Journal ArticleDOI
Poor interobserver reproducibility in the diagnosis of high-grade endometrial carcinoma.
TLDR
There is a need for molecular tools to aid in the accurate and reproducible diagnosis of high-grade endometrioid carcinoma subtype.Abstract:
Patients with high-grade subtypes of endometrial carcinoma (grade 3 endometrioid, serous, clear cell, or carcinosarcoma) have a relatively poor prognosis. The specific subtype may be used to guide patient management, but there is little information on the reproducibility of subtype diagnosis in cases of high-grade endometrial carcinoma. Fifty-six cases diagnosed as a high-grade subtype of endometrial carcinoma were identified from the pathology archives of Vancouver General Hospital. All slides for each case were reviewed independently by 3 pathologists, who diagnosed the specific tumor subtype(s) and assigned the percentage of each subtype for mixed tumors. Agreement between observers was categorized as follows: major disagreement: (A) no consensus for low-grade endometrioid versus high-grade carcinoma (any subtype), or (B) no consensus with respect to the predominant high-grade subtype present; minor disagreement: consensus was reached about the cell type of the predominant component of a mixed tumor, but there was disagreement about the subtype of the minor component. A tissue microarray was constructed from these cases and immunostained for p16, ER, PR, PTEN, and p53. In 35 of 56 (62.5%) cases, there was agreement between all 3 reviewers regarding the subtype diagnosis of the exclusive (in pure tumors) or predominant (in mixed tumors) high-grade component. Of these cases, there was a minor disagreement (ie, disagreement about the minor high-grade component subtype in a mixed tumor) in 4 cases (4/56, 7.1%). In 20 of 56 (35.8%) cases there was a major disagreement; in 17 (30.4%) of these cases there was no consensus about the major subtype diagnosis, whereas in 3 (5.4%) cases there was disagreement about whether a component of high-grade endometrial carcinoma was present. In the final case, all 3 reviewers diagnosed the case as low-grade endometrioid carcinoma, disagreeing with the original diagnosis of high-grade carcinoma. The most frequent areas of disagreement were serous versus clear cell (7 cases) and serous versus grade 3 endometrioid (6 cases). Immunostaining results using the 5-marker immunopanel were then used to adjudicate in the 6 cases in which there was disagreement between reviewers with respect to serous versus endometrioid carcinoma, and these supported a diagnosis of serous carcinoma in 4 of 6 cases and endometrioid carcinoma in 2 of 6 cases. Pairwise comparison between the reviewers for the 20 cases classified as showing major disagreement was as follows: reviewer 1 and reviewer 2 agreed in 5/20 cases, reviewer 1 and reviewer 3 agreed in 7/20 cases, and reviewer 2 and reviewer 3 agreed in 8/20 cases, indicating that disagreements were not because of a single reviewer holding outlier opinions. Diagnostic consensus among 3 reviewers about the exclusive or major subtype of high-grade endometrial carcinoma was reached in only 35/56 (62.5%) cases, and in 4 of these cases there was disagreement about the minor component present. This poor reproducibility did not reflect systematic bias on the part of any 1 reviewer. There is a need for molecular tools to aid in the accurate and reproducible diagnosis of high-grade endometrial carcinoma subtype.read more
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Journal ArticleDOI
Integrated genomic characterization of endometrial carcinoma
