Department of Surgery, University Medical Center Luebeck, Luebeck, Germany.
Department of General Surgery #1, Bogomolets National Medical University, Kyiv, Ukraine.
PLoS One. 2020 Jul 13;15(7):e0234568. doi: 10.1371/journal.pone.0234568. eCollection 2020.
The aim of this study was to define histo-morphological stroma characteristics by analyzing stromal components, and to evaluate their impact on local and systemic tumor spread and overall survival in pancreatic ductal adenocarcinoma (PDAC).
Patients who underwent oncologic resections with curative intent for PDAC were identified from a prospectively maintained database. Histological specimens were re-evaluated for morphological stroma features as stromal fibers, fibroblast morphology, stroma matrix density, microvessel density and distribution of immune cell populations.
A total of 108 patients were identified undergoing curative resection for PDAC in the period from 2011-2016. 33 (30.6%) patients showed parallel alignment of stroma fibers while 75 (69.4%) had randomly oriented stroma fibers. As compared to parallel alignment, random orientation of stroma fibers was associated with larger tumor size (median 3.62 cm vs. median 2.87cm, p = 0.037), nodal positive disease (76.0% vs. 54.5%, p = 0.040), higher margin positive resection rates (41.9% vs. 15.2%, p = 0.008) and a trend for higher rates of T3/4 tumors (33.3% vs. 15.2%, p = 0.064). In univariate analysis, patients with parallel alignment of stroma fibers had improved overall survival rates as compared to patients with random orientation of stroma fibers (42 months vs. 22 months, p = 0.046). The combination of random orientation of stroma fibers and low microvessel density was associated with impaired overall survival rates (16 months vs. 36 months, p = 0.019). A high CD4/CD3 ratio (16 months vs. 33 months, p = 0.040) and high stromal density of CD163 positive cells were associated with reduced overall survival (27 months vs. 34 months, p = 0.039). In multivariable analysis, the combination of random orientation of stroma fibers and low microvessel density (HR 1.592, 95%CI 1.098-2.733, p = 0.029), high CD4/CD3 ratio (HR 2.044, 95%CI 1.203-3.508, p = 0.028) and high density of CD163 positive cells (HR 1.596, 95%CI 1.367-1.968, p = 0.036) remained independent prognostic factors.
Alignment of stroma fibers and microvessel density are simple histomorphological features serving as surrogate markers of local tumor progression dissemination and surgical resectability and determine prognosis in PDAC patients. High CD4/CD3 ratio and CD163 positive cell counts determine poor prognosis.
本研究旨在通过分析肿瘤基质成分来定义组织形态学基质特征，并评估其对胰腺导管腺癌（PDAC）局部和全身肿瘤扩散以及总生存的影响。
从一个前瞻性维护的数据库中确定了接受根治性切除术治疗 PDAC 的患者。对组织学标本进行了重新评估，以评估形态学基质特征，包括基质纤维、成纤维细胞形态、基质基质密度、微血管密度和免疫细胞群体分布。
在 2011-2016 年期间，共确定了 108 例接受根治性切除术治疗 PDAC 的患者。33 例（30.6%）患者的基质纤维呈平行排列，75 例（69.4%）患者的基质纤维呈随机排列。与平行排列相比，基质纤维的随机排列与更大的肿瘤大小（中位数 3.62cm 与中位数 2.87cm，p=0.037）、阳性淋巴结疾病（76.0%与 54.5%，p=0.040）、更高的边缘阳性切除率（41.9%与 15.2%，p=0.008）和更高的 T3/4 肿瘤发生率趋势（33.3%与 15.2%，p=0.064）相关。在单因素分析中，与基质纤维随机排列的患者相比，基质纤维平行排列的患者总生存率更高（42 个月与 22 个月，p=0.046）。基质纤维随机排列和低微血管密度的组合与总生存率降低相关（16 个月与 36 个月，p=0.019）。CD4/CD3 比值高（16 个月与 33 个月，p=0.040）和 CD163 阳性细胞基质密度高与总生存率降低相关（27 个月与 34 个月，p=0.039）。在多因素分析中，基质纤维随机排列和低微血管密度的组合（HR 1.592，95%CI 1.098-2.733，p=0.029）、CD4/CD3 比值高（HR 2.044，95%CI 1.203-3.508，p=0.028）和 CD163 阳性细胞密度高（HR 1.596，95%CI 1.367-1.968，p=0.036）仍然是独立的预后因素。
基质纤维的排列和微血管密度是简单的组织形态学特征，可作为局部肿瘤进展和扩散以及手术可切除性的替代标志物，并确定 PDAC 患者的预后。CD4/CD3 比值和 CD163 阳性细胞计数高预示预后不良。
