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Upregulation of FOXP1 is a new independent unfavorable prognosticator and a specific predictor of lymphatic dissemination in cutaneous melanoma patients

Authors Donizy P, Pagacz K, Marczuk J, Fendler W, Maciejczyk A, Halon A, Matkowski R

Received 9 September 2017

Accepted for publication 5 December 2017

Published 14 March 2018 Volume 2018:11 Pages 1413—1422

DOI https://doi.org/10.2147/OTT.S151286

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Tohru Yamada


Piotr Donizy,1 Konrad Pagacz,2 Jakub Marczuk,1 Wojciech Fendler,2 Adam Maciejczyk,3,4 Agnieszka Halon,1 Rafal Matkowski4,5

1Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland; 2Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland; 3Department of Oncology and Clinic of Radiation Oncology, Wroclaw Medical University, Wroclaw, Poland; 4Lower Silesian Oncology Centre, Wroclaw, Poland; 5Department of Oncology and Division of Surgical Oncology, Wroclaw Medical University, Wroclaw, Poland


Background:
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.
Materials and methods: 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.
Results: FOXP1 overexpression in TCs was strongly associated with the presence of metastases in sentinel lymph nodes (p=0.0003, OR=11.66) and positive status of regional lymph nodes (p=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, p=0.0040) and disease-free survival (log-rank test, p=0.0021). FOXP1 expression was confirmed in multivariate analysis as a factor that significantly unfavorably impacts prognosis in melanoma patients (HR=3.14, p=0.0299, adjusted for age, Breslow thickness, and sex).
Conclusion: 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.

Keywords: dermatopathology, melanocytic lesion, microenvironment, tumor biology, melanomagenesis

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