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Histologic Spectrum of Polymorphous Adenocarcinoma of the Salivary Gland Harbor Genetic Alterations Affecting PRKD Genes
Polymorphous adenocarcinoma (PAC) and cribriform adenocarcinoma of (minor) salivary gland (CASG) are salivary gland tumors with overlapping spectrum of morphology. Whether these represent distinct entities or a histologic spectrum of the same tumor remains contentious. PACs harbor recurrent PRKD1 E7...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930326/ https://www.ncbi.nlm.nih.gov/pubmed/31492931 http://dx.doi.org/10.1038/s41379-019-0351-4 |
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author | Sebastiao, Ana Paula Martins Xu, Bin Lozada, John R Pareja, Fresia Geyer, Felipe C Da Cruz Paula, Arnaud da Silva, Edaise M. Ghossein, Ronald A. Weinreb, Ilan de Noronha, Lucia Weigelt, Britta Reis-Filho, Jorge S. Katabi, Nora |
author_facet | Sebastiao, Ana Paula Martins Xu, Bin Lozada, John R Pareja, Fresia Geyer, Felipe C Da Cruz Paula, Arnaud da Silva, Edaise M. Ghossein, Ronald A. Weinreb, Ilan de Noronha, Lucia Weigelt, Britta Reis-Filho, Jorge S. Katabi, Nora |
author_sort | Sebastiao, Ana Paula Martins |
collection | PubMed |
description | Polymorphous adenocarcinoma (PAC) and cribriform adenocarcinoma of (minor) salivary gland (CASG) are salivary gland tumors with overlapping spectrum of morphology. Whether these represent distinct entities or a histologic spectrum of the same tumor remains contentious. PACs harbor recurrent PRKD1 E710D hotspot mutations in >70% of cases, whereas 80% of CASGs display rearrangements involving PRKD1, PRKD2 or PRKD3 (PRKD1/2/3). We studied the molecular and morphologic features of 37 PACs/CASGs, seeking to identify the associations among genotype, histologic phenotype and classification. DNA was subjected to Sanger sequencing analysis of the PRKD1 hotspot locus. Fluorescence in situ hybridization (FISH) analysis for PRKD1/2/3 was performed using dual-color break-apart probes. Tumors were classified into four categories as described previously: PAC, CASG, tumor with indeterminate features (TIF) and tumor with a predominant papillary pattern (TPPP). PRKD1 E710D hotspot mutations were identified in 56%, 20%, 43% and 0% of PACs, CASGs, TIFs, and TPPPs, respectively. FISH demonstrated PRKD1/2/3 rearrangements in 13%, 78%, 36% and 75% of PACs, CASGs, TIFs and TPPPs, respectively. Histologically, fusion-positive tumors were associated with a high percentage of papillary growth, low percentage of single filing arrangement, a propensity of base of tongue location, and frequent (50%) lymph node metastasis, compared with the mutation-related tumors which had negligible nodal metastasis risk. Our results demonstrated that 1) PACs/CASGs are underpinned by genetic alterations affecting PRKD genes; 2) despite the associations between PAC and PRKD1 hotspot mutations and CASG and PRKD1/2/3 fusion, such distinction is not absolute; and 3) there is of a novel genotypic-phenotypic association whereby fusion-positive tumors are usually located in the base of tongue, show papillary architecture and have a high risk of nodal metastasis. Genetic analysis of PRKD genes appears to be useful characterizing this spectrum of tumors, not only histologically but clinically identifying those tumors with high risk of nodal metastasis. |
format | Online Article Text |
