Discriminant analysis involving serum cytokine levels and prediction of the response to therapy of patients with Hodgkin lymphoma.

Current standard diagnostic methods do not identify patients with Hodgkin lymphoma (HL), who are at high risk of failure after the first-line treatment. In HL patients, serum cytokine levels are frequently elevated and correlate with clinical and pathological features of the disease as well as with disease-free survival and overall survival. The aim of this study was to investigate if pretreatment serum cytokine and cytokine receptor concentrations evaluated by discriminant analysis could be predictive of response to standard first-line treatment in HL. The study involved 48 previously untreated patients with histologically confirmed classical HL and no EBV infection. Treatment included chemotherapy and involved field radiotherapy or radiotherapy alone. At the end of treatment, 71 % of patients reached complete response (CR), and 29 %, in partial response. To identify parameters predictive of nonachievement of CR after the first-line treatment, the discriminant analysis was used. The following variables were included in the analysis: clinical stage, sex, age, histologic subtype, bulky mediastinal mass, systemic symptoms and the number of involved nodal areas, lactate dehydrogenase (LDH) activity, and serum levels of 12 cytokines/cytokine receptors. The resulting classifying function assigned a discriminant power to the following variables: the levels of vascular endothelial growth factor, interleukin-8, macrophage colony stimulating factor, basic fibroblast growth factor, soluble tumor necrosis factor receptor I, and LDH activity. The accuracy of predicting CR and non-CR was 94 and 43 %, respectively.

[The prognostic role of clinical factors, VEGF, IL-8 and sTNF-R1 in cutaneous melanomas at locoregional stage]. / Znaczenie prognostyczne czynników klinicznych oraz oznaczania stezenia VEGF, IL-8 i sTNF-R1 w czerniakach skóry o zaawansowaniu lokoregionalnym.

UNLABELLED: The treatment results of patients with locoregional melanoma are still not satisfactory - up to 50% of patients experience recurrence and (or) disease dissemination. The aim of the study was to assess the prognostic value of clinical factors and serum cytokines of patients with cutaneous melanoma in locoregional stage. MATERIAL AND METHODS: 149 patients at stage I-III according AJCC treated between 2007-2010 were included. Pre-surgery serum levels of VEGF IL-8 and sTNF-R1 were analyzed by ELISA method in 74 melanoma patients and 50 healthy controls. The median follow-up time was 16 months (range: 1-81 months). RESULTS: The most important factors influencing the disease-free survival (DFS) are: staging system according to AJCC) (p < 0.001), regional nodal stage (pN) (p < 0.001), primary tumor (Breslow) thickness (pT) (p = 0.013) and melanoma ulceration (p = 0.004). The serum levels of selected cytokines were significantly higher in melanoma patients than in healthy volunteers (VEGF, p < 0.001; sTNF-R1, p < 0.001; IL-8, p = 0.001). There were no significant relationships between level of cytokine, recurrence or clinical/pathological parameters. CONCLUSIONS: The AJCC staging system gives the most accurate insight into prognosis of melanoma patients at locoregional stage after primary therapy. Cytokine serum profile in melanoma patients at locoregional stage has limited value for predicting tumor burden and treatment outcomes.

Serum macrophage colony-stimulating factor (M-CSF) in patients with Hodgkin lymphoma.

Macrophage colony-stimulating factor (M-CSF) was recently implicated by in vitro studies as a survival and proliferation factor for Hodgkin/Reed-Sternberg cells. We evaluated pre-treatment serum M-CSF levels in 66 patients with histopathologic diagnosis of classical Hodgkin lymphoma (HL) and looked for possible correlations with baseline clinical characteristics. Significantly higher M-CSF serum concentrations were found in patients with bulky mediastinal mass, systemic symptoms, and elevated ESR but not LDH. There was no significant association between M-CSF level and sex, clinical stage, number of lymph node areas involved, and histopathological subtype of HL. We conclude that serum M-CSF levels are frequently elevated in HL patients and are significantly related to the presence of bulky mediastinal mass and systemic symptoms. These observations may indicate a pathogenetic role of M-CSF in Hodgkin lymphoma.

A survey of prognostic value of serum factors in multiple myeloma patients before treatment: macrophage-colony stimulating factor (M-CSF) is a powerful predictor of survival.

