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Diagnostic and prog...
Diagnostic and prognostic implications of a three-antibody molecular subtyping algorithm for non-muscle invasive bladder cancer
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- Jackson, Chelsea L. (författare)
- Queen's Cancer Research Institute
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- Chen, Lina (författare)
- Queen's University at Kingston
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- Hardy, Céline S.C. (författare)
- Queen's Cancer Research Institute
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- Ren, Kevin Y.M. (författare)
- Queen's University at Kingston
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- Visram, Kash (författare)
- Queen's Cancer Research Institute
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- Bratti, Vanessa F. (författare)
- Queen's Cancer Research Institute
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- Johnstone, Jeannette (författare)
- Queen's Cancer Research Institute
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- Sjödahl, Gottfrid (författare)
- Lund University,Lunds universitet,Urologi - blåscancer, Malmö,Forskargrupper vid Lunds universitet,Genomiska analyser av urinblåscancer,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urinblåsecancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Urology - urothelial cancer, Malmö,Lund University Research Groups,Urothelial Cancer Genomics,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Urothelial cancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Siemens, David Robert (författare)
- Queen's Cancer Research Institute
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- Gooding, Robert J. (författare)
- Queen's Cancer Research Institute
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- Berman, David M (författare)
- Queen's Cancer Research Institute
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(creator_code:org_t)
- 2021-10-26
- 2022
- Engelska.
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Ingår i: Journal of Pathology: Clinical Research. - : Wiley. - 2056-4538. ; 8:2, s. 143-154
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Abstract
Ämnesord
Stäng
- Intrinsic molecular subtypes may explain marked variation between bladder cancer patients in prognosis and response to therapy. Complex testing algorithms and little attention to more prevalent, early-stage (non-muscle invasive) bladder cancers (NMIBCs) have hindered implementation of subtyping in clinical practice. Here, using a three-antibody immunohistochemistry (IHC) algorithm, we identify the diagnostic and prognostic associations of well-validated proteomic features of basal and luminal subtypes in NMIBC. By IHC, we divided 481 NMIBCs into basal (GATA3−/KRT5+) and luminal (GATA3+/KRT5 variable) subtypes. We further divided the luminal subtype into URO (p16 low), URO-KRT5+ (KRT5+), and genomically unstable (GU) (p16 high) subtypes. Expression thresholds were confirmed using unsupervised hierarchical clustering. Subtypes were correlated with pathology and outcomes. All NMIBC cases clustered into the basal/squamous (basal) or one of the three luminal (URO, URO-KRT5+, and GU) subtypes. Although uncommon in this NMIBC cohort, basal tumors (3%, n = 16) had dramatically higher grade (100%, n = 16, odds ratio [OR] = 13, relative risk = 3.25) and stage, and rapid progression to muscle invasion (median progression-free survival = 35.4 months, p = 0.0001). URO, the most common subtype (46%, n = 220), showed rapid recurrence (median recurrence-free survival [RFS] = 11.5 months, p = 0.039) compared to its GU counterpart (29%, n = 137, median RFS = 16.9 months), even in patients who received intravesical immunotherapy (p = 0.049). URO-KRT5+ tumors (22%, n = 108) were typically low grade (66%, n = 71, OR = 3.7) and recurred slowly (median RFS = 38.7 months). Therefore, a simple immunohistochemical algorithm can identify clinically relevant molecular subtypes of NMIBC. In routine clinical practice, this three-antibody algorithm may help clarify diagnostic dilemmas and optimize surveillance and treatment strategies for patients.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- bladder cancer
- GATA3
- immunohistochemistry
- KRT5
- p16
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Jackson, Chelsea ...
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Chen, Lina
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Hardy, Céline S. ...
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Ren, Kevin Y.M.
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Visram, Kash
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Bratti, Vanessa ...
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visa fler...
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Johnstone, Jeann ...
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Sjödahl, Gottfri ...
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Siemens, David R ...
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Gooding, Robert ...
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Berman, David M
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
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Journal of Patho ...
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Lunds universitet