Determination of Interleukin-4, -5, -6, -8 and -13 in Serum of Patients with Breast Cancer Before Treatment and its Correlation to Circulating Tumor Cells.
OBJECTIVE
Circulating tumor cells (CTCs) in women with breast cancer are an indication of prognosis before starting systemic treatment. The aim of this study was the evaluation of cytokine profiles as marker for CTC involvement.


METHODS
The analysis of CTCs, the time of blood sampling and the methodology were prospectively designed. There were two groups of patients: 100 women with a positive result for presence of CTCs and 100 women negative for CTCs. These groups were matched into pairs by tumor factors and survival/death. A multi-array ELISA was used to screen T-helper cell (Th) 2 cytokines. The results were analyzed by Spearman correlation coefficient and Mann-Whitney U-test.


RESULTS
In patients who were CTC-negative, expression of interleukin-8 (IL-8) and IL-13 was increased (p=0.017 and p=0.045, respectively) if they were negative for progesterone receptor. In patients who died from their tumor, correlation between hormone receptor negativity and an increase in IL-4 was found. IL-5 was increased in patients with lymph node-positive and human epidermal growth factor receptor 2 (HER2)-positive disease (p=0.042). Moreover IL-4 was increased in patients with progesterone receptor-positive and estrogen receptor-negative status (p=0.024). Furthermore, the level of IL-6 was increased in patients with tumor grade G3 without progesterone receptor expression.


CONCLUSIONS
Th2 cytokines are significantly modified in patients who are CTC-negative and progesterone receptor-positive. We suppose that an increase of IL-4 depends on hormone receptor status. In literature, a correlation between IL-4 and resistance to apoptosis is described. We suspect that IL-4 is responsible for the poor outcome of these cases.
Department of Gynecology and Obstetrics, Ludwig Maximilians University, Munich, Germany.
Alexander
A
König
Department of Gynecology and Obstetrics, Ludwig Maximilians University, Munich, Germany.
Theresa
T
Vilsmaier
Department of Gynecology and Obstetrics, Ludwig Maximilians University, Munich, Germany.
Brigitte
B
Rack
Department of Gynecology and Obstetrics, Ludwig Maximilians University, Munich, Germany.
Klaus
K
Friese
Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
Wolfgang
W
Janni
Department of Gynecology and Obstetrics, Ludwig Maximilians University, Munich, Germany udo.jeschke@med.uni-muenchen.de.
Udo
U
Jeschke
Department of Gynecology and Obstetrics, Ludwig Maximilians University, Munich, Germany.
Ulrich
U
Andergassen
Department of Gynecology and Obstetrics, Ludwig Maximilians University, Munich, Germany.
Elisabeth
E
Trapp
Department of Gynecology and Obstetrics, Ludwig Maximilians University, Munich, Germany.
Julia
J
Jückstock
Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
Bernadette
B
Jäger
Department of Gynecology and Obstetrics, Ludwig Maximilians University, Munich, Germany.
Marianna
M
Alunni-Fabbroni
Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
Thomas
T
Friedl
Department of Gynecology and Obstetrics, Ludwig Maximilians University, Munich, Germany.
Tobias
T
Weissenbacher
D001943:Breast Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007378:Interleukins / Q000097:blood*; D008207:Lymphatic Metastasis; D060787:Neoplasm Grading; D009360:Neoplastic Cells, Circulating
C508606:CXCL8 protein, human; C508598:IL4 protein, human; C508599:IL5 protein, human; C508600:IL6 protein, human; D018793:Interleukin-13; D015848:Interleukin-5; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D015847:Interleukin-4
Breast cancer; IL-13; IL-4; IL-5; IL-6; IL-8; circulating tumor cells