Cytokines are involved in the pathogenesis of multiple myeloma (MM) and other cancers. The aim of this study was to evaluate a range of cytokines of diverse activity in patients with multiple myeloma for a possible prognostic value. Concentrations of the following cytokines and cytokine receptors were measured by ELISA in the sera of 64 untreated MM patients: IL-6, IL-8, IL-10, TNFα, sTNF R I and II, sIL-2Rα, IL-1ra, M-CSF, G-CSF, VEGF, and bFGF. Serum levels of sTNF RI, IL-6, and bFGF were elevated in over 50% of patients. There was an inverse relationship between sTNF RII, TNFα, IL-1ra, and albumin levels. There was no significant relationship between cytokines/cytokine receptors and other serum correlates of myeloma. In a univariate survival analysis, ß2-microglobulin, LDH, sIL-2Rα, sTNF RI, and M-CSF were significant variables. In a multivariate analysis, only M-CSF and ß2-microglobulin retained a significant influence on survival. Serum M-CSF may be considered another independent and clinically useful prognostic factor in multiple myeloma.

Clinical significance of serum CA-125 and soluble tumor necrosis factor receptor type I in cervical adenocarcinoma patients.

HYPOTHESIS: The purpose of this study was to answer the question whether the measurement of the pretreatment tumor markers and cytokine levels would be of clinical use in patients with cervical adenocarcinoma. METHODS: CA-125, carcinoembryonic antigen (CEA), and squamous cell carcinoma (SCC), as well as interleukin 6 (IL-6), IL-8, vascular endothelial growth factor, IL-1 receptor antagonist, soluble tumor necrosis factor receptor type I (sTNF RI), and sTNF RII, were assessed in the sera of 120 cervical adenocarcinoma patients. RESULTS: CA-125 presented a better diagnostic sensitivity than did CEA and SCC, whereas the concentration of most cytokines, except for sTNF RII, revealed higher sensitivity, than did the standard tumor markers. The highest sensitivity was found for sTNF RI. The concentrations of the examined parameters were found to be significantly higher in patients with advanced stage (IIB-IV) as compared with patients with I-IIA stage. [Float1]Serum concentration of IL-6 was the only one that differs significantly, depending on the histological grade. During the 3-year follow-up, 25 patients relapsed, and 73 patients were disease-free. Significantly higher pretreatment serum concentrations of the examined parameters (except for SCC and IL-1 receptor antagonist) were found in patients who developed recurrences. Soluble tumor necrosis factor receptor type I and CA-125 were found to present the highest sensitivity, with areas under the receiver operating characteristic curve of 0.833 and 0.809, respectively. As the result of univariate analysis, CA-125, CEA, sTNF RII, IL-6, sTNF RI, and clinical stage were considered factors of poor prognosis. Multivariate analysis has proven that CA-125 and clinical stage were the only significant independent prognostic factors of the disease-free survival. CONCLUSION: CA-125 is an independent prognostic factor for disease-free survival. Our results have also demonstrated that sTNF RI is probably the most useful marker in cervical adenocarcinoma patients, especially in the early stages of disease.

Squamous cell carcinoma antigen 1 and 2 expression in cultured normal peripheral blood mononuclear cells and in vulvar squamous cell carcinoma.

Squamous cell carcinoma antigen (SCCA) is expressed in normal squamous cell epithelia and in squamous cell carcinomas (SCC). Two nearly identical genes encode the inhibitory serpins SCCA1 (SERPINB3) and SCCA2 (SERPINB4). Serum levels of SCCA are elevated in patients with benign skin diseases and in patients with SCC. SCCA, used for the monitoring of SCC patients, presents no satisfactory diagnostic specificity. As we have shown previously, the reverse transcription polymerase chain reaction (RT-PCR)-based SCCA messenger RNA (mRNA) testing aimed at detecting disseminated cancer cells may be hampered by the false-positive results due to SCCA expression in activated peripheral blood mononuclear cells (PBMC). The aim of this study was to assess the expression of SCCA at mRNA and protein levels in cultured normal PBMC, compared to that in vulvar SCC (VSCC) samples. High SCCA concentrations were found in vulvar tumours and in metastatic lymph nodes, while negative inguinal lymph nodes from the same patients often presented significantly less SCCA. In normal activated PBMC, the level of SCCA protein was the lowest. At the mRNA level SCCA was detectable in normal PBMC even in cultures with no mitogen stimulation, but only by the nested RT-PCR, contrary to VSCC samples found to be SCCA positive already in one-step PCR. Both SCCA1 and SCCA2 transcripts were present in cultured PBMC; SCCA1 was expressed at a higher level than SCCA2. In conclusion, both SCCA forms are detectable in normal PBMC cultured in vitro. SCCA expression level in normal PBMC is much lower than in the squamous epithelium-derived cells. In VSCC, in addition to tumour itself, metastatic lymph nodes seem also to be a potential source of serum SCCA.

