Clinical Significance of Serum Ykl-40 (Chitinase-3-Like-1 Protein) as a Biomarker in Melanoma: an Analysis of 112 Turkish Patients

Background: Angiogenesis plays an essential role in tumor growth and serum levels of YKL-40 , a strong angiogenic factor that promotes tumor vessel development, has been found to be elevated in various cancers. We here investigated correlation between melanoma parameters and serum YKL-40 levels, to assess potential diagnostic, prognostic and predictive values. Material and Methods: Data for 112 pathologically confirmed cutaneous melanomas of any stage were examined retrospectively. ELISA assays were used to measure serum YKL-40 in plasma samples. Results: The baseline serum YKL-40 levels were significantly higher in patients than healthy controls (174.88 vs 120.10 ng/mL, p<0.001). However, values did not correlate with clinicopathological parameters, (p>0.05), and furthermore there was no apparent prognostic influence on melanoma survival (HR: 1.568; 95% CI, 0.580-3.051; p=0.838). Conclusion: Serum YKL-40 can be useful for diagnosis of melanoma, but reliability in assessing prognosis is questionable. We believe that efforts should be made to understand the interaction between YKL-40 and the tumor environment, and establish whether it might be the target for treatment of malignancies.

Circulating serum levels of angiopoietin-1 and angiopoietin-2 in nasopharynx and larynx carcinoma patients.

We aimed to determine the serum levels of angiogenic factors, namely angiopoietins, in nasopharyngeal and laryngeal carcinoma patients. We also aimed to seek the relation of these molecules with tumor grade and their utility as diagnostic biomarkers. We evaluated angiopoietin 1 and 2 levels innasopharynx and larynx cancer patients before treatment. Angiopoietin 2 levels were significantly elevated in larynx carcinoma patients and tended to be elevated in nasopharynx cancer patients compared with healthy controls. However, angiopoietin 1 levels were similar in cancer patients and controls. Angiopoietin 1 levels were significantly higher in nasopharyngeal cancer patients with advanced stages compared to earlier stages. On the other hand, angiopoietin 2 levels were similar in advanced and earlier stage cancer patients.

EMMPRIN and ADAM12 in prostate cancer: preliminary results of a prospective study.

Extracellular metalloproteinase inducer (EMMPRIN) and a disintegrin and metalloproteinase (ADAM12) play a major role in cancer invasion and metastasis owing to the fact that they are directly related to the cell microenvironment and extracellular matrix (ECM) degradation. The aim of this study was to search for an answer to the question "whether the determination of EMMPRIN and ADAM12 values especially in urine may be helpful for the early diagnosis of prostate cancer without employing invasive methods" and also to check whether they may be useful for the determination of the patients with high metastasis risk. Peripheral blood and urine from 66 prostate cancer patients (40 local, 20 locally advanced, 6 metastatic) and 14 healthy controls were evaluated by enzyme-linked immunosorbent assay (ELISA) method. Serum EMMPRIN and ADAM12 values of the patients were seen to be statistically higher than the serum EMMPRIN and ADAM12 values of the healthy controls (p=0.01 and p=0.001, respectively). The urine ADAM12 levels were significantly higher in patients (p=0.013). No significant relationships were found between urine EMMPRIN values of the patients and the healthy controls (p>0.05). Positive correlation between urine EMMPRIN-urine ADAM12 tests was found in total patients group (r=0.683, p=0.001). Our preliminary results revealed that serum EMMPRIN and ADAM12 values and urine ADAM12 values may be useful markers in prostate cancer therapy. Due to the high correlation between these two tests, we are of the opinion that the use of urine ADAM12 in clinic may be sufficient and favorable together with prostate-specific antigen (PSA) for treatment.

For which cancer types can neuron-specific enolase be clinically helpful in Turkish patients?

BACKGROUND: The aim of the present study was to evaluate the serum neuron-specific enolase (NSE) levels in patients with prostate cancer, Hodgkin lymphoma, lung cancer and peripheral nerve tumors. MATERIALS AND METHODS: NSE levels were determined by ELISA in the sera of 100 prostate cancer, 47 Hodgkin lymphoma, 35 lung cancer and 35 peripheral nerve tumor patients and also in 132 healthy controls. RESULTS: The median levels of serum NSE were elevated in patients with lung cancer (p=0.018) and peripheral nerve tumors (p=0.008). NSE levels in prostate cancer and Hodgkin lymphoma patients were higher than the controls but there was no statistically significant difference (p>0.05). CONCLUSIONS: We conclude that NSE may be applied in routine to gain insight about the clinical statuses of various cancer patients, but more studies are needed to determine the organ specificity.