Gad Getz,Stacey Gabriel,Kristian Cibulskis,Eric S. Lander,Andrey Sivachenko,Carrie Sougnez,Michael S. Lawrence,Cyriac Kandoth,David J. Dooling,Robert S. Fulton,Lucinda Fulton,Joelle Kalicki-Veizer,Michael D. McLellan,Michelle O'Laughlin,Heather Schmidt,Richard K. Wilson,Kai Ye,Ding Li,Adrian Ally,Miruna Balasundaram,Inanc Birol,Yaron S.N. Butterfield,Rebecca Carlsen,Candace Carter,Andy Chu,Eric Chuah,Hye Jung E. Chun,Noreen Dhalla,Ranabir Guin,Carrie Hirst,Robert A. Holt,Steven J.M. Jones,Darlene Lee,Haiyan I. Li,Marco A. Marra,Michael Mayo,Richard A. Moore,Andrew J. Mungall,Patrick Plettner,Jacqueline E. Schein,Payal Sipahimalani,Angela Tam,Richard Varhol,A. Gordon Robertson,Andrew D. Cherniack,Itai Pashtan,Gordon Saksena,Robert C. Onofrio,Steven E. Schumacher,Barbara Tabak,Scott L. Carter,Bryan Hernandez,Jeff Gentry,Helga B. Salvesen,Helga B. Salvesen,Kristin G. Ardlie,Wendy Winckler,Rameen Beroukhim,Rameen Beroukhim,Matthew Meyerson,Angela Hadjipanayis,Semin Lee,Harshad S. Mahadeshwar,Peter J. Park,Alexei Protopopov,Xiaojia Ren,Sahil Seth,Xingzhi Song,Jiabin Tang,Ruibin Xi,Lixing Yang,Zeng Dong,Raju Kucherlapati,Lynda Chin,Lynda Chin,Jianhua Zhang,Jianhua Zhang,J. Todd Auman,Saianand Balu,Tom Bodenheimer,Elizabeth Buda,D. Neil Hayes,Alan P. Hoyle,Stuart R. Jefferys,Corbin D. Jones,Shaowu Meng,Piotr A. Mieczkowski,Lisle E. Mose,Joel S. Parker,Charles M. Perou,Jeff Roach,Shi Yan,Janae V. Simons,Mathew G. Soloway,Donghui Tan,Michael D. Topal,Scot Waring,Junyuan Wu,Katherine A. Hoadley,Stephen B. Baylin,Moiz S. Bootwalla,Phillip H. Lai,Timothy J. Triche,David Van Den Berg,Daniel J. Weisenberger,Peter W. Laird,Hui Shen,Hui Shen,Hui Shen,Juok Cho,Daniel DiCara,Scott Frazer,David I. Heiman,Rui Jing,Pei Lin,Will Mallard,Petar Stojanov,Doug Voet,Hailei Zhang,Lihua Zou,Michael S. Noble,Sheila Reynolds,Ilya Shmulevich,B. Arman Aksoy,Yevgeniy Antipin,Giovanni Ciriello,Gideon Dresdner,Jianjiong Gao,Benjamin Gross,Anders Jacobsen,Marc Ladanyi,Boris Reva,Chris Sander,Rileen Sinha,S. Onur Sumer,Barry S. Taylor,Ethan Cerami,Nils Weinhold,Nikolaus Schultz,Ronglai Shen,Stephen C. Benz,Theodore C. Goldstein,David Haussler,Sam Ng,Christopher Szeto,Joshua M. Stuart,Christopher C. Benz,Christina Yau,Wei Zhang,Matti Annala,Matti Annala,Bradley M. Broom,Tod D. Casasent,Zhenlin Ju,Han Liang,Guoyan Liu,Yiling Lu,Anna K. Unruh,Chris Wakefield,John N. Weinstein,Nianxiang Zhang,Yuexin Liu,Russell Broaddus,Rehan Akbani,Gordon B. Mills,Christopher Adams,Thomas Barr,Aaron D. Black,Jay Bowen,John Deardurff,Jessica Frick,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Thomas Grossman,Hollie A. Harper,Melissa Hart-Kothari,Carmen Helsel,Aaron Hobensack,Harkness Kuck,Kelley Kneile,Kristen M. Leraas,Tara M. Lichtenberg,Cynthia McAllister,Robert E. Pyatt,Nilsa C. Ramirez,Nilsa C. Ramirez,Teresa R. Tabler,Nathan Vanhoose,Peter White,Lisa Wise,Erik Zmuda,Nandita Barnabas,Charlenia Berry-Green,Victoria Blanc,Lori Boice,Michael Button,Adam M. Farkas,Alexander A. Green,Jean MacKenzie,Dana Nicholson,Steve E. Kalloger,C. Blake Gilks,Beth Y. Karlan,Jenny Lester,Sandra Orsulic,Mark E. Borowsky,Mark G. Cadungog,Christine Czerwinski,Lori Huelsenbeck-Dill,Mary Iacocca,Nicholas J. Petrelli,Brenda Rabeno,Gary Witkin,Elena Nemirovich-Danchenko,Olga Potapova,D L Rotin,Andrew Berchuck,Michael J. Birrer,P.J. DiSaia,Laura Monovich,Erin Curley,Johanna Gardner,David Mallery,Robert Penny,Sean C. Dowdy,Boris Winterhoff,Linda Dao,Bobbie S. Gostout,Alexandra Meuter,Attila Teoman,Fanny Dao,Narciso Olvera,Faina Bogomolniy,Karuna Garg,Robert A. Soslow,Mikhail Abramov,John M. S. Bartlett,Sugy Kodeeswaran,Jeremy Parfitt,Fedor Moiseenko,Blaise A. Clarke,Marc T. Goodman,Michael E. Carney,Rayna K. Matsuno,Jennifer O. Fisher,Mei Huang,W. Kimryn Rathmell,Leigh B. Thorne,Linda Van Le,Rajiv Dhir,Robert Edwards,Esther Elishaev,Kristin K. Zorn,Paul J. Goodfellow,Paul J. Goodfellow,Paul J. Goodfellow,David G. Mutch,Ari B. Kahn,Daphne W. Bell,Pamela M. Pollock,Chen Wang,David A. Wheeler,Eve Shinbrot,Li Ding,Elaine R. Mardis,Brenda Ayala,Anna L. Chu,Mark A. Jensen,Prachi Kothiyal,Todd Pihl,Joan Pontius,David Pot,Eric E. Snyder,Deepak Srinivasan,Kenna R. Mills Shaw,Margi Sheth,Tanja Davidsen,Greg Eley,Martin L. Ferguson,Liming Yang,Mark S. Guyer,Bradley A. Ozenberger,Heidi J. Sofia,Douglas A. Levine +283 more
TL;DR: In this paper, the authors performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and-sequencing-based technologies, and classified them into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy number high.