Serum soluble tumour necrosis factor receptor type I concentrations independently predict prognosis in patients with breast cancer.

BACKGROUND: The aim of this study was to exploit the potential clinical use of circulating cytokine assessment in patients with breast cancer. METHODS: The following circulating cytokines were measured in 210 histopathologically confirmed, untreated breast cancer patients: interleukin 6 (IL-6), tumour necrosis factor-α (TNFα), interleukin 8 (IL-8), soluble tumour necrosis factor receptor type I (sTNF RI), sTNF RII, interleukin 1 receptor antagonist (IL-1ra), interleukin 10 (IL-10), macrophage colony-stimulating factor, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). The patients have been followed-up for 10 years. RESULTS: bFGF and VEGF showed the highest diagnostic sensitivity. Only IL-6 concentrations were related to the clinical stage. A high percentage of patients in clinical stage I showed increased serum sTNF RII, VEGF and bFGF concentrations, of which only sTNF RII was found to be increased in a smaller percentage of patients with more advanced disease compared with patients with early stage disease. Patients aged 50 years and more presented with significantly higher concentrations of sTNF RI, IL-10, IL-6 and VEGF compared with younger patients. In multivariate analysis, a significant value of pretreatment serum sTNF RI concentrations, next to stage and oestrogen receptors status, was its utility as an independent prognostic factor of the overall survival in patients with breast cancer. CONCLUSIONS: Serum sTNF RI may be considered an additional, independent and clinically useful factor of poor prognosis in patients with breast cancer.

Procollagen I amino-terminal propeptide as a potential marker for multiple myeloma.

OBJECTIVES: Investigating relationship between bone markers, cytokines and conventional prognostic parameters in patients with multiple myeloma (MM) and to assess the clinical application of bone turnover markers. DESIGN AND METHODS: Sixty-four patients with MM were examined before treatment and followed for survival for over 7 years. Serum concentrations of bone markers and cytokines were determined by the Roche and R&D kits, respectively. Standard deviation scores (SDS) were employed to normalize values. RESULTS: Collagen fragments (beta-CTX) were elevated in 47%, procollagen I amino-terminal propeptide (PINP)-in 28%, and osteocalcin (OC) in 11% of patients. The values of the SDS of PINP and OC, but not beta-CTX significantly decreased with MM stage. beta-CTX inversely correlated with vascular endothelial growth factor (VEGF) and albumin, and directly correlated with serum macrophage colony-stimulating factor (M-CSF). OC values correlated with albumin and beta2-microglobulin. PINP inversely correlated with LDH. The SDS values of PINP were significantly lower in MM patients with advanced bone disease. CONCLUSIONS: Circulating PINP concentration may be a useful marker for monitoring of treatment of multiple myeloma patients with bone lytic lesions, in particular, of patients treated with preoteasome inhibitors.

Cytokines as potential tumour markers.

BACKGROUND: Cytokines and cytokine receptors contribute importantly to each step of cancer development and progression, and deregulated levels of cytokines and cytokine receptors can be detected in cancer patients locally and systemically. OBJECTIVE: This review aims to outline and discuss the current status of cytokines and their receptors as potential diagnostic, prognostic, predictive and risk indicators, exemplified in cervical, ovarian, breast, prostate, colorectal, gastric, and non-small cell lung cancers and in sarcomas. METHODS: The Medline database was searched for articles on the relevant cancers, published in the English language, using combinations of the following keywords: cytokine, interleukin, growth factor, diagnostic, prognostic, predictive, serum, ascitic and expression. The searches yielded over 2000 papers, and an arbitrary selection of the cited literature was made to present the developments in the field. RESULTS/CONCLUSION: Cytokines, unspecific by definition, present certain patterns of deregulation, often related to clinical characteristics of cancer patients. Some cytokines, most often VEGF, IL-6 and EGFR, present a value of independent prognostic indicators. So far, only local EGFR and HER2 expression assessment in a few cancer types has been accepted for routine use, to qualify patients for a targeted therapy. The authors believe that cytokines may contribute importantly to cancer management in the future; to more likely to indicate prognosis, to identify patients who might benefit from a particular treatment, to monitor treatment response and disease recurrence, and, finally, possibly as part of a larger panel of tumour markers, to improve diagnosis.

