Cargando…

Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification

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 uroth...

Descripción completa

Detalles Bibliográficos
Autores principales: Montes-Mojarro, Ivonne A., Hassas, Saki, Staehle, Sina, Sander, Philip, Harland, Niklas, Serna-Higuita, Lina Maria, Bonzheim, Irina, Bösmüller, Hans, Stenzl, Arnulf, Fend, Falko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330009/
https://www.ncbi.nlm.nih.gov/pubmed/35897708
http://dx.doi.org/10.3390/ijms23158133
_version_ 1784758056621441024
author Montes-Mojarro, Ivonne A.
Hassas, Saki
Staehle, Sina
Sander, Philip
Harland, Niklas
Serna-Higuita, Lina Maria
Bonzheim, Irina
Bösmüller, Hans
Stenzl, Arnulf
Fend, Falko
author_facet Montes-Mojarro, Ivonne A.
Hassas, Saki
Staehle, Sina
Sander, Philip
Harland, Niklas
Serna-Higuita, Lina Maria
Bonzheim, Irina
Bösmüller, Hans
Stenzl, Arnulf
Fend, Falko
author_sort Montes-Mojarro, Ivonne A.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9330009
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-93300092022-07-29 Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification Montes-Mojarro, Ivonne A. Hassas, Saki Staehle, Sina Sander, Philip Harland, Niklas Serna-Higuita, Lina Maria Bonzheim, Irina Bösmüller, Hans Stenzl, Arnulf Fend, Falko Int J Mol Sci Article 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. MDPI 2022-07-23 /pmc/articles/PMC9330009/ /pubmed/35897708 http://dx.doi.org/10.3390/ijms23158133 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Montes-Mojarro, Ivonne A.
Hassas, Saki
Staehle, Sina
Sander, Philip
Harland, Niklas
Serna-Higuita, Lina Maria
Bonzheim, Irina
Bösmüller, Hans
Stenzl, Arnulf
Fend, Falko
Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification
title Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification
title_full Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification
title_fullStr Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification
title_full_unstemmed Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification
title_short Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification
title_sort multiparametric classification of non-muscle invasive papillary urothelial neoplasms: combining morphological, phenotypical, and molecular features for improved risk stratification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330009/
https://www.ncbi.nlm.nih.gov/pubmed/35897708
http://dx.doi.org/10.3390/ijms23158133
work_keys_str_mv AT montesmojarroivonnea multiparametricclassificationofnonmuscleinvasivepapillaryurothelialneoplasmscombiningmorphologicalphenotypicalandmolecularfeaturesforimprovedriskstratification
AT hassassaki multiparametricclassificationofnonmuscleinvasivepapillaryurothelialneoplasmscombiningmorphologicalphenotypicalandmolecularfeaturesforimprovedriskstratification
AT staehlesina multiparametricclassificationofnonmuscleinvasivepapillaryurothelialneoplasmscombiningmorphologicalphenotypicalandmolecularfeaturesforimprovedriskstratification
AT sanderphilip multiparametricclassificationofnonmuscleinvasivepapillaryurothelialneoplasmscombiningmorphologicalphenotypicalandmolecularfeaturesforimprovedriskstratification
AT harlandniklas multiparametricclassificationofnonmuscleinvasivepapillaryurothelialneoplasmscombiningmorphologicalphenotypicalandmolecularfeaturesforimprovedriskstratification
AT sernahiguitalinamaria multiparametricclassificationofnonmuscleinvasivepapillaryurothelialneoplasmscombiningmorphologicalphenotypicalandmolecularfeaturesforimprovedriskstratification
AT bonzheimirina multiparametricclassificationofnonmuscleinvasivepapillaryurothelialneoplasmscombiningmorphologicalphenotypicalandmolecularfeaturesforimprovedriskstratification
AT bosmullerhans multiparametricclassificationofnonmuscleinvasivepapillaryurothelialneoplasmscombiningmorphologicalphenotypicalandmolecularfeaturesforimprovedriskstratification
AT stenzlarnulf multiparametricclassificationofnonmuscleinvasivepapillaryurothelialneoplasmscombiningmorphologicalphenotypicalandmolecularfeaturesforimprovedriskstratification
AT fendfalko multiparametricclassificationofnonmuscleinvasivepapillaryurothelialneoplasmscombiningmorphologicalphenotypicalandmolecularfeaturesforimprovedriskstratification