A high serum level of M65 is associated with tumour aggressiveness and an unfavourable prognosis for epithelial ovarian cancer.

PURPOSE: This study was conducted to determine the clinical significance of serum M30 and M65 in epithelial ovarian cancer (EOC). METHODS: A total of 56 patients with EOC and 56 healthy women were included in the study. All of the patients received platinum-based chemotherapy. Pretreatment levels of M30 and M65 were measured using the quantitative ELISA method. RESULTS: The median M30 and M65 serum levels were significantly elevated in the EOC patients compared with the healthy controls (96.7 vs. 69.5, p = 0.028 and 436.4 versus 166.3, p < 0.001, respectively). The cut-off value of 423.4 U/L for M65 determined with ROC analysis, predicted progression with 75.1 % sensitivity and 65.6 % specificity (AUC = 0.708, p = 0.008). Patients with higher M65 levels had shorter progression-free survival (PFS) (p = 0.021). Both M30 and M65 serum levels were significantly higher for serous-type histology (p = 0.001 and p < 0.001, respectively). Increased M65 serum levels were associated with advanced disease (p = 0.005) and higher grade (p = 0.005). Moreover, M65 levels were higher for chemotherapy-resistant patients (p = 0.04). Multivariate analysis revealed that an elevated serum M65 level was the only significant independent prognostic factor (p = 0.039, HR 3.792). CONCLUSIONS: These results indicated that serum M30 and M65 levels were significantly elevated in patients with EOC compared with healthy women. Particularly, high serum M65 levels were associated with poor prognosis and resistance to platinum-based chemotherapy.

Effects of intraperitoneal bevacizumab administration on colonic anastomosis and early postoperative adhesion formation.

AIM: The purpose of this study is to investigate the effect of intraperitoneal (IP) bevacizumab on colonic anastomosis and evaluate the effects on early postoperative adhesion formation. MATERIALS AND METHODS: A total of 24 mature female Sprague-Dawley rats were used for this study. Rats were randomly assigned to a control group that received saline (n = 8) or to experimental groups (n = 8 each) that received bevacizumab at a dose of 2.5 mg/kg (group 1) or 5 mg/kg (group 2). Animals were killed humanely on the seventh day after operation, and measurements of anastomotic strength and biochemical variables were performed. RESULTS: The mean adhesion grade was 2.63 ± 0.92, and 1 ± 0.93 and 0.75 ± 0.71 for the control and test groups, respectively. Bevacizumab significantly reduced adhesion formation in both low-dose and high-dose IP applications (P < .05). When all groups were compared, it was found that VEGF levels decreased significantly only in the tissue (P = .001), whereas there was no significant difference in the blood and the IP fluid (P = .73 and .08, respectively). We evaluated hydroxyproline levels, anastomosis bursting pressure, and histopathological healing scores. When each of these parameters were examined, there was statistical difference between groups (P = .01, .004, and .01, respectively). It was found that these parameters significantly decreased depending on increasing drug dose. CONCLUSION: IP administration of bevacizumab effectively reduced the formation of adhesions and caused significant impairment of anastomotic wound healing when standard doses were administered (5 mg/kg), but the 2.5-mg/kg dosage did not affect the anastomotic wound healing and also effectively reduced the formation of adhesions.

Clinical and prognostic significance of coagulation assays in advanced epithelial ovarian cancer.

