FOXP3 Expression Is Related to High Ki-67 Index and Poor Prognosis in Lymph Node-Positive Breast Cancer Patients

Kim, Min Hwan; Koo, Ja Seung; Lee, Soo Hyun

doi:10.1159/000351473

Cited by 17 publications

(15 citation statements)

References 40 publications

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“…These authors attributed the correlation with worse prognosis to Treg infiltration. Other study using immunohistochemistry technique also showed association of FOXP3 expression by tumor cells with higher histological grade [48]. However, in this study, all tumor samples showed cytoplasmic or both cytoplasmic and nuclear FOXP3 expression, suggesting frequent deregulation of FOXP3 localization and failure to translocate to the nucleus in breast cancer cells and explaining the correlation with worse prognosis.…”

Section: Discussioncontrasting

confidence: 54%

FOXP3Allelic Variants and Haplotype Structures Are Associated with Aggressive Breast Cancer Subtypes

et al. 2017

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FOXP3 genetic polymorphisms have been associated with cancer development and prognosis. In this context, the present study aimed to evaluate the g.10403A>G (rs2232365) polymorphisms and g.8048A>C (rs3761548), in aggressive breast cancer (BC) subtypes, including, Luminal B HER2+ (LB), HER2-enriched (HER2+), and triple-negative (TN). Polymerase chain reaction followed by enzymatic restriction was performed to genotyping 117 BC samples and 300 controls. A significant association of AA genotype (g.10403A>G) in relation to BC susceptibility (OR = 1.93; 95% CI = 1.01–3.66; p = 0.046) was observed. The GG (g.10403A>G) genotype was correlated with higher proliferation index (Ki-67) in HER2+ subtype (τ = 0.47; p = 0.019) and advanced TNM staging in TN (τ = 0.23; p = 0.032). A correlation of AA genotype (g.8048A>C) with higher Ki-67 (τ = −0.47; p = 0.018) and lower histological grade (τ = 0.39; p = 0.026) in HER2+ was also found. GA haplotype was correlated with lower histological grade (τ = −0.15; p = 0.009) and higher Ki-67 (τ = 0.43; p = 0.036) in HER2+ and advanced staging in TN (τ = 0.29; p = 0.044). On the other hand, AC haplotype was correlated with lower Ki-67 (τ = −0.54; p = 0.005) and staging (τ = −0.29; p = 0.027) in HER2+ and TN respectively. Results showed that FOXP3 influence regarding clinical outcome depends greatly on the BC subtype and indicated this transcription factor as a promising marker in aggressive BC subtypes.

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Section: Discussioncontrasting

confidence: 54%

FOXP3Allelic Variants and Haplotype Structures Are Associated with Aggressive Breast Cancer Subtypes

et al. 2017

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“…FOXP3 was also a strong prognostic factor for distant metastasis-free survival, but not for local recurrence incidence risk (Merlo et al, 2009). These results were confirmed by other 2 independent studies (Kim MH et al, 2013;Nair et al, 2013). The frequency of FOXP3 positive cancer cells in primary gastric tumors correlated with the incidence of lymph node metastases (Yoshii et al, 2012;Wang et al, 2010) and the 3-year survival rate, indicating a potential association of FOXP3 expression with poor prognosis.…”

Section: Foxp3 Expression and Prognosis In Human Cancersupporting

confidence: 70%

FOXP3 expression in tumor cells and its role in cancer progression

Uva¹,

Sfondrini²,

Triulzi³

et al. 2015

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Forkhead box P3 (FOXP3), a gene member of the forkhead/winged-helix family of transcription regulators, is implicated in regulating immune system development and function. This gene has been found to be of crucial importance for the generation of CD4 + CD25 + regulatory T cells (Tregs). In addition to its expression in the lymphocyte lineage, studies have recently described FOXP3 expression in normal and cancer cells nonhematopoietic-derived, suggesting that FOXP3 exerts a broader function than that on Tregs. A role for FOXP3 as an onco-suppressor gene in human cancers has been suggested based on in vitro studies showing that FOXP3 is implicated in repressing various oncogenes and enhancing expression of tumorsuppressor genes. However, numerous studies in samples from human cancer patients showed a positive correlation between FOXP3 expression and poor prognosis, especially with metastasis. Further investigations are required to clarify the significance of FOXP3 expression in tumor cells and to identify the mechanisms by which it affects prognosis.

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“…As it has been described that several tumor entities are positive for Foxp3, CTLA-4 or CD39/CD73 [6, 16–18], all of them Treg associated markers, we reasoned whether also GARP, a recently described Treg activation marker involved in tolerance induction[9], is expressed on melanoma cells and would functionally contribute to the inhibitory features mentioned above. We found a significant expression of GARP and Foxp3 on melanoma cell lines SK29-MEL-1 (Figure 2A) and UKRV-Mel-15a, UKRV-Mel-21a, Ma-Mel-59a and Ma-Mel-91a (Suppl.…”

Section: Resultsmentioning

confidence: 99%

A key role of GARP in the immune suppressive tumor microenvironment

Hahn

Neuhoff

Landsberg³

et al. 2016

Oncotarget

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In melanoma patients, one of the main reasons for tumor immune escape and therapy failure is the immunosuppressive tumor microenvironment. Herein, suppressive immune cells and inhibitory factors secreted by the tumor itself play a central role.In the present study we show that the Treg activation marker GARP (glycoprotein A repetitions predominant), known to induce peripheral tolerance in a TGF-β dependent way, is also expressed on human primary melanoma. Interestingly, membrane bound GARP is shed from the surface of both, activated Treg and melanoma cells, and, in its soluble form (sGARP), not only induces peripheral Treg but also a tumor associated (M2) macrophage phenotype. Notably, proliferation of cytotoxic T cells and their effector function is inhibited in the presence of sGARP. GARP expression on Treg and melanoma cells is significantly decreased in the presence of agents such as IFN-α, thus explaining at least in part a novel mechanism of action of this adjuvant therapy.In conclusion, GARP in its soluble and membrane bound form contributes to peripheral tolerance in a multipronged way, potentiates the immunosuppressive tumor microenvironment and thus acts as a negative regulator in melanoma patients. Therefore, it may qualify as a promising target and a new checkpoint for cancer immunotherapy.

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FOXP3 Expression Is Related to High Ki-67 Index and Poor Prognosis in Lymph Node-Positive Breast Cancer Patients

Cited by 17 publications

References 40 publications

FOXP3Allelic Variants and Haplotype Structures Are Associated with Aggressive Breast Cancer Subtypes

FOXP3Allelic Variants and Haplotype Structures Are Associated with Aggressive Breast Cancer Subtypes

FOXP3 expression in tumor cells and its role in cancer progression

A key role of GARP in the immune suppressive tumor microenvironment

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