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18F‐fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma

Positron emission tomography is a useful technique for diagnosing lymph node (LN) metastasis. This study aimed to elucidate the association between fluorodeoxyglucose accumulation and the microenvironment in metastatic LNs in lung adenocarcinoma. We retrospectively analyzed 62 patients with surgical...

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Autores principales: Nomura, Kotaro, Nakai, Tokiko, Nishina, Yukino, Sakamoto, Naoya, Miyoshi, Tomohiro, Tane, Kenta, Samejima, Joji, Aokage, Keiju, Kojima, Motohiro, Sakashita, Shingo, Taki, Tetsuro, Miyazaki, Saori, Watanabe, Reiko, Suzuki, Kenji, Tsuboi, Masahiro, Ishii, Genichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990723/
https://www.ncbi.nlm.nih.gov/pubmed/35023268
http://dx.doi.org/10.1111/cas.15266
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author Nomura, Kotaro
Nakai, Tokiko
Nishina, Yukino
Sakamoto, Naoya
Miyoshi, Tomohiro
Tane, Kenta
Samejima, Joji
Aokage, Keiju
Kojima, Motohiro
Sakashita, Shingo
Taki, Tetsuro
Miyazaki, Saori
Watanabe, Reiko
Suzuki, Kenji
Tsuboi, Masahiro
Ishii, Genichiro
author_facet Nomura, Kotaro
Nakai, Tokiko
Nishina, Yukino
Sakamoto, Naoya
Miyoshi, Tomohiro
Tane, Kenta
Samejima, Joji
Aokage, Keiju
Kojima, Motohiro
Sakashita, Shingo
Taki, Tetsuro
Miyazaki, Saori
Watanabe, Reiko
Suzuki, Kenji
Tsuboi, Masahiro
Ishii, Genichiro
author_sort Nomura, Kotaro
collection PubMed
description Positron emission tomography is a useful technique for diagnosing lymph node (LN) metastasis. This study aimed to elucidate the association between fluorodeoxyglucose accumulation and the microenvironment in metastatic LNs in lung adenocarcinoma. We retrospectively analyzed 62 patients with surgically resected pathological N2 lung adenocarcinoma who underwent preoperative PET. The maximum standardized uptake value (SUV(max)) in the metastatic LNs was measured. Lymph node specimens were immunohistochemically analyzed for CD8(+), FoxP3(+), and CD79a(+) lymphocytes, CD204(+) tumor‐associated macrophages (TAMs), and alpha‐smooth muscle actin‐positive cancer‐associated fibroblasts (αSMA(+) CAFs). We compared the clinicopathologic and immunohistochemical characteristics between two groups with high and low LN SUV(max). Using novel 3D hybrid spheroid models, we investigated the change in invasiveness of cancer cells in the presence of CAFs. In the multivariate analyses, LN SUV(max) was an independent prognostic factor. The overall survival in the LN SUV(max) high group was significantly worse than in the low group (P = .034). In the LN SUV(max) high group, metastatic cancer cell invasion of extranodal tissue was more frequent (P = .005) and the number of CD204(+) TAMs and αSMA(+) CAFs in metastatic LNs was significantly higher than in the low group (P < .001 and P = .002, respectively). Hybrid spheroid models revealed that cancer cells coexisting with CAFs were more invasive than those without CAFs. Our results indicated a strong association between LN SUV(max) and poor prognosis in patients with N2 lung adenocarcinoma. Moreover, LN SUV(max) was suggested to be associated with the presence of tumor‐promoting stromal cells in metastatic LNs.
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spelling pubmed-89907232022-04-13 18F‐fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma Nomura, Kotaro Nakai, Tokiko Nishina, Yukino Sakamoto, Naoya Miyoshi, Tomohiro Tane, Kenta Samejima, Joji Aokage, Keiju Kojima, Motohiro Sakashita, Shingo Taki, Tetsuro Miyazaki, Saori Watanabe, Reiko Suzuki, Kenji Tsuboi, Masahiro Ishii, Genichiro Cancer Sci Original Articles Positron emission tomography is a useful technique for diagnosing lymph node (LN) metastasis. This study aimed to elucidate the association between fluorodeoxyglucose accumulation and the microenvironment in metastatic LNs in lung adenocarcinoma. We retrospectively analyzed 62 patients with surgically resected pathological N2 lung adenocarcinoma who underwent preoperative PET. The maximum standardized uptake value (SUV(max)) in the metastatic LNs was measured. Lymph node specimens were immunohistochemically analyzed for CD8(+), FoxP3(+), and CD79a(+) lymphocytes, CD204(+) tumor‐associated macrophages (TAMs), and alpha‐smooth muscle actin‐positive cancer‐associated fibroblasts (αSMA(+) CAFs). We compared the clinicopathologic and immunohistochemical characteristics between two groups with high and low LN SUV(max). Using novel 3D hybrid spheroid models, we investigated the change in invasiveness of cancer cells in the presence of CAFs. In the multivariate analyses, LN SUV(max) was an independent prognostic factor. The overall survival in the LN SUV(max) high group was significantly worse than in the low group (P = .034). In the LN SUV(max) high group, metastatic cancer cell invasion of extranodal tissue was more frequent (P = .005) and the number of CD204(+) TAMs and αSMA(+) CAFs in metastatic LNs was significantly higher than in the low group (P < .001 and P = .002, respectively). Hybrid spheroid models revealed that cancer cells coexisting with CAFs were more invasive than those without CAFs. Our results indicated a strong association between LN SUV(max) and poor prognosis in patients with N2 lung adenocarcinoma. Moreover, LN SUV(max) was suggested to be associated with the presence of tumor‐promoting stromal cells in metastatic LNs. John Wiley and Sons Inc. 2022-02-18 2022-04 /pmc/articles/PMC8990723/ /pubmed/35023268 http://dx.doi.org/10.1111/cas.15266 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Nomura, Kotaro
Nakai, Tokiko
Nishina, Yukino
Sakamoto, Naoya
Miyoshi, Tomohiro
Tane, Kenta
Samejima, Joji
Aokage, Keiju
Kojima, Motohiro
Sakashita, Shingo
Taki, Tetsuro
Miyazaki, Saori
Watanabe, Reiko
Suzuki, Kenji
Tsuboi, Masahiro
Ishii, Genichiro
18F‐fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma
title 18F‐fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma
title_full 18F‐fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma
title_fullStr 18F‐fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma
title_full_unstemmed 18F‐fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma
title_short 18F‐fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma
title_sort 18f‐fluorodeoxyglucose uptake in pet is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in n2 lung adenocarcinoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990723/
https://www.ncbi.nlm.nih.gov/pubmed/35023268
http://dx.doi.org/10.1111/cas.15266
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