Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28991
タイトル
Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors
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内容記述

Abstract

Objective: The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs).

Background: The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that 5 genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear.

Methods: We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings.

Results: Kaplan-Meier analysis indicated that loss of TSC2 (n = 58) or PTEN (n = 37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n = 41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n = 31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1-66.9, P = 0.003) in G2 PNETs.

Conclusions: Loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior and clinical outcomes of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs. Loss of pairs in ATRX, TSC2, or PTEN would be useful for selecting the candidate for postoperative adjuvant therapy.

(医博甲744)

著者
著者 上村 淳
著者(ヨミ) ウエムラ ジュン
著者(別表記) Uemura Jun
掲載誌
Annals of surgery
掲載誌(別表記)
Ann Surg.
出版者
American Surgical Association
Lippincott, Williams & Wilkins
出版年月日
2019-10-09
ISSN
0003-4932
NCID
AA12431796
PMID
31599805
DOI
10.1097/SLA.0000000000003624
資料タイプ
学位論文
言語
英語
権利関係
This article is distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/).
"This is the Accepted Version of the following article: Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors; Annals of surgery; Volume Publish Ahead of Print (Octover 9, 2019 ) doi: 10.1097/SLA.0000000000003624, which has been published in final form at https://doi.org/10.1097/SLA.0000000000003624 . "
エンバーゴ期間満了。 / The Embergo period has expired.
博士論文(全文を含む)
学位授与番号
博甲第744号
学位授与年月日
2020-03-24
学位名
博士(医学)
学位授与機関
香川大学
区分
香川大学
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