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Record W4353029051 · doi:10.1002/cjp2.311

p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study

2023· article· en· W4353029051 on OpenAlexafffund
Martin Köbel, Eunyoung Kang, Ashley Weir, Peter Rambau, Cheng‐Han Lee, Gregg Nelson, Prafull Ghatage, Nicola S. Meagher, Marjorie J. Riggan, Jennifer Alsop, Michael S. Anglesio, Matthias W. Beckmann, Christiani Bisinotto, M.M. Boisen, Jessica Boros, Alison H. Brand, Angela Brooks‐Wilson, Michael E. Carney, Penny Coulson, Madeleine Courtney‐Brooks, Kara L. Cushing‐Haugen, Cezary Cybulski, Suha Deen, Mona El‐Bahrawy, Esther Elishaev, Ramona Erber, Sián Fereday, Anna Fischer, Simon A. Gayther, Arántzazu Barquín, Aleksandra Gentry‐Maharaj, C. Blake Gilks, Helena Gronwald, Marcel Grube, Paul R. Harnett, Holly R. Harris, Andreas D. Hartkopf, Arndt Hartmann, Alexander Hein, Joy Hendley, Brenda Y. Hernandez, Yajue Huang, Anna Jakubowska, Mercedes Jimenez‐Liñan, Michael E. Jones, Catherine J. Kennedy, Tomasz Kluz, Jennifer M. Koziak, Jaime Lesnock, Jenny Lester, Jan Lubiński, Teri A. Longacre, Maria Lycke, Constantina Mateoiu, Bryan M. McCauley, Valerie McGuire, Britta Ney, Alexander Olawaiye, Sandra Oršulić, Ana Osório, Luis Paz‐Ares, Teresa Ramón y Cajal, Joseph H. Rothstein, Matthias Ruebner, Minouk J. Schoemaker, Mitul Shah, Raghwa Sharma, Mark E. Sherman, Yurii B. Shvetsov, Naveena Singh, Helen Steed, Sarah J. Storr, Aline Talhouk, Nadia Traficante, Chen Wang, Alice S. Whittemore, Martin Widschwendter, Lynne R. Wilkens, Stacey J. Winham, Javier Benı́tez, Andrew Berchuck, David D.L. Bowtell, Francisco José Cândido dos Reis, Ian Campbell, Linda S. Cook, Anna DeFazio, Jennifer A. Doherty, Peter A. Fasching, Renée T. Fortner, María J. García, Marc T. Goodman, Ellen L. Goode, Jacek Gronwald, David G. Huntsman, Beth Y. Karlan, Linda E. Kelemen, Stefan Kommoss, Nhu D. Le, Stewart G. Martin, Usha Menon, Francesmary Modugno, Paul D.P. Pharoah, Joellen M. Schildkraut, Weiva Sieh, Annette Staebler, Karin Sundfeldt, Anthony J. Swerdlow, Susan J. Ramus, James D. Brenton

Bibliographic record

VenueThe Journal of Pathology Clinical Research · 2023
Typearticle
Languageen
FieldMedicine
TopicOvarian cancer diagnosis and treatment
Canadian institutionsAlberta Health ServicesCanada's Michael Smith Genome Sciences CentreVancouver General HospitalUniversity of British ColumbiaBC Cancer AgencyFoothills Medical CentreUniversity of AlbertaUniversity of Calgary
FundersCilagMedical Research and Materiel CommandNational Center for Advancing Translational SciencesInstitute of Cancer ResearchBreast Cancer NowUniversity College LondonCancer Institute NSWPeter MacCallum FoundationNational Cancer InstituteInstituto de Salud Carlos IIICancer Council TasmaniaUniversity of CalgaryCancer Council VictoriaMedical Research CouncilAstraZenecaGenentechNational Institutes of HealthUCLH Biomedical Research CentreEisaiBundesministerium für Bildung und ForschungMinisterio de Economía y CompetitividadCanadian Institutes of Health ResearchSwedish Cancer FoundationOvarian Cancer AustraliaIpsenCancer AustraliaNational Institute for Health and Care ResearchBeiGeneVGH and UBC Hospital FoundationMinnesota Ovarian Cancer AllianceNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchU.S. Department of DefenseCancer Research UKCancer Council NSWAmerican Cancer SocietyCancer Council South AustraliaPomorski Uniwersytet Medyczny W SzczecinieDeutsches KrebsforschungszentrumFred C. and Katherine B. Andersen FoundationUniversity of CambridgeUniversity of PittsburghMayo Foundation for Medical Education and ResearchNational Health and Medical Research CouncilNational Center for Research ResourcesBC Cancer FoundationOak FoundationEuropean Regional Development FundConselho Nacional de Desenvolvimento Científico e TecnológicoCancer Research SocietyNIHR Cambridge Biomedical Research CentreSydney West Translational Cancer Research Centre
KeywordsSerous carcinomaOvarian carcinomaTissue microarrayHazard ratioImmunohistochemistryClear cell carcinomaSerous fluidCarcinomaOncologyInternal medicineOvarian cancerMedicineConfidence intervalPathologyCancerBiology

Abstract

fetched live from OpenAlex

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.

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)0.026
metaresearch head score (Gemma)0.003
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 score0.024
Threshold uncertainty score0.917

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0260.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.002
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.284
GPT teacher head0.542
Teacher spread0.258 · 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

Citations28
Published2023
Admission routes2
Has abstractyes

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