The quality of life and hormonal disturbances in testicular cancer survivors in Cisplatin era.

OBJECTIVES: To assess the degree of hormonal abnormalities in testicular cancer survivors and the effect of these changes on patients' quality of life. METHODS: Men with complete remission of testicular cancer for over 2 yr were eligible. Patients completed the State-Trait Anxiety Inventory (STAI), the Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI), the International Index of Erectile Function (IIEF), and the Sexual Functioning Questionnaire (SFQ), and rated their physical and psychological well-being, quality of life, and relationship with their partner. Levels of the hormones testosterone, estradiol, thyreotropin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin were determined. Relationships between hormone levels and questionnaire results were assessed. RESULTS: A total of 326 men were tested, of whom 269 were treated with platinum-based chemotherapy. The most common endocrine abnormalities were above-normal gonadotropin levels (LH, 55%, and FSH, 49% of cases) and lowered testosterone (15%). Twenty-seven percent (STAI) and 28% (HADS) of the patients had abnormal anxiety levels, while the depression rate was 15% (BDI) and 18% (HADS); 40% of patients had erectile dysfunction. Linear regression analysis excluding the influence of age showed higher depression levels in the BDI among patients with elevated LH (p=0.010) or FSH (p=0.017). Patients with above-normal LH showed increased sexual problems in the SFQ (p=0.030). Elevated gonadotropins correlated with deteriorated physical well-being (p=0.028). Men with abnormal estradiol were more prone to erectile dysfunction (p=0.009). CONCLUSIONS: Hormonal abnormalities have a negative impact on the quality of life of testicular cancer survivors.

Serum cytokine levels and the expression of estrogen and progesterone receptors in breast cancer patients.

BACKGROUND: The aim of this study was to assess the correlation between serum concentrations of cytokines and soluble cytokine receptors in breast cancer patients and the expression of estrogen and progesterone receptors in tumor cells. METHODS: The study comprised 158 female breast cancer patients before treatment and 50 healthy individuals as a reference group. RESULTS: The study revealed significantly higher concentrations of most cytokines in breast cancer patients compared to the reference group. Assessment of the correlation between cytokine concentrations in serum and the expression of estrogen and progesterone receptors in tumor cells showed significantly higher interleukin-8 (IL-8) concentrations in patients lacking progesterone receptors in comparison to patients with these receptors. The concentrations of cytokines and their soluble receptors as a function of the expression of estrogen and progesterone receptors were also analyzed in two age groups. In younger patients, aged 50 years and below, no significant differences were found between serum cytokine concentrations and the expression of both estrogen and progesterone receptors. In patients older than 50 years, significantly higher IL-8 concentrations were observed in individuals lacking progesterone receptors, whereas IL-1ra was significantly higher in those lacking estrogen receptors. CONCLUSIONS: IL-1ra and IL-8 concentrations in serum, together with a lack of estrogen and progesterone receptors in tumor cells, in breast cancer patients older than 50 years could represent additional predictive factors for this disease.

Pretreatment serum levels of cytokines and cytokine receptors in patients with non-small cell lung cancer, and correlations with clinicopathological features and prognosis. M-CSF - an independent prognostic factor.

