期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 15, 页码 -出版社
MDPI
DOI: 10.3390/ijms23158133
关键词
non-invasive low-grade papillary urothelial carcinoma; high-grade papillary urothelial carcinoma; urothelial neoplasm of low malignant potential; classification
资金
- DFG [40947457, GRK2543/I]
- University of Tuebingen Hospital
- Medical Faculty at the University of Tuebingen
This study aims to develop a multiparametric classification to distinguish low-grade and high-grade urothelial tumors by analyzing immunohistochemical stains and pathogenic mutations. Analysis of clinical and histological data revealed that PUN-LMP and LG-PUC belong to one cluster, while HG-PUC belongs to another cluster, providing guidance for clinical management.
Diagnosis and grading of non-invasive papillary urothelial tumors according to the current WHO classification poses some challenges for pathologists. The diagnostic reproducibility of separating low-grade and high-grade lesions is low, which impacts their clinical management. Whereas papillary urothelial neoplasms with low malignant potential (PUN-LMP) and low-grade papillary non-invasive carcinoma (LG-PUC) are comparable and show frequent local recurrence but rarely metastasize, high-grade papillary non-invasive carcinoma (HG-PUC) has a poor prognosis. The main objective of this work is to develop a multiparametric classification to unambiguously distinguish low-grade and high-grade tumors, considering immunohistochemical stains for p53, FGFR3, CK20, MIB-1, p16, p21 and p-HH3, and pathogenic mutations in TP53, FGFR3, TP53, ERCC2, PIK3CA, PTEN and STAG2. We reviewed and analyzed the clinical and histological data of 45 patients with a consensus diagnosis of PUN-LMP (n = 8), non-invasive LG-PUC (n = 23), and HG-PUC (n = 14). The proliferation index and mitotic count assessed with MIB-1 and P-HH3 staining, respectively correlated with grading and clinical behavior. Targeted sequencing confirmed frequent FGFR3 mutations in non-invasive papillary tumors and identified mutations in TP53 as high-risk. Cluster analysis of the different immunohistochemical and molecular parameters allowed a clear separation in two different clusters: cluster 1 corresponding to PUN-LMP and LG-PUC (low MIB-1 and mitotic count/FGFR3 and STAG2 mutations) and cluster 2, HG-PUC (high MIB-1 and mitosis count/CK20 +++ expression, FGFR3 WT and TP53 mutation). Further analysis is required to validate and analyze the reproducibility of these clusters and their biological and clinical implication.
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