Reduction of intrapancreatic neural density in cancer tissue predicts poorer outcome in pancreatic ductal carcinoma
Reduction of intrapancreatic neural density in cancer tissue predicts poorer outcome in pancreatic ductal carcinoma
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DOI：
10.1111/cas.13975
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发表时间：
2019-04-01
期刊：
影响因子：
5.7
通讯作者：
Katai, Hitoshi
中科院分区：
文献类型：
--
作者：
Iwasaki, Toshimitsu;Hiraoka, Nobuyoshi;Katai, Hitoshi
神经侵袭是胰腺导管腺癌（PDAC）患者局部晚期和/或转移性疾病进展的恶性特征之一。关于PDAC组织中神经纤维的分布和状态及其临床病理影响的研究很少。本研究旨在探讨PDAC患者胰腺内神经改变的临床病理特征和预后价值。我们回顾性分析了256例接受宏观根治性手术的PDAC患者。用特异性神经标记物GAP-43免疫标记的神经纤维在PDAC、慢性胰腺炎（CP）和正常胰腺组织中进行数字计数和比较。CP和PDAC的小叶间神经纤维明显肥大，但PDAC的胰腺内神经密度和神经数量明显减少。它们倾向于向肿瘤中心减少。Kaplan-Meier生存分析显示，低神经密度与较短的总生存期（OS）之间存在统计学显著相关性（P=0.014），高神经浸润与较短的OS之间存在统计学显著相关性（P=0.017）。神经密度（P=0.04; HR=1.496; 95%CI 1.018-2.199）和神经浸润率（P=0.064; HR=1.439; 95%CI 0.980 ~ 2.114）是影响患者生存期的多因素分析。这些发现提示PDAC患者胰腺内神经密度低是一个独立的预测因子，可能代表肿瘤的侵袭性行为。此外，我们提出了一种简单，实用和可重复的方法（测量神经密度和神经侵袭率在传统的组织病理学诊断PDAC），这已被验证使用另一个队列（n=81）。
Neural invasion is one of the malignant features contributing to locally advanced and/or metastatic disease progression in patients with pancreatic ductal adenocarcinoma (PDAC). Few studies exist on the distribution and state of nerve fibers in PDAC tissue and their clinicopathological impacts. The aim of the present study was to investigate the clinicopathological characteristics and prognostic value of intrapancreatic neural alterations in patients with PDAC. We retrospectively analyzed 256 patients with PDAC who underwent macroscopic curative surgery. Nerve fibers, immunolabeled with a specific neural marker GAP-43, were digitally counted and compared among PDAC, chronic pancreatitis (CP) and normal pancreatic tissues. Interlobular nerve fibers were apparently hypertrophic in both CP and PDAC, although intrapancreatic neural density and nerve number decreased characteristically in PDAC. They tended to decrease toward the center of the tumor. Kaplan-Meier survival analyses revealed a statistically significant correlation between low neural density and shorter overall survival (OS) (P=0.014), and between high neural invasion and shorter OS (P=0.017). Neural density (P=0.04; HR=1.496; 95% CI 1.018-2.199) and neural invasion ratio (P=0.064; HR=1.439; 95% CI .980-2.114) were prognostic factors of shorter OS in the multivariate analysis. These findings suggest low intrapancreatic neural density in patients with PDAC as an independent prognosticator, which may represent aggressive tumor behavior. Furthermore, we propose a simple, practical and reproducible method (to measure neural density and the neural invasion ratio during conventional histopathological diagnosis of PDAC), which has been validated using another cohort (n=81).