Donizy Piotr, Pagacz Konrad, Marczuk Jakub, Fendler Wojciech, Maciejczyk Adam, Halon Agnieszka, Matkowski Rafal
Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland.
Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland.
Onco Targets Ther. 2018 Mar 14;11:1413-1422. doi: 10.2147/OTT.S151286. eCollection 2018.
FOXP1 is a pleiotropic protein that plays important roles in immune responses (B-cell development regulation and differentiation of monocyte), organ development (cardiac valves, lung, and esophagus), and neuronal development. Besides being the primary regulator of normal human tissue development, FOXP1 also plays a role in tumorigenesis. However, the potential value of FOXP1 expression in tumor prognosis remains controversial. FOXP1 expression was assessed in tumor cells (TCs) and stromal cells (SCs) of cutaneous melanomas with the aim of analyzing the associations between FOXP1 expression and clinicopathological characteristics. We believe this article to be the first report analyzing the correlations between FOXP1 expression and clinicopathological, as well as histological, characteristics in melanoma.
In total, 96 formalin-fixed, paraffin-embedded primary cutaneous melanoma tissue specimens were subjected to immunohistochemical analysis for FOXP1, and the results were correlated with classical clinicopathological features and patient survival.
FOXP1 overexpression in TCs was strongly associated with the presence of metastases in sentinel lymph nodes (=0.0003, OR=11.66) and positive status of regional lymph nodes (=0.0006, OR=22.15). In 96% (52 of 54) of patients presenting with low FOXP1 expression, no clinical or histopathological features of lymphatic dissemination were observed. However, thinner and nonulcerated tumors were reported to have increased numbers of FOXP1-positive SCs. In addition, a strong association was observed between FOXP1 upregulation in SCs and the absence of regional lymph node metastases. There was a significant correlation between FOXP1 upregulation in TCs and shorter cancer-specific overall survival (log-rank test, =0.0040) and disease-free survival (log-rank test, =0.0021). FOXP1 expression was confirmed in multivariate analysis as a factor that significantly unfavorably impacts prognosis in melanoma patients (HR=3.14, =0.0299, adjusted for age, Breslow thickness, and sex).
The findings from this study indicate that FOXP1 has a major role in melanoma progression, which makes it a candidate for molecular target-based cancer therapy.
FOXP1是一种多效性蛋白，在免疫反应（B细胞发育调控和单核细胞分化）、器官发育（心脏瓣膜、肺和食管）以及神经元发育中发挥重要作用。除了是正常人体组织发育的主要调节因子外，FOXP1在肿瘤发生中也起作用。然而，FOXP1表达在肿瘤预后中的潜在价值仍存在争议。评估皮肤黑色素瘤肿瘤细胞（TCs）和基质细胞（SCs）中的FOXP1表达，旨在分析FOXP1表达与临床病理特征之间的关联。我们认为本文是第一篇分析FOXP1表达与黑色素瘤临床病理及组织学特征之间相关性的报告。
总共96例福尔马林固定、石蜡包埋的原发性皮肤黑色素瘤组织标本进行了FOXP1免疫组化分析，结果与经典临床病理特征及患者生存情况相关。
TCs中FOXP1过表达与前哨淋巴结转移的存在显著相关（=0.0003，OR=11.66）以及区域淋巴结阳性状态（=0.0006，OR=22.15）。在96%（54例中的52例）FOXP1表达低的患者中，未观察到淋巴扩散的临床或组织病理学特征。然而，据报道较薄且无溃疡的肿瘤中FOXP1阳性SCs数量增加。此外，观察到SCs中FOXP1上调与无区域淋巴结转移之间存在强关联。TCs中FOXP1上调与较短的癌症特异性总生存期（对数秩检验，=0.0040）和无病生存期（对数秩检验，=0.0021）之间存在显著相关性。在多变量分析中，FOXP1表达被确认为对黑色素瘤患者预后有显著不利影响的因素（HR=3.14，=0.0299，根据年龄、Breslow厚度和性别进行调整）。
本研究结果表明FOXP1在黑色素瘤进展中起主要作用，这使其成为基于分子靶点的癌症治疗的候选对象。
