%0 Journal Article %1 ijms23158133 %A Montes-Mojarro, Ivonne A. %A Hassas, Saki %A Staehle, Sina %A Sander, Philip %A Harland, Niklas %A Serna-Higuita, Lina Maria %A Bonzheim, Irina %A Bösmüller, Hans %A Stenzl, Arnulf %A Fend, Falko %D 2022 %J International Journal of Molecular Sciences %K arnulf_stenzl falko_fend grk2543 hans_boesmueller ivonne_montes-mojarro journal niklas_harland reviewed saki_hassas sina_staehle %N 15 %R 10.3390/ijms23158133 %T Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification %U https://www.mdpi.com/1422-0067/23/15/8133 %V 23 %X 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.

@article{ijms23158133, abstract = {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.}, added-at = {2023-06-27T06:34:49.000+0200}, article-number = {8133}, author = {Montes-Mojarro, Ivonne A. and Hassas, Saki and Staehle, Sina and Sander, Philip and Harland, Niklas and Serna-Higuita, Lina Maria and Bonzheim, Irina and Bösmüller, Hans and Stenzl, Arnulf and Fend, Falko}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/20e1a3e0320180a27a5f84daf06aba687/ffischer}, doi = {10.3390/ijms23158133}, interhash = {2461f184db71d1d9298d737bdae2e30f}, intrahash = {0e1a3e0320180a27a5f84daf06aba687}, issn = {1422-0067}, journal = {International Journal of Molecular Sciences}, keywords = {arnulf_stenzl falko_fend grk2543 hans_boesmueller ivonne_montes-mojarro journal niklas_harland reviewed saki_hassas sina_staehle}, number = 15, pubmedid = {35897708}, timestamp = {2023-08-10T10:14:20.000+0200}, title = {Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification}, url = {https://www.mdpi.com/1422-0067/23/15/8133}, volume = 23, year = 2022 }