OBJECTIVE: Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological tumors and usually diagnosed at advanced stage. We aimed to identify the clinical and prognostic relevance of coagulation tests and their correlation with serum CA-125 levels in advanced EOC. MATERIALS AND METHODS: A total of 33 advanced-stage (stages III and IV) EOC patients were enrolled in the study. Of these patients, 17 had received neoadjuvant chemotherapy and 16 patients received chemotherapy after optimal debulking surgery. Several clinicopathologic factors, coagulation assays, routine biochemistry tests, and serum CA-125 levels were evaluated before treatment and compared with healthy subjects. RESULTS: All coagulation tests including prothrombin time (PT), activated partial thromboplastin time, international normalized ratio, fibrinogen, D-dimer, and platelet revealed statistically significant difference between patients and control subjects (P ≤ 0.001). Elevated CA-125 levels were correlated with higher D-dimer values (P = 0.03). Prolonged PT was associated with poorer both overall (P = 0.03) and progression-free survival rates (P = 0.04). CONCLUSIONS: Correlation of CA-125 with D-dimer is supposed to reflect hyperactivation of fibrinolytic pathway in the presence of a higher tumor load. Alterations in coagulation pathway reflected by prolonged PT support prognostic effects on survival of advanced-stage EOC patients.

Markers of bone metastases in breast and lung cancers.

AIM AND BACKGROUND: The aim of the present study was to evaluate correlations between serum osteocalcin, osteoprotegerin and NTX (Cross-linked N-telopeptides of Type I Collagen) and urinary NTX in breast and lung cancer patients with bone metastases. These four markers are considered to have important roles in bone formation, resorption and metastases. METHODS: Four markers were determined in the sera of 60 breast cancer and 21 lung cancer patients and healthy controls (n=30). Serum levels were studied using ELISA and EIA. RESULTS: The median levels of serum osteoprotegerin (p<0.001) and osteocalcin (p=0.003) were higher in patients. Significant correlations were observed between the serum NTX-osteocalcin (r=0.431; p<0.001), serum NTX- osteoprotegerin (r=0.42; p=0.003) and serum NTX - urine NTX (r=0.255; p=0.022). CONCLUSION: We conclude that osteocalcin, osteoprotegerin and NTX are independent diagnostic tools. Due to the ease of urine collection, urine NTX may be applied routinely to allow early detection of bone metastases and indicate progression of the disease.

Utility of serum and urine uPAR levels for diagnosis of breast cancer.

Malignant tumors have a capacity to degrade the extracellular matrix by controlled proteolysis. One system involved in these processes is the urokinase-type plasminogen activator (uPA) system. uPAR levels are elevated in tumors from several types of cancer. Our study was planned to investigate serum and urine levels of uPAR in breast cancer patients (n=180) and healthy controls (n=60) by ELISA. Serum (p<0.001) and urine (p<0.001) uPAR values in the patients were both significantly elevated. High serum and urine levels of uPAR can be used as diagnostic tools in lymph node positive patients.

Clinical and prognostic significance of coagulation assays in melanoma.

The activation of coagulation and fibrinolysis is frequently found among cancer patients. Such tumors are considered to be associated with a higher risk of invasion, metastases, and eventually worse outcome. The aim of this study is to explore the clinical and prognostic value of blood coagulation tests for melanoma patients. Pretreatment blood coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), international normalized ratio (INR), D-dimer (DD), fibrinogen (F) levels, and platelet (PLT) counts were carried out. This prospective study included 61 melanoma patients [stage I-II (n=10), stage III (n=14), stage IV (n=37), M1c (n=26) disease], and 50 healthy controls. It included 34 (56%) men, median age 53 years, range 16-88 years. Over half of the patients (54%) were in the metastatic stage and most of them (70%) had M1c. The plasma level of pretreatment blood coagulation tests including DD, F, APTT, INR levels, and PLT counts showed a statistically significant difference between the patient and the control group (P<0.001 for all, but P=0.049 for INR). The levels of INR, DD, F, and PLT counts were higher and APTT was lower in the melanoma group, whereas the PT and PTA levels did not show any significant difference. There was a significant association between PT, PTA, INR, and PLT levels and the age of the patient. Patients with node metastasis in M0 disease had higher levels of PTA and PLT counts (P=0.002 and 0.048, respectively) and lower levels of PT and INR (P=0.056 and 0.046, respectively). The M1c patients tended to have higher plasma F levels (437 vs. 297 mg/dl, P=0.055) than M1a and M1b patients. The 1-year survival rate for all patients was 70%. In association with distant metastasis, advanced metastatic stage (M1c), elevated lactate dehydrogenase, and erythrocyte sedimentation rate, only elevated plasma F levels had a significantly adverse effect on survival among the coagulation parameters (P=0.031). The 1-year survival rates for patients with high and normal F levels were 58 and 88%, respectively. In conclusion, changes in the coagulation-fibrinolytic system are often present in melanoma and elevation in the plasma F level is associated with decreased survival.

