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Progression of urothelial carcinoma in situ of the urinary bladder: a switch from luminal to basal phenotype and related therapeutic implications.
- Source :
-
Virchows Archiv : an international journal of pathology [Virchows Arch] 2018 May; Vol. 472 (5), pp. 749-758. Date of Electronic Publication: 2018 Apr 13. - Publication Year :
- 2018
-
Abstract
- The stratification of bladder cancer into luminal and basal tumors has recently been introduced as a novel prognostic system in patient cohorts of muscle-invasive bladder cancer or high-grade papillary carcinomas. Using a representative immunohistochemistry panel, we analyzed luminal and basal marker expression in a large case series (n = 156) of urothelial carcinoma in situ (CIS), a precancerous lesion that frequently progresses to muscle-invasive disease. The majority of CIS cases was characterized by a positivity for luminal markers (aberrant cytokeratin (CK) 20 85% (132/156), GATA3 median Remmele score (score of staining intensity (0-3) multiplied with percentage of positive cells (0-4)): 12, estrogen receptor (ER) β Remmele score > 2: 88% (138/156), human epidermal growth factor receptor 2 (Her2) Dako score 3+ 32% (50/156), Her2 Dako score 2+ 33% (51/156)), and marginal expression of basal markers (CK5/6+ 2% (3/156), CK14+ 1% (2/156)). To further investigate phenotypic stability during disease progression, we compared 48 pairs of CIS and invasive tumors from the same biopsy. A highly significant loss of luminal marker expression (p < 0.001) was observed in the course of progression whereas an increase of basal marker expression (p < 0.01) was noted in the invasive compartment. Importantly, 91% of CIS cases demonstrated a positivity for at least one of the two predictive markers Her2 and ERβ, indicating that the analysis of Her2 and ERβ may help to identify CIS-patient subgroups prone to more efficient targeted treatment strategies. Larger prospective and biomarker-embedded clinical trials are needed to confirm and validate our preliminary findings.
- Subjects :
- Adult
Aged
Aged, 80 and over
Carcinoma in Situ classification
Carcinoma, Transitional Cell classification
Disease Progression
Female
Humans
Male
Middle Aged
Phenotype
Prospective Studies
Urinary Bladder Neoplasms classification
Biomarkers, Tumor analysis
Carcinoma in Situ pathology
Carcinoma, Transitional Cell pathology
Urinary Bladder Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-2307
- Volume :
- 472
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Virchows Archiv : an international journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 29654370
- Full Text :
- https://doi.org/10.1007/s00428-018-2354-9