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Forkhead Box C1 (FOXC1) Expression in Stromal Cells within the Microenvironment of T and NK Cell Lymphomas: Association with Tumor Dormancy and Activation

Authors
 Ji Hae Nahm  ;  Woo Ick Yang  ;  Sun Och Yoon 
Citation
 CANCER RESEARCH AND TREATMENT, Vol.52(4) : 1273-1282, 2020-10 
Journal Title
 CANCER RESEARCH AND TREATMENT 
ISSN
 1598-2998 
Issue Date
2020-10
Keywords
ERK ; FOXC1 ; T and NK cell lymphomas ; dormancy ; p38 ; stromal cells ; tumor microenvironment
Abstract
Purpose: Forkhead box C1 (FOXC1) is critical for maintaining bone marrow microenvironments during hematopoiesis, but its role in hematological malignancies remains obscure. Here, we investigated whether FOXC1 regulates tumor dormancy and activation in the microenvironments of T and natural killer (NK) cell lymphomas. Materials and methods: One hundred and twenty cases of T and NK cell lymphomas were included; the immunohistochemical expression of FOXC1 was investigated in stromal cells, and numbers of FOXC1+ stromal cells were counted. Furthermore, the expression of phosphorylated p38 (p-p38) and phosphorylated ERK1/2 (p-ERK1/2) in tumor cells was investigated using immunohistochemistry. Results: FOXC1 was variably expressed in C-X-C motif chemokine 12-associated reticular stromal cells, histiocytes, (myo)fibroblasts, and endothelial cells. The phenotypes of cases were categorized as dormant (high p-p38/low p-ERK1/2; n=30, 25.0%), active (high p-ERK1/2/low p-p38; n=25, 20.8%), or intermediate (others; n=65, 54.2%). Lower FOXC1+ stromal cell infiltration was associated with the dormant phenotype, the precursor T lymphoblastic leukemia/lymphoma subtype, and inferior overall survival rates, whereas higher FOXC1+ stromal cell infiltration was associated with the active phenotype and favorable patient prognosis (p < 0.05 for all). Conclusion: These results suggested that FOXC1+ stromal cells within the microenvironments of T and NK cell lymphomas might be related to tumor phenotypes.
DOI
10.4143/crt.2020.032
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Nahm, Ji Hae(남지해) ORCID logo https://orcid.org/0000-0003-0902-866X
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
Yoon, Sun Och(윤선옥) ORCID logo https://orcid.org/0000-0002-5115-1402
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180337
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