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Enhanced Angiogenesis in Salivary Duct Carcinoma Ex-Pleomorphic Adenoma

Salivary duct carcinoma (SDC) is morphologically similar to breast cancer, with HER2-overexpression reported. With regard to the pattern of disease onset, SDC can arise from de novo or carcinoma ex-pleomorphic adenoma (Ca-ex-PA). Recently, multiple molecular profiles of SDC as well as breast cancer...

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Autores principales: Suzuki, Takayoshi, Kano, Satoshi, Suzuki, Masanobu, Yasukawa, Shinichiro, Mizumachi, Takatsugu, Tsushima, Nayuta, Hatanaka, Kanako C., Hatanaka, Yutaka, Matsuno, Yoshihiro, Homma, Akihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937931/
https://www.ncbi.nlm.nih.gov/pubmed/33692941
http://dx.doi.org/10.3389/fonc.2020.603717
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author Suzuki, Takayoshi
Kano, Satoshi
Suzuki, Masanobu
Yasukawa, Shinichiro
Mizumachi, Takatsugu
Tsushima, Nayuta
Hatanaka, Kanako C.
Hatanaka, Yutaka
Matsuno, Yoshihiro
Homma, Akihiro
author_facet Suzuki, Takayoshi
Kano, Satoshi
Suzuki, Masanobu
Yasukawa, Shinichiro
Mizumachi, Takatsugu
Tsushima, Nayuta
Hatanaka, Kanako C.
Hatanaka, Yutaka
Matsuno, Yoshihiro
Homma, Akihiro
author_sort Suzuki, Takayoshi
collection PubMed
description Salivary duct carcinoma (SDC) is morphologically similar to breast cancer, with HER2-overexpression reported. With regard to the pattern of disease onset, SDC can arise from de novo or carcinoma ex-pleomorphic adenoma (Ca-ex-PA). Recently, multiple molecular profiles of SDC as well as breast cancer have been reported, with significant differences in HER2 expression between Ca-ex-PA and de novo. We assessed the differences in gene expression between onset classifications. We conducted immunohistochemical analysis and HER2-DISH for 23 patients and classified SDCs into three subtypes as follows: “HER2-positive” (HER2+/any AR), “Luminal-AR” (HER2-/AR+), and “Basal-like” (HER2-/AR-). We assessed the expression levels of 84 functional genes for 19 patients by using a qRT-PCR array. Ten cases were classified as HER2-positive, seven cases as Luminal-AR, and six cases as Basal-like. The gene expression pattern was generally consistent with the corresponding immunostaining classification. The expression levels of VEGFA, ERBB2(HER2), IGF1R, RB1, and XBP1 were higher, while those of SLIT2 and PTEN were lower in Ca-ex-PA than in de novo. The functions of those genes were concentrated in angiogenesis and AKT/PI3K signaling pathway (Fisher’s test: p-value = 0.025 and 0.004, respectively). Multiple machine learning methods, OPLS-DA, LASSO, and RandomForest, also show that VEGFA can be a candidate for the characteristic differences between Ca-ex-PA and de novo. In conclusion, the AKT/PI3K signaling pathway leading to angiogenesis was hyper-activated in all SDCs, particularly in those classified into the Ca-ex-PAs. VEGFA was over-expressed significantly in the Ca-ex-PA, which can be a crucial factor in the malignant conversion to SDC.
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spelling pubmed-79379312021-03-09 Enhanced Angiogenesis in Salivary Duct Carcinoma Ex-Pleomorphic Adenoma Suzuki, Takayoshi Kano, Satoshi Suzuki, Masanobu Yasukawa, Shinichiro Mizumachi, Takatsugu Tsushima, Nayuta Hatanaka, Kanako C. Hatanaka, Yutaka Matsuno, Yoshihiro Homma, Akihiro Front Oncol Oncology Salivary duct carcinoma (SDC) is morphologically similar to breast cancer, with HER2-overexpression reported. With regard to the pattern of disease onset, SDC can arise from de novo or carcinoma ex-pleomorphic adenoma (Ca-ex-PA). Recently, multiple molecular profiles of SDC as well as breast cancer have been reported, with significant differences in HER2 expression between Ca-ex-PA and de novo. We assessed the differences in gene expression between onset classifications. We conducted immunohistochemical analysis and HER2-DISH for 23 patients and classified SDCs into three subtypes as follows: “HER2-positive” (HER2+/any AR), “Luminal-AR” (HER2-/AR+), and “Basal-like” (HER2-/AR-). We assessed the expression levels of 84 functional genes for 19 patients by using a qRT-PCR array. Ten cases were classified as HER2-positive, seven cases as Luminal-AR, and six cases as Basal-like. The gene expression pattern was generally consistent with the corresponding immunostaining classification. The expression levels of VEGFA, ERBB2(HER2), IGF1R, RB1, and XBP1 were higher, while those of SLIT2 and PTEN were lower in Ca-ex-PA than in de novo. The functions of those genes were concentrated in angiogenesis and AKT/PI3K signaling pathway (Fisher’s test: p-value = 0.025 and 0.004, respectively). Multiple machine learning methods, OPLS-DA, LASSO, and RandomForest, also show that VEGFA can be a candidate for the characteristic differences between Ca-ex-PA and de novo. In conclusion, the AKT/PI3K signaling pathway leading to angiogenesis was hyper-activated in all SDCs, particularly in those classified into the Ca-ex-PAs. VEGFA was over-expressed significantly in the Ca-ex-PA, which can be a crucial factor in the malignant conversion to SDC. Frontiers Media S.A. 2021-02-22 /pmc/articles/PMC7937931/ /pubmed/33692941 http://dx.doi.org/10.3389/fonc.2020.603717 Text en Copyright © 2021 Suzuki, Kano, Suzuki, Yasukawa, Mizumachi, Tsushima, Hatanaka, Hatanaka, Matsuno and Homma http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Suzuki, Takayoshi
Kano, Satoshi
Suzuki, Masanobu
Yasukawa, Shinichiro
Mizumachi, Takatsugu
Tsushima, Nayuta
Hatanaka, Kanako C.
Hatanaka, Yutaka
Matsuno, Yoshihiro
Homma, Akihiro
Enhanced Angiogenesis in Salivary Duct Carcinoma Ex-Pleomorphic Adenoma
title Enhanced Angiogenesis in Salivary Duct Carcinoma Ex-Pleomorphic Adenoma
title_full Enhanced Angiogenesis in Salivary Duct Carcinoma Ex-Pleomorphic Adenoma
title_fullStr Enhanced Angiogenesis in Salivary Duct Carcinoma Ex-Pleomorphic Adenoma
title_full_unstemmed Enhanced Angiogenesis in Salivary Duct Carcinoma Ex-Pleomorphic Adenoma
title_short Enhanced Angiogenesis in Salivary Duct Carcinoma Ex-Pleomorphic Adenoma
title_sort enhanced angiogenesis in salivary duct carcinoma ex-pleomorphic adenoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937931/
https://www.ncbi.nlm.nih.gov/pubmed/33692941
http://dx.doi.org/10.3389/fonc.2020.603717
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