERIMENTAL DESIGN: sWGS and targeted panel sequencing was performed on formalin-fixed paraffin-embedded p53abn ECs...
March 27, 2024: Clinical Cancer Research
#2
JOURNAL ARTICLE
Amy Jamieson, Marcel Grube, Samuel Leung, Derek Chiu, Amy Lum, Janice S Kwon, Aline Talhouk, Blake Gilks, Stefan Kommoss, Jessica N McAlpine
OBJECTIVES: Optimal management of patients with stage IA p53abn endometrial cancer without myoinvasion, classified as intermediate risk in the 2020 European Society of Gynaecological Oncology, European Society for Radiotherapy and Oncology, and European Society of Pathology (ESGO-ESTRO-ESP) guidelines, and the 2022 European Society of Medical Oncology (ESMO) guidelines, is currently unclear. Practice varies from surgery alone to adjuvant radiation±chemotherapy. Our aim was to assess the risk of disease recurrence in patients with stage IA p53abn endometrial cancer without myoinvasion compared with stage IA with myoinvasion (<50%)...
February 22, 2024: International Journal of Gynecological Cancer
#3
JOURNAL ARTICLE
Anne Kathrin Höhn, Mirjam Forberger, Mona Alfaraidi, C Blake Gilks, Christine Elisabeth Brambs, Michael Höckel, Lynn Hoang, Naveena Singh, Lars-Christian Horn
OBJECTIVE: Vulvar squamous cell carcinoma (VSCC) can be stratified into three molecular subtypes based on the immunoexpression of p16 and p53: HPV-independent p53-abnormal (p53abn) (most common, biologically aggressive), HPV-associated, with p16-overexpression (second most common, prognostically more favourable) and more recently recognised HPV-independent p53-wildtype (p53wt) (rarest subtype, prognostically intermediate). Our aim was to determine whether molecular subtypes can be reliably identified in pre-operative biopsies and whether these correspond to the subsequent vulvectomy specimen...
February 10, 2024: Gynecologic Oncology
#4
JOURNAL ARTICLE
Jutta Huvila, Amy Jamieson, Jennifer Pors, Lynn Hoang, Jelena Mirkovic, Dawn Cochrane, Jessica N McAlpine, C Blake Gilks
INTRODUCTION: Our aim was to assess the molecular subtype(s) and perform a detailed morphologic review of tumors diagnosed as carcinosarcoma in a population-based cohort. METHODS: Forty-one carcinosarcomas were identified from a cohort of 973 endometrial carcinomas diagnosed in 2016. We assessed immunostaining and sequencing data and undertook expert pathology reviews of these cases as well as all subsequently diagnosed (post-2016) carcinosarcomas of no specific molecular profile (NSMP) molecular subtype (n=3) from our institutions...
February 2, 2024: International Journal of Gynecological Pathology
#5
JOURNAL ARTICLE
Sanne Vermorgen, Thijs Gelton, Peter Bult, Heidi V N Kusters-Vandevelde, Jitka Hausnerová, Koen Van de Vijver, Ben Davidson, Ingunn Marie Stefansson, Loes F S Kooreman, Adelina Qerimi, Jutta Huvila, Blake Gilks, Maryam Shahi, Saskia Zomer, Carla Bartosch, Johanna Ma Pijnenborg, Johan Bulten, Francesco Ciompi, Michiel Simons
Endometrial biopsies are important in the diagnostic work-up of women who present with abnormal uterine bleeding or women with hereditary risk of endometrial cancer. In general, about 10% of all endometrial biopsies demonstrate endometrial (pre)malignancy that requires specific treatment. As the diagnostic evaluation of mostly benign cases results in a substantial workload for pathologists, artificial intelligence (AI) assisted pre-selection of biopsies could optimize the workflow. This study aimed to assess the feasibility of AI-assisted diagnosis for endometrial biopsies (ENDO-AID), trained on daily-practice whole slide images instead of highly selected images...
December 26, 2023: Modern Pathology
#6
JOURNAL ARTICLE
Felix K F Kommoss, Amy Jamieson, Jessica N McAlpine, C Blake Gilks
No abstract text is available yet for this article.
December 21, 2023: American Journal of Surgical Pathology
#7
JOURNAL ARTICLE
Raji Ganesan, C Blake Gilks
No abstract text is available yet for this article.