Matrix metalloproteinase-9 decreased after chemotherapy in patients with non-small cell lung cancer.

AIMS AND BACKGROUND: The aim of the study was to investigate the alteration in serum matrix metalloproteinase-9 (MMP-9) levels after chemotherapy and the association between the changes in serum levels of MMP-9 and response to chemotherapy in patients with advanced stage non-small cell lung cancer. METHODS AND STUDY DESIGN: Twenty-eight consecutive patients with advanced non-small cell lung cancer and 24 healthy controls were enrolled in the study. The patients were treated with cisplatin-based combination chemotherapy. After two cycles, the response was evaluated. Before and after two cycles of chemotherapy, serum samples were collected from the patients. RESULTS: Prechemotherapy MMP-9 (ng/ml) levels were significantly higher in patients with advanced stage non-small cell lung cancer than in controls (7.2 ± 2.8 vs 4.5 ± 2.1, P <0.001). Prechemotherapy MMP-9 levels were elevated compared to postchemotherapy levels as well (7.2 ± 2.8 vs 5.2 ± 3.3, P = 0.005). Prechemotherapy MMP-9 levels were significantly higher than postchemotherapy MMP-9 levels in patients with partial response (7 patients) (8.2 ± 1.8 and 3.2 ± 2.3, respectively; P = 0.018), but the pre- and postchemotherapy MMP-9 levels were no different in patients with stable disease or progressive disease (21 patients) (7 ± 3.1 and 5.9 ± 3.3, respectively; P = 0.08). CONCLUSIONS: The difference between pre- and postchemotherapy MMP-9 levels in responders was more prominent than that in nonresponders. Whether the decline in serum MMP-9 levels might be used as a marker of response to chemotherapy should be investigated in larger studies.

Lack of diagnostic potential of Dickkopf-1 in colon and rectum cancers.

The Wnt/b-catenin signalling pathway plays crucial roles in development and its aberrant activation is an initial and crucial event in the majority of colon cancers. The Dickkopf-1 (Dkk-1) gene encodes an extracellular Wnt inhibitor that blocks the formation of signalling receptor complexes at the plasma membrane. Here, we report the serum levels of Dkk1 in colorectal cancer patients without any therapy. The levels were determined by enzyme-linked immunosorbent assay (ELISA) in 135 colon and 160 rectum cancer patients, as well as 90 healthy subjects. Data analyses were performed using SPSS software (SPSS 16, Chicago, IL). There were no significant differences among the groups for Dkk-1 (p=0.363). In conclusion, the present study did not confirm that serum Dkk-1 levels could have any diagnostic potential in colon and rectum cancers.

Determination of serum CRP, VEGF, Leptin, CK-MB, CA-15-3 and IL-6 levels for malignancy prediction in adnexal masses.

OBJECTIVE: Investigation of serum markers which could be used in the malignancy prediction of adnexal masses. MATERIAL AND METHODS: Vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), leptin, C-reactive protein (CRP), creatine-kinase-MB (CK-MB) and cancer antigen 15-3 (CA 15-3) levels were determined prospectively in serum samples that were obtained from patients who underwent surgery for an adnexal mass and who were referred to Istanbul University, Faculty of Medicine, Department of Obstetrics and Gynecology, between 2009 and 2011, and then were compared with the serum samples of completely healthy outpatient patients as a control group. Based onto the ovarian cancer status, cases were divided into four groups: 13 patients were included in the early-stage malignant group, 12 patients were included in the advanced-stage malignant group, 25 in the benign group and 19 in the healthy control group. Patients with only epithelial ovarian cancer were included into the cancer group. Ethics Commitee approval was obtained for this study. The budget was supported by the Istanbul University Scientific Research Projects Unit. RESULTS: RESULTS RELATED WITH SENSITIVITY, SPECIFICITY, POSITIVE PREDICTIVE VALUE (PPV), NEGATIVE PREDICTIVE VALUE (NPV) AND ODDS RATIO (OR), RESPECTIVELY, AND THE FOLLOWING VALUES WERE CALCULATED: 48%, 95%, 92%, 59% and +OR 9.6 -OR 0.5 for CA; 15-3; 52%, 75%, 72%, 55%, +OR 2.08 -OR 0.64 for leptin; 72%, 70%, 75%, 66% 2.4-0.5 for IL-6; 24%, 80%, 60%, 45%, 1.2-0.92 for VEGF; 68%, 30%, 55%, 43%, 0.97-1.06 for CRP; and 8%, 70%, 25%, 38%, 026-1.31 for CK-MB. CONCLUSION: CA 15-3, IL-6, Leptin, VEGF and CRP were effective in the prediction of benign and malignant masses; however they may be more suitable in selected cases as they have a limited use because of their inadequate potential regarding sensitivity and specificity.

