Forkhead box C1 (FOXC1) expression in stromal cells within the microenvironment of T and NK Cell lymphomas: Association with tumor dormancy and activation

Ji Hae Nahm, Woo Ick Yang, Sun Och Yoon

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1273-1282
Number of pages10
JournalCancer Research and Treatment
Volume52
Issue number4
DOIs
Publication statusPublished - 2020 Oct

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT) (No. NRF-2019R1A2C1002370).

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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