OBJECTIVES: Cytokines are potential new serum markers, especially desirable for malignancies with poor prognosis like non-small cell lung cancer (NSCLC). METHODS: Cytokines, tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6 and IL-8, soluble TNF (sTNF) RI, sTNF RII, soluble IL-2 receptor-alpha, IL-1 receptor antagonist (IL-1ra), IL-10, vascular endothelial growth factor, basic fibroblast growth factor, and macrophage (M-CSF) and granulocyte colony-stimulating factor, as well as tumor markers - carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and CYFRA 21.1 - were assessed in the sera of 103 untreated NSCLC patients, and these cytokines and tumor markers were referred to clinical parameters of the disease and to the overall survival of patients evaluated during a 6-year follow-up. RESULTS: Most of the factors analyzed were found to be elevated in the sera of NSCLC patients, and increases in IL-6, IL-8 and sTNF RI were noted in the greatest proportion of stage I patients. Most cytokine/cytokine receptor levels revealed higher sensitivity than the standard tumor markers; IL-6 and IL-1ra levels were significantly different in patients with squamous cell versus adenocarcinoma; IL-6 and IL-10 were related to the tumor size, while IL-6 and M-CSF levels significantly increased with disease progression. A significant prognostic value of pretreatment serum M-CSF and CEA levels in NSCLC patients has been shown, but only M-CSF proved to be an independent prognostic factor. CONCLUSIONS: Increased pretreatment serum M-CSF level is a significant independent predictor of poor survival in patients with NSCLC.

Sera of lung cancer patients affect the release of Th1, Th2 and monocyte-derived cytokines, and the expression of IL-2Ralpha by normal, stimulated mononuclear cells.

We have shown that the sera of lung cancer patients affect the response of ConA-stimulated normal peripheral blood mononuclear cells by decreasing the expression of IL-2Ralpha and inhibiting the release of IL-1beta and IL-2. A tendency to enhance the release of IL-6 was also observed. We conclude that an imbalance in the Th1/Th2 cytokine response, typical for cancer patients, may at least partly be related to soluble factors circulating in the patients' blood. We discuss a putative role of serum IL-10, IL-1ra, and soluble IL-2Ralpha in the effects observed.

Cytokine and cytokine receptor serum levels in adult bone sarcoma patients: correlations with local tumor extent and prognosis.

BACKGROUND AND OBJECTIVES: We analyzed the correlations between pretreatment serum levels of 11 cytokines and soluble cytokine receptors (interleukin 6 (IL-6); interleukin 8 (IL-8); interleukin 10 (IL-10); vascular endothelial growth factor (VEGF); basic fibroblast growth factor (bFGF); macrophage colony-stimulating factor (M-CSF); granulocyte colony-stimulating factor (G-CSF); interleukin 1 receptor antagonist (IL-1ra); sIL-2Ralpha; tumor necrosis factor receptor I (TNF RI), and TNF RII) with clinico-pathological features and survival of patients with bone sarcomas. METHODS: Altogether, 72 patients with bone sarcomas without distant metastases before treatment (26 osteosarcomas-36%, 23 chondrosarcomas-32%, 13 Ewing's sarcomas/PNET-18%, 10 giant-cell tumors-14%), 22 patients with benign non-inflammatory bone tumors and 50 age-matched healthy controls were included into this prospective study. RESULTS: Median serum levels of 9/11 cytokines, with the exception of sIL-2Ralpha and G-CSF, were significantly higher in sarcoma patients than in controls. Median serum levels of IL-6, IL-8, IL-1ra, TNF RI, and M-CSF were significantly higher in patients with bone sarcoma as compared to patients with benign bone tumors. In 45.9% of sarcoma patients, six or more cytokines and cytokine receptors, including those that are involved in bone destruction (e.g., IL-6 and IL-8) and bone formation (e.g., IL-1ra and TNFRI and TNFRII), were elevated in parallel. Serum levels of IL-6, IL-8, TNF RI, TNF RII, and VEGF correlated significantly with tumor size (<10 cm vs. >or=10 cm in diameter) and serum levels of IL-6, IL-8, TNF RI, and IL-1ra correlated significantly with local tumor extent (E2/4 vs. E5/6 according to the classification proposed by Spanier et al. 46). Moreover, serum levels of IL-1ra and IL-6 were significantly higher in patients with small tumors (<5 cm in diameter) infiltrating structures adjacent to the periosteum (E5/6) than in large tumors (>10 cm in diameter) but confined to the bone and periosteum (E < 4). The lowest median serum levels of 8/11 cytokines/cytokine receptors were found in patients with giant-cell tumors. In an univariate analysis, increased serum levels of IL-1ra, IL-6, IL-8, IL-10, sIL-2Ralpha, M-CSF, TNF RI, and TNF RII, the number of cytokines elevated, higher tumor grade, larger tumor size, greater local extent (E) and patients' age >35 years correlated with poor overall survival (OS) (P < 0.05). Similarly, high serum levels of IL-1ra, IL-6, TNF RI and TNF RII, tumor grade, tumor size, and tumor local extent (E) (P < 0.05) affected disease free survival (DFS) in univariate analysis. Multivariate analysis using Cox's proportional hazards model showed that high serum levels of IL-1ra (P = 0.039) and TNF RI (P = 0.048), the number of serum cytokines above normal cut-off values (0-1 vs. 2-5 vs. >or=6; P = 0.029), greater tumor local extent E (E2/4 vs. E5/6; P = 0.02) correlated significantly with shorter OS. Only E was found as an independent prognostic factor for DFS (P = 0.04). CONCLUSIONS: These findings indicate that cytokines and soluble cytokine receptors, both physiologically involved in bone destruction and bone formation, have an essential role in the progression of malignant bone tumors.