Serum levels of interleukin-6 and interleukin-10 in Turkish patients with aggressive non-Hodgkin's lymphoma.

There exists strong evidence that tumor growth can be actively controlled by the host immune system and interleukins are known to play a significant role in immune response regulation. Inflammatory cytokines play important roles in the pathogenesis of lymphomas. This study was conducted to investigate the serum levels of IL-6 and IL-10 in patients with aggressive non-Hodgkin's lymphoma (A-NHL) and the relationships with prognostic parameters and therapy. These serum factors were measured in 46 A-NHL patients pathologically verified before and after chemotherapy in comparison with 21 healthy controls using enzyme-linked immunosorbent assays (ELISAs). There were significant differences in the serum IL-10 and IL-6 levels between A-NHL patients and controls (p= 0.038 and p<0.001, respectively). None of the prognostic parameters analyzed was significantly correlated with the serum IL-6 concentrations. This was also true for serum IL-10 values, except for LDH and bone marrow involvement. Serum IL-10 levels were elevated in the group of patients with high level LDH compared with the group of patients with a normal level (p= 0.017). Also, serum IL-10 levels were significantly different in the presence or absence of bone marrow involvement (p= 0.016). In addition, we found a significant relationship between the serum levels of serum levels of IL-6 and IL-10 in patients with A-NHL (r= 0.47, p<0.001). We found that serum IL-10 levels decreased due to chemotherapy effect independent of the chemotherapy response (p= 0.027). However, serum IL-6 levels were not changed. In conclusion, our data suggest that higher serum IL-6 and IL-10 levels can be useful for diagnosis of A-NHL. However, our sample size is small, and larger scale research is needed in this field to provide new knowledge.

Serum levels of angiogenic factors in early breast cancer remain close to normal.

The study which we performed was to determine serum concentrations of angiogenic factors including VEGF, angiogenin and TGF-beta 1 in early stage breast cancer patients. These parameters were measured by ELISA in sera of 90 patients with breast cancer and 75 healthy controls. The mean serum VEGF concentration in patients compared to controls was not significantly different (0.33ng/mL vs 0.43ng/mL, respectively; p=0.156). Likewise, the insignificant change in mean values in patients vs controls was also observed for serum TGF-beta 1 (0.19ng/mL vs 0.19ng/mL, respectively; p=0.215) and serum angiogenin (243.24ng/mL vs 244.5ng/mL, respectively; p=0.976). Statistically significant correlation was found only between the tests, such as VEGF and angiogenin in patients who were included in the study (p<0.001). In conclusion, we couldn't find any diagnostic value between the early stage breast cancer and the three angiogenic parameters.

Statistical interpretation of CA125 and Bcl-2 in serum of patients with late stage ovarian cancer.

OBJECTIVES: The present study was conducted to investigate the sensitivity, specificity, predictive values and accuracy of serum CA125 and Bcl-2 levels and their combination in advanced epithelial ovarian cancer patients. METHODS: Healthy controls (n = 117) with no gynecologic problems and patients with ovarian carcinoma (n = 117), pathologically verified, consecutively admitted to the Istanbul University, Oncology Institute during a one-year period were investigated. Serum Bcl-2 and CA125 were determined by using enzyme linked immunosorbent assay method. RESULTS: The serum bcl-2 and CA125 levels were significantly higher in patients with ovarian cancer than in the control group (P < 0.001). The diagnostic sensitivity and specificity, predictive values and accuracies were calculated for each marker and their combination. CONCLUSION: The best result was achieved with the combination of CA125-bcl-2. This combination fulfills the need of diagnosis of ovarian carcinoma for the best sensitivity and specificity.

