Patsouras Dimitrios, Papaxoinis Kostis, Kostakis Alkiviadis, Safioleas Michael C, Lazaris Andreas C, Nicolopoulou-Stamati Polyxeni
Department of GI Surgery, St. Thomas' Hospital, London SE1 7EH, United Kingdom.
Gastroenterology Unit, 1st Department of Internal Medicine‑Propaedeutic, 'Laiko' General Hospital, Athens University Medical School, Athens GR‑11527, Greece.
Mol Med Rep. 2015 Jun;11(6):4585-90. doi: 10.3892/mmr.2015.3259. Epub 2015 Jan 27.
Fibroblast activation protein (FAP), a selective protein for tumor stromal fibroblasts, is expressed in >90% of human epithelial carcinomas. A characteristic feature of pancreatic cancer is an extensive fibrotic or desmoplastic reaction surrounding the primary tumor. The present study aimed to evaluate the expression levels of FAP and vascular endothelial growth factor (VEGF) and determine their correlation in pancreatic adenocarcinoma. Confocal laser scanning microscopy and conventional immunohistochemical analysis were used to quantify FAP and VEGF expression levels in formalin‑fixed and paraffin‑embedded tissue biopsies from 46 patients (male, 26; female, 20; mean age, 66 years; age range, 53‑80 years) with pancreatic adenocarcinoma stage IIA or IIB. The expression levels of FAP in the neoplastic and adjacent normal tissue were significantly higher in stage IIB patients, compared with stage IIA patients. FAP expression was correlated with positive lymph nodes, resulting in poor prognosis for stage IIB patients. The partial correlation coefficient between FAP and VEGF expression levels was 0.39 (P=0.007), and the two factors had an effect on patient survival. Multivariate analysis demonstrated the prognostic superiority of FAP over VEGF, which is considered to be the most consistently reproducible molecular marker with prognostic value in resected pancreatic adenocarcinoma. Due to the limited beneficial effect of current systemic therapies for pancreatic adenocarcinoma, targeting FAP may be a potential therapeutic strategy and requires further investigation.
成纤维细胞活化蛋白(FAP)是一种肿瘤基质成纤维细胞的选择性蛋白,在90%以上的人类上皮癌中表达。胰腺癌的一个特征是在原发性肿瘤周围存在广泛的纤维化或促结缔组织增生反应。本研究旨在评估FAP和血管内皮生长因子(VEGF)的表达水平,并确定它们在胰腺腺癌中的相关性。采用共聚焦激光扫描显微镜和传统免疫组织化学分析方法,对46例(男性26例,女性20例;平均年龄66岁,年龄范围53 - 80岁)IIA期或IIB期胰腺腺癌患者的福尔马林固定石蜡包埋组织活检标本中FAP和VEGF的表达水平进行定量分析。与IIA期患者相比,IIB期患者肿瘤组织和邻近正常组织中FAP的表达水平显著更高。FAP表达与阳性淋巴结相关,导致IIB期患者预后不良。FAP和VEGF表达水平之间的偏相关系数为0.39(P = 0.007),这两个因素对患者生存有影响。多变量分析显示FAP在预后方面优于VEGF,VEGF被认为是在切除的胰腺腺癌中最具一致性且可重复的具有预后价值的分子标志物。由于目前针对胰腺腺癌的全身治疗效果有限,靶向FAP可能是一种潜在的治疗策略,需要进一步研究。