Proffered Papers— Basic Science/Biology

CYTOKINE LEVELS IN SERUM OF THE PATIENTS WITH SOFT TISSUE SARCOMAS AND THEIR RELATIONSHIP TO ALTERATIONS OF ROUTINE BLOOD TESTS

P.Rutkowskil, J. Kaminska ₂, A. Rysinska ₂, j. Steffen₃, W. Ruka’ ₁ Soft Tissue/Bone Sarcomas Department; ₂ Tumor Markers Department , ₃ Department of Immunology MSklodowska-Curie Memorial Cancer Center-Institute; Warsaw, Roentgena 5; Poland

Introduction: It has been demonstrated that several cytokines may be synthesised and released by many lymphoid and epithelial malignant tumors and that raised serum level of various cytokine may affect the prognosis. It has been also reported that cytokine levels may influence some changes in the blood tests, which was also found as negative prognostic factors in patients with malignancy. There are only a few reports about cytokine production in such rare group of malignant solid tumors as soft-tissue sarcomas. The aim of the study was to evaluate the profile of the selected cytokines in serum of untreated patients with malignant soft-tissue tumors. Then we attempted to correlate these results with the pretreatment routine blood tests (RBC, haemoglobin level HGB , WBC, platelets count PLT, white blood differential count - neutrocyte count NE, lymphocyte count LY, monocyte count MO).

Materials and Methods: 144 patients (74 males, 70 female; mean age 50.1 ± 16..9 yr.) with histologically proven soft-tissue sarcomas before treatment were enrolled into the study. In the study we evaluated serum level of 13 types of cytokines and their soluble receptors (IL-IRA, Il-2SR, IL-6, IL-8, IL-10, EL-6SR, TNFRI, TNFRII, TNFA, GCSF, MCSF, bFGF, VEGF) with ELISA method. Peripheral blood samples from 45 healthy volunteers were collected as controls. Statistical analysis was performed using Kolmogorov-Smirnov and Mann-Whitney U tests (p<0.05).

Results: A significant differences in 11/13 cytokines production (IL-IRA, 11-2SR, IL-6, IL-8, IL-10, TNFRI, TNFRII, TNFA, MCSF, bFGF, VEGF) [p<0.001] were observed between malignant soft tissue tumors and healthy subjects group. Elevated serum level of complex of several cytokines (particularly: IL-IRA, Il-2SR, IL-6, IL-8, EL-10, MCSF, TNFRI) correlated significantly (p<0.001) with the most frequently founded alterations in the blood tests: neutrophilia (29.5% of cases), decreased HGB (22.3%), monocytosis (22.3%) and thrombocytosis (14.5%). In 10% of patients we found lymphocytopenia (LY<1,0), which demonstrated the relationship to serum levels of IL-6, IL2SR, MCSF. Additionally it was detected that increased sera several cytokin levels and also blood test abnormalities correlated significantly with more advanced stage of the primary tumor (size and grade).

Conclusions: The results of this study suggest that cytokine production is probably involved in soft tissue sarcomas progression, what is implied by their increased sera levels in soft-tissue sarcomas versus controls. The results of the analysis may also suggest that important biological effects and immunological implications of the particular cytokins can reflect in routine blood tests abnormalities. Sera levels of selected cytokines may be useful matker in the diagnosis of soft tissue sarcomas.