Integrated genomic characterization of endometrial carcinoma
Gad Getz,Stacey Gabriel,Kristian Cibulskis,Eric S. Lander,Andrey Sivachenko,Carrie Sougnez,Michael S. Lawrence,Cyriac Kandoth,David J. Dooling,Robert S. Fulton,Lucinda Fulton,Joelle Kalicki-Veizer,Michael D. McLellan,Michelle O'Laughlin,Heather Schmidt,Richard K. Wilson,Kai Ye,Li Ding,Elaine R. Mardis,Adrian Ally,Miruna Balasundaram,Inanc Birol,Yaron S. Butterfield,Rebecca Carlsen,Candace D. Carter,Andy Chu,Eric Chuah,Hye Jung E. Chun,Noreen Dhalla,Ranabir Guin,Carrie Hirst,Robert A. Holt,Steven J.M. Jones,Darlene Lee,Haiyan I. Li,Marco A. Marra,Michael Mayo,Richard A. Moore,Andrew J. Mungall,Patrick Plettner,Jacqueline E. Schein,Payal Sipahimalani,Angela Tam,Richard Varhol,A. Gordon Robertson,Andrew D. Cherniack,Itai Pashtan,Gordon Saksena,Robert C. Onofrio,Steven E. Schumacher,Barbara Tabak,Scott L. Carter,Bryan Hernandez,Jeff Gentry,Helga B. Salvesen,Kristin Ardlie,Wendy Winckler,Rameen Beroukhim,Matthew Meyerson,Angela Hadjipanayis,Semin Lee,Harshad S. Mahadeshwar,Peter J. Park,Alexei Protopopov,Xiaojia Ren,Sahil Seth,Xingzhi Song,Jiabin Tang,Ruibin Xi,Lixing Yang,Dong Zeng,Raju Kucherlapati,Lynda Chin,Jianhua Zhang,J. Todd Auman,Saianand Balu,Tom Bodenheimer,Elizabeth Buda,D. Neil Hayes,Alan P. Hoyle,Stuart R. Jefferys,Corbin D. Jones,Shaowu Meng,Piotr A. Mieczkowski,Lisle E. Mose,Joel S. Parker,Charles M. Perou,Jeff Roach,Yan Shi,Janae V. Simons,Mathew G. Soloway,Donghui Tan,Michael D. Topal,Scot Waring,Junyuan Wu,Katherine A. Hoadley,Stephen B. Baylin,Moiz S. Bootwalla,Phillip H. Lai,Timothy J. Triche,David Van Den Berg,Daniel J. Weisenberger,Peter W. Laird,Hui Shen,Juok Cho,Daniel DiCara,Scott Frazer,David I. Heiman,Rui Jing,Pei Lin,Will Mallard,Petar Stojanov,Doug Voet,Hailei Zhang,Lihua Zou,Michael S. Noble,Sheila M. Reynolds,Ilya Shmulevich,B. Arman Aksoy,Yevgeniy Antipin,Giovanni Ciriello,Gideon Dresdner,Jianjiong Gao,Benjamin Gross,Anders Jacobsen,Marc Ladanyi,Boris Reva,Chris Sander,Rileen Sinha,S. Onur Sumer,Barry S. Taylor,Ethan Cerami,Nils Weinhold,Nikolaus Schultz,Ronglai Shen,Stephen C. Benz,Theodore C. Goldstein,David Haussler,Sam Ng,Christopher Szeto,Joshua M. Stuart,Christopher C. Benz,Christina Yau,Wei Zhang,Matti Annala,Bradley M. Broom,Tod D. Casasent,Zhenlin Ju,Han Liang,Guoyan Liu,Yiling Lu,Anna K. Unruh,Chris Wakefield,John N. Weinstein,Nianxiang Zhang,Yuexin Liu,Russell Broaddus,Rehan Akbani,Gordon B. Mills,Christopher Adams,Thomas Barr,Aaron D. Black,Jay Bowen,John Deardurff,Jessica Frick,Julie M. Gastier-Foster,Thomas Grossman,Hollie A. Harper,Melissa Hart-Kothari,Carmen Helsel,Aaron Hobensack,Harkness Kuck,Kelley Kneile,Kristen M. Leraas,Tara M. Lichtenberg,Cynthia McAllister,Robert E. Pyatt,Nilsa C. Ramirez,Teresa R. Tabler,Nathan Vanhoose,Peter White,Lisa Wise,Erik Zmuda,Nandita Barnabas,Charlenia Berry-Green,Victoria Blanc,Lori Boice,Michael Button,Adam M. Farkas,Alexander A. Green,Jean MacKenzie,Dana Nicholson,Steve E. Kalloger,C Blake Gilks,Beth Y. Karlan,Jenny