January 2024: Histopathology
#8
JOURNAL ARTICLE
Spencer D Martin, Karina C Martin, C Blake Gilks, Richard I Crawford, Lien N Hoang
Vulvovaginal melanoma (VVM) is a rare but deadly disease, accounting for 5% of all vulvar malignancies, with a 5-yr survival rate of only 47% for all stages of the disease. VVM is a distinct subset of melanoma, with a unique genomic profile and underlying pathogenesis unassociated with sun exposure. Distinguishing these rare malignancies from very common pigmented lesions of the vulva and vagina is challenging as histologic features often overlap between entities. PReferentially expressed Antigen in MElanoma (PRAME) is a melanoma-associated protein, and immunohistochemistry (IHC) for PRAME distinguishes cutaneous, oral mucosal, and retinal melanoma from atypical nevi...
December 6, 2023: International Journal of Gynecological Pathology
#9
Flurina A M Saner, Kazuaki Takahashi, Timothy Budden, Ahwan Pandey, Dinuka Ariyaratne, Tibor A Zwimpfer, Nicola S Meagher, Sian Fereday, Laura Twomey, Kathleen I Pishas, Therese Hoang, Adelyn Bolithon, Nadia Traficante, Kathryn Alsop, Elizabeth L Christie, Eun-Young Kang, Gregg S Nelson, Prafull Ghatage, Cheng-Han Lee, Marjorie J Riggan, Jennifer Alsop, Matthias W Beckmann, Jessica Boros, Alison H Brand, Angela Brooks-Wilson, Michael E Carney, Penny Coulson, Madeleine Courtney-Brooks, Kara L Cushing-Haugen, Cezary Cybulski, Mona A El-Bahrawy, Esther Elishaev, Ramona Erber, Simon A Gayther, Aleksandra Gentry-Maharaj, C Blake Gilks, Paul R Harnett, Holly R Harris, Arndt Hartmann, Alexander Hein, Joy Hendley, Aocs Group, Brenda Y Hernandez, Anna Jakubowska, Mercedes Jimenez-Linan, Michael E Jones, Scott H Kaufmann, Catherine J Kennedy, Tomasz Kluz, Jennifer M Koziak, Björg Kristjansdottir, Nhu D Le, Marcin Lener, Jenny Lester, Jan Lubiński, Constantina Mateoiu, Sandra Orsulic, Matthias Ruebner, Minouk J Schoemaker, Mitul Shah, Raghwa Sharma, Mark E Sherman, Yurii B Shvetsov, Naveena Singh, T Rinda Soong, Helen Steed, Paniti Sukumvanich, Aline Talhouk, Sarah E Taylor, Robert A Vierkant, Chen Wang, Martin Widschwendter, Lynne R Wilkens, Stacey J Winham, Michael S Anglesio, Andrew Berchuck, James D Brenton, Ian Campbell, Linda S Cook, Jennifer A Doherty, Peter A Fasching, Renée T Fortner, Marc T Goodman, Jacek Gronwald, David G Huntsman, Beth Y Karlan, Linda E Kelemen, Usha Menon, Francesmary Modugno, Paul D P Pharoah, Joellen M Schildkraut, Karin Sundfeldt, Anthony J Swerdlow, Ellen L Goode, Anna DeFazio, Martin Köbel, Susan J Ramus, David D L Bowtell, Dale W Garsed
BACKGROUND: Somatic loss of the tumour suppressor RB1 is a common event in tubo-ovarian high-grade serous carcinoma (HGSC), which frequently co-occurs with alterations in homologous recombination DNA repair genes including BRCA1 and BRCA2 ( BRCA ). We examined whether tumour expression of RB1 was associated with survival across ovarian cancer histotypes (HGSC, endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous carcinoma (LGSC)), and how co-occurrence of germline BRCA pathogenic variants and RB1 loss influences long-term survival in a large series of HGSC...
November 10, 2023: medRxiv
#10
REVIEW
W Glenn McCluggage, Tjalling Bosse, C Blake Gilks, Brooke E Howitt, Jessica N McAlpine, Marisa R Nucci, Joseph T Rabban, Naveena Singh, Karen L Talia, Carlos Parra-Herran
An updated International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial carcinoma was introduced in June 2023. The new system represents a significant departure from traditional endometrial and other gynecological carcinoma staging systems which are agnostic of parameters such as tumor type, tumor grade, lymphovascular space invasion, and molecular alterations. The updated system, which incorporates all of these 'non-anatomical' parameters, is an attempt to make staging more personalized and relevant to patient prognostication and management, and to align with the European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) risk stratification...
