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Tytuł pozycji:

Intratumoral heterogeneity of surrogate molecular subtypes in urothelial carcinoma in situ of the urinary bladder: implications for prognostic stratification of high-risk non-muscle-invasive bladder cancer.

Tytuł:
Intratumoral heterogeneity of surrogate molecular subtypes in urothelial carcinoma in situ of the urinary bladder: implications for prognostic stratification of high-risk non-muscle-invasive bladder cancer.
Autorzy:
Garczyk S; Institute of Pathology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. .
Bischoff F; Institute of Pathology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
Schneider U; Institute of Pathology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
Golz R; Institute of Pathology, Helios University Hospital Wuppertal, Wuppertal, Germany.
von Rundstedt FC; Department of Urology, Helios University Hospital Wuppertal, Wuppertal, Germany.
Knüchel R; Institute of Pathology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
Degener S; Department of Urology, Helios University Hospital Wuppertal, Wuppertal, Germany.
Źródło:
Virchows Archiv : an international journal of pathology [Virchows Arch] 2021 Aug; Vol. 479 (2), pp. 325-335. Date of Electronic Publication: 2021 Mar 01.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Berlin ; New York : Springer International, c1994-
MeSH Terms:
Immunohistochemistry*
Biomarkers, Tumor/*analysis
Carcinoma in Situ/*chemistry
Urinary Bladder Neoplasms/*chemistry
Urothelium/*chemistry
Adult ; Age Factors ; Aged ; Aged, 80 and over ; Carcinoma in Situ/mortality ; Carcinoma in Situ/pathology ; Carcinoma in Situ/therapy ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Predictive Value of Tests ; Progression-Free Survival ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Smoking/adverse effects ; Tissue Array Analysis ; Urinary Bladder Neoplasms/mortality ; Urinary Bladder Neoplasms/pathology ; Urinary Bladder Neoplasms/therapy ; Urothelium/pathology
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Contributed Indexing:
Keywords: Bladder cancer; CIS; Carcinoma in situ; Intratumoral heterogeneity; Molecular subtypes; NMIBC
Substance Nomenclature:
0 (Biomarkers, Tumor)
Entry Date(s):
Date Created: 20210302 Date Completed: 20210909 Latest Revision: 20220218
Update Code:
20240105
PubMed Central ID:
PMC8364543
DOI:
10.1007/s00428-021-03054-0
PMID:
33650041
Czasopismo naukowe
Reliable factors predicting the disease course of non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) are unavailable. Molecular subtypes have potential for prognostic stratification of muscle-invasive bladder cancer, while their value for CIS patients is unknown. Here, the prognostic impact of both clinico-pathological parameters, including CIS focality, and immunohistochemistry-based surrogate subtypes was analyzed in a cohort of high-risk NMIBC patients with CIS. In 128 high-risk NMIBC patients with CIS, luminal (KRT20, GATA3, ERBB2) and basal (KRT5/6, KRT14) surrogate markers as well as p53 were analyzed in 213-231 biopsies. To study inter-lesional heterogeneity of CIS, marker expression in independent CIS biopsies from different bladder localizations was analyzed. Clinico-pathological parameters and surrogate subtypes were correlated with recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Forty-six and 30% of CIS patients exhibited a luminal-like (KRT20-positive, KRT5/6-negative) and a null phenotype (KRT20-negative, KRT5/6-negative), respectively. A basal-like subtype (KRT20-negative, KRT5/6-positive) was not observed. A significant degree of inter-lesional CIS heterogeneity was noted, reflected by 23% of patients showing a mixed subtype. Neither CIS surrogate subtype nor CIS focality was associated with patient outcome. Patient age and smoking status were the only potentially independent prognostic factors predicting RFS, PFS, OS, and PFS, respectively. In conclusion, further clarification of heterogeneity of surrogate subtypes in HR NMIBC and their prognostic value is of importance with regard to potential implementation of molecular subtyping into clinical routine. The potential prognostic usefulness of patient age and smoking status for high-risk NMIBC patients with CIS needs further validation.
(© 2021. The Author(s).)

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