Lester,Sandra Orsulic,Mark L. Borowsky,Mark G. Cadungog,Christine Czerwinski,Lori Huelsenbeck-Dill,Mary Iacocca,Nicholas J. Petrelli,Brenda Rabeno,Gary Witkin,Elena Nemirovich-Danchenko,Olga Potapova,D L Rotin,Andrew Berchuck,Michael J. Birrer,P.J. DiSaia,Laura Monovich,Erin Curley,Johanna Gardner,David Mallery,Robert Penny,Sean C. Dowdy,Boris Winterhoff,Linda Dao,Bobbie S. Gostout,Alexandra Meuter,Attila Teoman,Fanny Dao,Narciso Olvera,Faina Bogomolniy,Karuna Garg,Robert A. Soslow,Douglas A. Levine,Mikhail Abramov,John M. S. Bartlett,Sugy Kodeeswaran,Jeremy Parfitt,Fedor Moiseenko,Blaise A. Clarke,Marc T. Goodman,Michael E. Carney,Rayna K. Matsuno,Jennifer C. Fisher,Mei Huang,W. Kimryn Rathmell,Leigh B. Thorne,Linda Van Le,Rajiv Dhir,Robert R. Edwards,Esther Elishaev,Kristin K. Zorn,Paul J. Goodfellow,David G. Mutch,Ari B. Kahn,Daphne W. Bell,Pamela M. Pollock,Chen Wang,David A. Wheeler,Eve Shinbrot,Brenda Ayala,Anna L. Chu,Mark A. Jensen,Prachi Kothiyal,Todd Pihl,Joan Pontius,David A. Pot,Eric E. Snyder,Deepak Srinivasan,Kenna R. Mills Shaw,Margi Sheth,Tanja Davidsen,Greg Eley Martin L. Ferguson,John A. Demchok,Liming Yang,Mark S. Guyer,Bradley A. Ozenberger,Heidi J. Sofia +271 more
TL;DR: The genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours, and these features are classified into four categories: POLE ultramutated, microsatellite instability hypermutated, copy- number low, and copy-number high.
Journal ArticleDOI
A clinically applicable molecular-based classification for endometrial cancers
Aline Talhouk,Melissa K. McConechy,Samuel C.Y. Leung,H. H. Li-Chang,Janice S. Kwon,Nataliya Melnyk,Winnie Yang,Janine Senz,Niki Boyd,Anthony N. Karnezis,David G. Huntsman,C. B. Gilks,Jessica N. McAlpine +12 more
TL;DR: Molecular classification of ECs can be achieved using clinically applicable methods on formalin-fixed paraffin-embedded samples, and provides independent prognostic information beyond established risk factors, and has potential in guiding treatment for individuals with endometrial carcinoma and in stratifying cases in future clinical trials.
Journal ArticleDOI
Confirmation of ProMisE: A simple, genomics‐based clinical classifier for endometrial cancer
Aline Talhouk,Melissa K. McConechy,Samuel Leung,Winnie Yang,Amy Lum,Janine Senz,Niki Boyd,Judith Pike,Michael S. Anglesio,Janice S. Kwon,Anthony N. Karnezis,David G. Huntsman,C. Blake Gilks,Jessica N. McAlpine +13 more
TL;DR: 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.
Journal ArticleDOI
Classification of endometrial carcinoma: more than two types.
TL;DR: An overview of traditional and newer genomic classifications of endometrial cancer is provided and how a classification system that incorporates genomic and histopathological features to define biologically and clinically relevant subsets of the disease would be useful is discussed.
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Integrated genomic characterization of endometrial carcinoma
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