Cytokine serum levels in soft tissue sarcoma patients: correlations with clinico-pathological features and prognosis.

We investigated the correlations between serum levels of selected proinflammatory, hematopoietic and angiogenic cytokines and soluble cytokine receptors with the clinico-pathological features and prognosis in soft tissue sarcoma patients. Serum levels of 9 cytokines (TNFalpha, IL-1ra, IL-6, IL-8, IL-10, M-CSF, G-CSF, VEGF, bFGF) and 4 free cytokine receptors (sIL-2R alpha, sIL-6R, TNFRI, TNFRII) were measured by means of an enzyme-linked immunoadsorbent assay kit in 156 soft tissue sarcoma patients before the treatment and in 50 healthy controls. Serum levels of 10 cytokines and cytokine receptors were also assayed during patients' follow-up after the treatment. Significantly elevated pretreatment serum levels of 11/13 cytokines and cytokine receptors were found in sarcoma patients, as compared to healthy controls. In 40.4% of patients 6 or more cytokines and cytokine receptors (most frequently: TNF RI, IL-6, IL-8) were elevated in parallel. Serum levels of IL-6, sIL-2R, VEGF, M-CSF and TNF RI correlated significantly with tumor size and serum levels of IL-8 and IL-6 were significantly higher in patients with Grade 2/3 vs. Grade 1 tumors. We did not observe any significant differences in cytokine serum levels between patients with primary and recurrent tumors and patients with and without distant metastases. Using univariate analysis, overall survival (OS) in all patients was affected by tumor size (<5 cm vs. 5-10 cm vs. >10 cm), tumor grade (G1 vs. G2/3), presence of metastases, pretreatment serum levels of 8 cytokines (IL-6, IL-8, IL-10, sIL-2R, TNF RI, TNF RII, M-CSF, VEGF) and the number of cytokines increased (0-1 vs. 2-5 vs. < or = 6). Elevated serum levels of IL-6, IL-8, IL-10 and sIL-2R alpha, high tumor grade and larger tumor size strongly correlated with shorter disease-free survival (DFS). Multivariate analysis identified G2/3 tumor grade (p = 0.001), the presence of metastases (p = 0.004), elevated IL-6 serum level (p = 0.02), elevated IL-8 serum level (p = 0.048) and the number of cytokine serum levels above upper cut-off values (p = 0.01) as the independent prognostic factors related to OS, and G2/3 tumor grade (p = 0.005) and increased IL-6 serum level (p = 0.035) as independent prognostic factors related to DFS. In a group of patients without metastases (M0) higher tumor grade, elevated serum level of IL-6 and TNF RII, and the number of elevated cytokine serum levels correlated independently with poor survival. We found a significant decrease of several cytokine serum levels in patients after treatment (IL-1ra, IL-6, IL-8, IL-10, TNF RII, M-CSF) [p < 0.05]. Persistently elevated serum level of IL-6 after the treatment has also shown negative prognostic significance for OS (univariate analysis). Serum levels of some proinflammatory, hematopoietic and angiogenic cytokines and cytokine receptors are elevated, frequently in parallel, in a large percentage of soft tissue sarcoma patients. Significant correlations of serum cytokine levels with tumor size and grade suggest that some of these cytokines may be directly or indirectly involved in the progression of soft tissue sarcomas. Serum assays of IL-6, IL-8 and TNF RII before or after the treatment may be useful in establishing soft tissue sarcoma patients prognosis.