id | pubmed-6930326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-69303262020-03-06 Histologic Spectrum of Polymorphous Adenocarcinoma of the Salivary Gland Harbor Genetic Alterations Affecting PRKD Genes Sebastiao, Ana Paula Martins Xu, Bin Lozada, John R Pareja, Fresia Geyer, Felipe C Da Cruz Paula, Arnaud da Silva, Edaise M. Ghossein, Ronald A. Weinreb, Ilan de Noronha, Lucia Weigelt, Britta Reis-Filho, Jorge S. Katabi, Nora Mod Pathol Article Polymorphous adenocarcinoma (PAC) and cribriform adenocarcinoma of (minor) salivary gland (CASG) are salivary gland tumors with overlapping spectrum of morphology. Whether these represent distinct entities or a histologic spectrum of the same tumor remains contentious. PACs harbor recurrent PRKD1 E710D hotspot mutations in >70% of cases, whereas 80% of CASGs display rearrangements involving PRKD1, PRKD2 or PRKD3 (PRKD1/2/3). We studied the molecular and morphologic features of 37 PACs/CASGs, seeking to identify the associations among genotype, histologic phenotype and classification. DNA was subjected to Sanger sequencing analysis of the PRKD1 hotspot locus. Fluorescence in situ hybridization (FISH) analysis for PRKD1/2/3 was performed using dual-color break-apart probes. Tumors were classified into four categories as described previously: PAC, CASG, tumor with indeterminate features (TIF) and tumor with a predominant papillary pattern (TPPP). PRKD1 E710D hotspot mutations were identified in 56%, 20%, 43% and 0% of PACs, CASGs, TIFs, and TPPPs, respectively. FISH demonstrated PRKD1/2/3 rearrangements in 13%, 78%, 36% and 75% of PACs, CASGs, TIFs and TPPPs, respectively. Histologically, fusion-positive tumors were associated with a high percentage of papillary growth, low percentage of single filing arrangement, a propensity of base of tongue location, and frequent (50%) lymph node metastasis, compared with the mutation-related tumors which had negligible nodal metastasis risk. Our results demonstrated that 1) PACs/CASGs are underpinned by genetic alterations affecting PRKD genes; 2) despite the associations between PAC and PRKD1 hotspot mutations and CASG and PRKD1/2/3 fusion, such distinction is not absolute; and 3) there is of a novel genotypic-phenotypic association whereby fusion-positive tumors are usually located in the base of tongue, show papillary architecture and have a high risk of nodal metastasis. Genetic analysis of PRKD genes appears to be useful characterizing this spectrum of tumors, not only histologically but clinically identifying those tumors with high risk of nodal metastasis. 2019-09-06 2020-01 /pmc/articles/PMC6930326/ /pubmed/31492931 http://dx.doi.org/10.1038/s41379-019-0351-4 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Sebastiao, Ana Paula Martins Xu, Bin Lozada, John R Pareja, Fresia Geyer, Felipe C Da Cruz Paula, Arnaud da Silva, Edaise M. Ghossein, Ronald A. Weinreb, Ilan de Noronha, Lucia Weigelt, Britta Reis-Filho, Jorge S. Katabi, Nora Histologic Spectrum of Polymorphous Adenocarcinoma of the Salivary Gland Harbor Genetic Alterations Affecting PRKD Genes |
title | Histologic Spectrum of Polymorphous Adenocarcinoma of the Salivary Gland Harbor Genetic Alterations Affecting PRKD Genes |
title_full | Histologic Spectrum of Polymorphous Adenocarcinoma of the Salivary Gland Harbor Genetic Alterations Affecting PRKD Genes |
title_fullStr | Histologic Spectrum of Polymorphous Adenocarcinoma of the Salivary Gland Harbor Genetic Alterations Affecting PRKD Genes |
title_full_unstemmed | Histologic Spectrum of Polymorphous Adenocarcinoma of the Salivary Gland Harbor Genetic Alterations Affecting PRKD Genes |
title_short | Histologic Spectrum of Polymorphous Adenocarcinoma of the Salivary Gland Harbor Genetic Alterations Affecting PRKD Genes |
title_sort | histologic spectrum of polymorphous adenocarcinoma of the salivary gland harbor genetic alterations affecting prkd genes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930326/ https://www.ncbi.nlm.nih.gov/pubmed/31492931 http://dx.doi.org/10.1038/s41379-019-0351-4 |
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