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Record W3036702906 · doi:10.1038/s41416-020-0900-0

Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium

2020· article· en· W3036702906 on OpenAlexafffund
Filipe Correia Martins, Dominique‐Laurent Couturier, Anna Paterson, Anthony N. Karnezis, Christine Chow, Tayyebeh M. Nazeran, Adekunle Odunsi, Aleksandra Gentry‐Maharaj, Aleksandra Vrvilo, Alexander Hein, Aline Talhouk, Ana Osório, Andreas D. Hartkopf, Angela Brooks‐Wilson, Anna DeFazio, Anna Fischer, Arndt Hartmann, Brenda Y. Hernandez, Bryan M. McCauley, Chloe Karpinskyj, Christiani Bisinoto de Sousa, Claus Høgdall, Daniel Guimarães Tiezzi, Esther Herpel, Florin‐Andrei Taran, Francesmary Modugno, Gary L. Keeney, Gregg Nelson, Helen Steed, Honglin Song, Hugh Luk, Javier Benı́tez, Jennifer Alsop, Jennifer M. Koziak, Jenny Lester, Joseph H. Rothstein, Jurandyr Moreira de Andrade, Lene Lundvall, Luis Paz‐Ares, Luis A. Díaz‐Robles, Lynne R. Wilkens, María J. García, Maria P. Intermaggio, Marie‐Lyne Alcaraz, Mary Anne Brett, Matthias W. Beckmann, Mercedes Jimenez‐Liñan, Michael S. Anglesio, Michael E. Carney, Michael Schneider, Nadia Traficante, Nadja Pejovic, Naveena Singh, Nhu D. Le, Hans‐Peter Sinn, Prafull Ghatage, Ramona Erber, Robert P. Edwards, Robert A. Vierkant, Roberta B. Ness, Samuel Leung, Sandra Oršulić, Sara Y. Brucker, Scott H. Kaufmann, Sián Fereday, Simon A. Gayther, Stacey J. Winham, Stefan Kommoss, Tanja Pejović, Teri A. Longacre, Valerie McGuire, Valerie Rhenius, Weiva Sieh, Yurii B. Shvetsov, Alice S. Whittemore, Annette Staebler, Beth Y. Karlan, Cristina Rodríguez‐Antona, David D.L. Bowtell, Ellen L. Goode, Estrid Høgdall, Francisco José Cândido dos Reis, Jacek Gronwald, Jenny Chang‐Claude, Kirsten B. Moysich, Linda E. Kelemen, Linda S. Cook, Marc T. Goodman, Peter A. Fasching, Robin Crawford, Suha Deen, Usha Menon, David G. Huntsman, Martin Köbel, Susan J. Ramus, Paul D.P. Pharoah, James D. Brenton

Bibliographic record

VenueBritish Journal of Cancer · 2020
Typearticle
Languageen
FieldMedicine
TopicOvarian cancer diagnosis and treatment
Canadian institutionsBC Cancer AgencyAlberta Health ServicesRoyal Alexandra HospitalCanada's Michael Smith Genome Sciences CentreUniversity of British ColumbiaVancouver General HospitalUniversity of CalgaryVancouver Coastal Health
FundersMedical Research and Materiel CommandNational Cancer InstituteCancer Council TasmaniaNational Center for Advancing Translational SciencesMedical Research CouncilPeter MacCallum FoundationNational Center for Research ResourcesOak FoundationBC Cancer FoundationCanada Research ChairsConselho Nacional de Desenvolvimento Científico e TecnológicoNational Institutes of HealthCancer Institute NSWNational Health and Medical Research CouncilAmerican Cancer SocietyAcademy of Medical SciencesCalgary Laboratory ServicesUniversity of CambridgeUniversity College LondonCancer Research UKMichael Smith Health Research BCDeutsches KrebsforschungszentrumCancer Council VictoriaCancer AustraliaKræftens BekæmpelseBundesministerium für Bildung und ForschungNational Institute for Health and Care ResearchOvarian Cancer Australia
KeywordsOvarian cancerPTENPathologicalOncologyMedicinePathologyOvarian tissueOvaryCancerInternal medicineBiologyGeneticsPI3K/AKT/mTOR pathwayApoptosis

Abstract

fetched live from OpenAlex

BACKGROUND: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. METHODS: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests. RESULTS: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). CONCLUSIONS: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.037
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.050
GPT teacher head0.371
Teacher spread0.321 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations68
Published2020
Admission routes2
Has abstractyes

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