Alignment of stroma fibers, microvessel density and immune cell populations determine overall survival in pancreatic cancer-An analysis of stromal morphology
Alignment of stroma fibers, microvessel density and immune cell populations determine overall survival in pancreatic cancer-An analysis of stromal morphology
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DOI：
10.1371/journal.pone.0234568
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发表时间：
2020-07-13
期刊：
影响因子：
3.7
通讯作者：
Wellner, Ulrich F.
中科院分区：
文献类型：
--
作者：
Bolm, Louisa;Zghurskyi, Petro;Wellner, Ulrich F.
本研究的目的是通过分析间质成分来定义组织形态学间质特征，并评估其对胰腺导管腺癌（PDAC）局部和全身肿瘤扩散和总生存的影响。方法和材料从前瞻性维护的数据库中确定接受肿瘤切除术的PDAC患者。重新评估组织学标本的基质形态特征，如基质纤维、成纤维细胞形态、基质密度、微血管密度和免疫细胞群分布。结果2011-2016年共发现108例PDAC患者行根治性切除术。间质纤维平行排列33例（30.6%），间质纤维随机排列75例（69.4%）。与平行排列相比，间质纤维的随机方向与较大的肿瘤大小（中位数3.62 cm对中位数2.87cm, p = 0.037）、淋巴结阳性疾病（76.0%对54.5%,p = 0.040）、较高的切缘阳性切除率（41.9%对15.2%,p = 0.008）以及较高的T3/4肿瘤发生率（33.3%对15.2%,p = 0.064）相关。在单变量分析中，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的总生存率更高（42个月vs 22个月，p = 0.046）。基质纤维的随机方向和微血管密度低的组合与总生存率受损相关（16个月对36个月，p = 0.019）。CD4/CD3比值高（16个月对33个月，p = 0.040）和CD163阳性细胞间质密度高与总生存率降低相关（27个月对34个月，p = 0.039）。在多变量分析中，基质纤维的随机取向和低微血管密度（HR 1.592, 95%CI 1.098 ~ 2.733, p = 0.029）、高CD4/CD3比值（HR 2.044, 95%CI 1.203 ~ 3.508, p = 0.028）和高CD163阳性细胞密度（HR 1.596, 95%CI 1.367 ~ 1.968, p = 0.036）仍然是独立的预后因素。结论间质纤维排列和微血管密度是PDAC患者简单的组织形态学特征，可作为局部肿瘤进展、扩散和手术可切除性的替代标志，并决定预后。高CD4/CD3比值和CD163阳性细胞计数决定预后不良。
Introduction 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). Methods and materials 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. Results 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. Conclusion 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.