November 7, 2023: International Journal of Gynecological Cancer
#11
Stephanie A Scott, Marta Llaurado Fernandez, Hannah Kim, Laurie Elit, Melica Nourmoussavi, Sarah Glaze, Lesley Roberts, Saul L Offman, Kurosh Rahimi, Alice Lytwyn, Monalisa Sur, C Blake Gilks, Kara Matheson, Martin Köbel, Amy Dawson, Anna V Tinker, Janice S Kwon, Paul Hoskins, Jennifer L Santos, Andrea Cheung, Diane Provencher, Mark S Carey
No abstract text is available yet for this article.
November 2022: Gynecologic Oncology
#12
JOURNAL ARTICLE
Felix Kf Kommoss, Cheng-Han Lee, Basile Tessier-Cloutier, C Blake Gilks, Colin Jr Stewart, Andreas von Deimling, Martin Köbel
Mesonephric-like adenocarcinoma (MLA) of the female genital tract is an uncommon histotype that can arise in both the endometrium and the ovary. The exact cell of origin and histogenesis currently remain unknown. Here, we investigated whole genome DNA methylation patterns and copy number variations (CNVs) in a series of MLAs in the context of a large cohort of various gynaecological carcinoma types. CNV analysis of 19 MLAs uncovered gains of chromosomes 1q (18/19, 95%), 10 (15/19, 79%), 12 (14/19, 74%), and 2 (10/19, 53%), as well as loss of chromosome 1p (7/19, 37%)...
October 18, 2023: Journal of Pathology
#13
JOURNAL ARTICLE
Amy Jamieson, Lisa Vermij, Claire J H Kramer, Jan J Jobsen, Ina Jürgemlienk-Schulz, Ludy Lutgens, Jan Willem Mens, Marie A D Haverkort, Annerie Slot, Remi A Nout, Jan Oosting, Joseph Carlson, Brooke E Howitt, Philip P C Ip, Sigurd F Lax, W Glenn McCluggage, Naveena Singh, Jessica N McAlpine, Carien L Creutzberg, Nanda Horeweg, C Blake Gilks, Tjalling Bosse
PURPOSE: The clinical significance of the p53-abnormal (p53abn) molecular subtype in stage I low-grade endometrioid endometrial carcinoma (EEC) is debated. We aimed to review pathologic and molecular characteristics, and outcomes of stage I low-grade p53abn EEC in a large international cohort. EXPERIMENTAL DESIGN: Previously diagnosed stage I p53abn EC (POLE-wild-type, mismatch repair-proficient) low-grade EEC from Canadian retrospective cohorts and PORTEC-1&2 trials were included...
December 1, 2023: Clinical Cancer Research
#14
JOURNAL ARTICLE
Jutta Huvila, Emily F Thompson, Jamie Vanden Broek, Amy Lum, Janine Senz, Samuel Leung, C Blake Gilks, Martin Köbel, Jessica N McAlpine, Amy Jamieson
AIMS: The significance of subclonal expression of p53 (abrupt transition from wild-type to mutant-pattern staining) is not well understood, and the arbitrary diagnostic cut-off of 10% between NSMP and p53abn molecular subtypes of endometrial carcinoma (EC) has not been critically assessed. Our aim was to characterise subclonal p53 and discrepant p53 expression/TP53 sequencing results in EC and assess their clinical significance. METHODS AND RESULTS: Subclonal p53 immuostaining on whole sections from 957 ECs was recorded...
December 2023: Histopathology
#15
JOURNAL ARTICLE
Yemin Wang, Shary Yuting Chen, Monica Ta, Janine Senz, Lan Valerie Tao, Shelby Thornton, Nirupama Tamvada, Winnie Yang, Yana Moscovitz, Eunice Li, Jingjie Guo, Cindy Shen, J Maxwell Douglas, Amal M El-Naggar, Felix K F Kommoss, T Michael Underhill, Naveena Singh, C Blake Gilks, Gregg B Morin, David G Huntsman
DICER1 is an RNase III enzyme essential for microRNA (miRNA) biogenesis through cleaving pre-miRNA hairpins. Germline loss-of-function DICER1 mutations underlie the development of DICER1 syndrome, a rare genetic disorder that predisposes children to cancer development in organs such as lung, gynecologic tract, kidney, and brain. Unlike classical tumor suppressors, the somatic "second hit" in DICER1 syndrome-associated cancers does not fully inactivate DICER1 but impairs its RNase IIIb activity only, suggesting a noncanonical two-hit hypothesis...