The diagnostic value of macrophage migration inhibitory factor (MIF) in gastric cancer.

The present study was conducted to investigate the sensitivity, specificity, predictive values and accuracy of serum MIF, CEA, CA 19-9 levels and their various combinations in patients with gastric cancer. Study group consists of pathologically verified, gastric cancer (n = 63) and apparently healthy controls (n = 50). Serum MIF concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Serum values of patients were significantly higher than the controls (p = 0.011). Diagnostic sensitivity and specificity, predictive values and accuracies were calculated for each marker and their various combinations. The best results were achieved with the marker combination of MIF-CEA-CA 19-9 and MIF-CEA combination. In our opinion, the combination of the markers MIF-CEA is a valuable diagnostic tool for gastric cancer.

Circulating levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-3 (MMP-3), and BCL-2 in malignant melanoma.

Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis that stimulates proliferation, migration, and metastasis of melanoma. In literature, all studies concerning influences of matrix metalloproteinases (MMPs) and antiapoptotic proteins on VEGF-induced angiogenesis in melanoma patients have been performed in tissue scale in melanoma. The objective of this study was to determine the value of circulating serum VEGF and its possible mechanisms of angiogenesis by circulating VEGF, MMP-3, and Bcl-2 in patients with melanoma. Fifty-one patients with cutaneous melanoma pathologically verified at different stages, and eighteen healthy controls were investigated. Serum VEGF, MMP-3, and Bcl-2 levels were quantitatively analyzed by ELISA. The serum VEGF (P = 0.034) and Bcl-2 (P = 0.005) levels were significantly higher in patients with melanoma than in the control group. However, there was no significant difference in the serum MMP-3 level between melanoma patients and controls (P = 0.51). The serum levels of VEGF were significantly influenced only by Breslow thickness (P = 0.045) and mitosis (0.039) and were not positively correlated with the stage of the disease. Among serum parameters, a significant relationship was found only between serum levels of VEGF and MMP-3 (r = 0.32, P = 0.023). In conclusion, our study demonstrates increased concentrations of VEGF and Bcl-2, but not MMP-3, in serum of melanoma patients regardless of the stage of the disease. VEGF may be a potential endothelial cell growth and survival factor. The mechanism of VEGF regulation of angiogenesis may be in part due to enhanced proliferation and survival of endothelial cells by differential expression of antiapoptotic genes and in part by activation of MMPs.

Prognostic and predictive value of vascular endothelial growth factor and its soluble receptors, VEGFR-1 and VEGFR-2 levels in the sera of small cell lung cancer patients.

OBJECTIVES: Small cell lung cancer (SCLC) has a rapid growth rate and is characterized by early metastases. Tumor growth is dependent on angiogenesis. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Whether surveillance of pre- and post-treatment serum VEGF and especially its receptors VEGF-1 and VEGF-2 levels in SCLC patients have impact on clinical outcome is unknown. METHODS: From February 2001 to January 2003, 39 consecutive patients with histological proven SCLC were enrolled into the study. Pre-treatment (n: 39) and post-treatment (n: 25) samples of the same patients were collected at the time of their response evaluation. The levels of VEGF and its receptors VEGFR-1 and VEGFR-2 were measured in the serum by quantitative sandwich enzyme immunoassay technique. RESULTS: The median pre-treatment serum VEGF, VEGFR-1, and VEGFR-2 levels which were significantly higher than the normal controls were 1,200 pg/ml (range, 1,414.3 +/- 956.2 pg/ml), 85 pg/ml (range, 97.8 +/- 70.7 pg/ml), and 11,550 pg/ml (range, 14,481 +/- 6,267 pg/ml), respectively. We detected a poor but positive correlation between VEGF and VEGFR-2 (r: 0.46, p: 0.003). Pre-treatment low serum VEGF (<728.5 pg/ml) value (p: 0.02) and good response to treatment (p: 0.008) were found as good prognostic factors by multivariate analysis. CONCLUSIONS: Low serum VEGF concentration is a significant and independent prognostic factor in SCLC patients. Surveillance of VEGF and its receptors to predict chemotherapy response is not useful. Whether the levels of serum VEGF and its receptors VEGFR-1 and VEGFR-2 have value in detecting treatment modalities of SCLC need further studies.