July 26, 2023: Cancer Research
#16
JOURNAL ARTICLE
Amy Jamieson, Melissa K McConechy, Amy Lum, Samuel Leung, Emily F Thompson, Janine Senz, Aline Talhouk, David G Huntsman, Ali Bashashati, C Blake Gilks, Jessica N McAlpine
OBJECTIVES: Despite recommendations for integrating molecular classification of endometrial cancers (EC) into pathology reporting and clinical management, uptake is inconsistent. To assign ProMisE subtype, all molecular components must be available (POLE mutation status, mismatch repair (MMR) and p53 immunohistochemistry (IHC)) and often these are assessed at different stages of care and/or at different centres resulting in delays in treatment. We assessed a single-test DNA-based targeted next generation sequencing (NGS) molecular classifier (ProMisE NGS), comparing concordance and prognostic value to the original ProMisE classifier...
June 13, 2023: Gynecologic Oncology
#17
JOURNAL ARTICLE
Anne Sophie V M Van den Heerik, Natalja T Ter Haar, Lisa Vermij, Jan J Jobsen, Mariel Brinkhuis, Suzan M Roothaan, Alicia Leon-Castillo, Gitte Ortoft, Estrid Hogdall, Claus Hogdall, Tom Van Wezel, Ludy C H W Lutgens, Marie A D Haverkort, Jas Khattra, Jessica N McAlpine, Carien L Creutzberg, Vincent T H B M Smit, C Blake Gilks, Nanda Horeweg, Tjalling Bosse
PURPOSE: Detection of 11 pathogenic variants in the POLE gene in endometrial cancer (EC) is critically important to identify women with a good prognosis and reduce overtreatment. Currently, POLE status is determined by DNA sequencing, which can be expensive, relatively time-consuming, and unavailable in hospitals without specialized equipment and personnel. This may hamper the implementation of POLE -testing in clinical practice. To overcome this, we developed and validated a rapid, low-cost POLE hotspot test by a quantitative polymerase chain reaction (qPCR) assay, QPOLE ...
May 2023: JCO global oncology
#18
EDITORIAL
Jennifer Pors, Lynn Hoang, Naveena Singh, C Blake Gilks
No abstract text is available yet for this article.
June 2023: Histopathology
#19
Amy Jamieson, Jutta Huvila, Derek Chiu, Emily F Thompson, Stephanie Scott, Shannon Salvador, Danielle Vicus, Limor Helpman, Walter Gotlieb, Sarah Kean, Vanessa Samouelian, Martin Köbel, Mary Kinloch, Carlos Parra-Herran, Saul Offman, Katherine Grondin, Julie Irving, Amy Lum, Janine Senz, Samuel Leung, Melissa K McConechy, Marie Plante, Stefan Kommoss, David G Huntsman, Aline Talhouk, C Blake Gilks, Jessica N McAlpine
No abstract text is available yet for this article.
May 12, 2023: Modern Pathology
#20
JOURNAL ARTICLE
Felix K F Kommoss, Anne-Sophie Chong, Anne-Laure Chong, Elke Pfaff, David T W Jones, Laura S Hiemcke-Jiwa, Lennart A Kester, Uta Flucke, Manfred Gessler, Daniel Schrimpf, Felix Sahm, Blaise A Clarke, Colin J R Stewart, Yemin Wang, C Blake Gilks, Friedrich Kommoss, David G Huntsman, Ulrich Schüller, Christian Koelsche, W Glenn McCluggage, Andreas von Deimling, William D Foulkes
DICER1 syndrome is a tumor predisposition syndrome that is associated with up to 30 different neoplastic lesions, usually affecting children and adolescents. Here we identify a group of mesenchymal tumors which is highly associated with DICER1 syndrome, and molecularly distinct from other DICER1-associated tumors. This group of DICER1-associated mesenchymal tumors encompasses multiple well-established clinicopathological tumor entities and can be further divided into three clinically meaningful classes designated "low-grade mesenchymal tumor with DICER1 alteration" (LGMT DICER1), "sarcoma with DICER1 alteration" (SARC DICER1), and primary intracranial sarcoma with DICER1 alteration (PIS DICER1)...
March 25, 2023: Nature Communications
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