Elif Bilgin

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.

Clinical significance of serum epidermal growth factor receptor (EGFR) levels in patients with breast cancer.

Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of multiple malignancies and its expression strongly also affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of EGFR in breast cancer (BC) patients. A total of 96 patients with a pathologically confirmed diagnosis of BC were enrolled into this study. Serum EGFR levels were determined by the solid-phase sandwich ELISA method. Age and sex matched 30 healthy controls were included in the analysis. Median age of diagnosis was 48years old (range: 29-80). Thirty-seven (39%) consisted of metastatic disease. The baseline serum EGFR levels were significantly higher than in the healthy control group (p<0.001). The serum EGFR concentrations were also significantly higher only in patients with ER-negative and triple-negative tumor (p=0.05 and p=0.04, respectively). The other known clinical variables, including grade of histology, stage of disease, serum CA 15.3 levels, and response to chemotherapy were not found to be correlated with serum EGFR concentrations (p>0.05). Likewise, serum EGFR levels were found to play no prognostic role for survival (p=0.35). In conclusion, while serum EGFR levels were elevated in BC patients, EGFR level has no predictive and prognostic value in these patients.

Serum M65 as a biomarker for metastatic renal cell carcinoma.

INTRODUCTION/BACKGROUND Effective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently need in metastatic RCC. M30 and M65 are released during apoptotic cell death and precisely reflect epithelial tumor cell death. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates for patients with metastatic RCC. PATIENTS AND METHODS Thirty-nine patients with metastatic RCC and 39 healthy control subjects were included in this study. Serum M30 and M65 levels were measured by ELISA. RESULTS The median ages of the patients and control subjects were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and control subjects (53.7 vs. 49.1 U/L; P = .31). The median serum M65 level was significantly higher in patients than in control subjects (334.0 vs. 179.1 U/L; P < .001). Receiver operating characteristic analysis revealed that the best cutoff value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/L. The median PFS of patients whose M65 levels were ≤ 313.6 U/L was better than that of patients whose M65 levels were > 313.6 U/L (P = .03). CONCLUSION To the best of our knowledge, this is the first study to evaluate serum M30 and M65 levels in patients with RCC. Serum M65 levels were significantly elevated in patients with metastatic RCC compared with healthy individuals. In addition, the serum M65 level could be predictive of PFS in patients with RCC.

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.

Clinical significance of serum fibronectin and vitronectin levels in melanoma patients.

Fibronectin and vitronectin are the important components of the extracellular matrix proteins. The aim of this study was to determine the clinical significance of these protein serum levels in patients with melanoma. A total of 60 patients with a pathologically confirmed diagnosis of melanoma were enrolled in this study. Serum fibronectin and vitronectin concentrations were determined using the solid-phase sandwich ELISA method. Thirty age-matched and sex-matched healthy controls were included in the analysis. The baseline serum fibronectin and vitronectin levels were significantly higher in patients with melanoma than those in the healthy control group (P<0.001 and P=0.04, respectively). However, known clinical variables including age of the patient, sex, site of lesion, histology, stage of disease, serum lactate dehydrogenase levels, and response to chemotherapy were not found to be correlated with either serum fibronectin or vitronectin concentrations (P>0.05). Moreover, neither serum fibronectin nor vitronectin levels played a prognostic role in outcome in melanoma patients (P=0.47 and 0.24, respectively). In conclusion, serum levels of both fibronectin and vitronectin may be diagnostic markers in melanoma patients. However, their predictive and prognostic values were not determined.

Clinical significance of serum M30 and M65 levels in metastatic pancreatic adenocarcinoma

M30 and M65 are relatively new assays that detect different circulating forms of the epithelial cell structural protein cytokeratin 18. This study was conducted to investigate the serum levels of M30 and M65 in patients with metastatic pancreatic adenocarcinoma (MPA) and the relationship with tumor progression and known prognostic parameters. Twenty-six patients with MPA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum M30 and M65 levels were determined using enzyme-linked immunosorbent assay. The median age at diagnosis was 59 years, range 32–80 years; 14 patients were men. All patients had metastatic stage, and most (n = 21, 81 %) had hepatic metastasis. The baseline levels of both serum M30 and serum M65 were significantly higher in patients with MPA than those in the control group (p < 0.001, for both assays). Serum M65 level was only significantly higher in the patients with elevated serum LDH levels than in others with normal serum LDH levels (p = 0.03). For serum M30 levels, no correlation was found. The significant relationship was found between the serum levels of M30 and M65 (rs = 0. 926, n = 26, p < 0.001, Spearman’s correlation). The median survival for all patients was 31.7 ± 2.2 weeks (95 % CI = 27.31–36.08). Although only the serum LDH level was found to be a significant prognostic factor (p = 0.01), neither serum M30 nor serum M65 had significant effect on survival (p = 0.28 and p = 0.15, respectively). In conclusion, although both serum levels of M30 and M65 assays were found to be of diagnostic value, no predictive and prognostic values were determined in MPA patients.

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.

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.

Clinical Signifıcance of Serum Ykl-40 (Chitinase-3-Like-1Protein) 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.

Clinical significance of serum claudin-1 levels in melanoma patients.

Claudins are the most important structural and functional components of tight-junction integral membrane proteins. They play roles in major cellular functions including growth and adhesion and are responsible for regulating the paracellular transport of molecules. The objective of this study was to determine the clinical significance of the serum levels of claudin-1, an oldest and important member of the claudin family, in melanoma patients. A total of 98 patients with a pathologically confirmed melanoma were enrolled into this study. Serum claudin-1 concentrations were determined by the solid-phase sandwich enzyme-linked immunosorbent assay method. Age-matched and sex-matched 43 healthy controls were included in the analysis. The median age at diagnosis was 51 years, ranging from 16 to 85 years. The majority of the patients were male (61%) and had axial localized (54%) and metastatic disease (61%). Moreover, most of the patients with metastatic disease had M1c (73%). The baseline serum claudin-1 levels of the melanoma patients were significantly lower than those of control subjects (median values 9.17 vs. 13.82 ng/ml, respectively, P<0.001). However, known clinical variables including age of the patient, sex, site of lesion, histology, lymph node involvement, stage of disease, serum lactate dehydrogenase levels, and response to chemotherapy were not found to be correlated with serum claudin-1 concentrations (P>0.05). Similarly, serum claudin-1 concentration was found to have no prognostic role in survival (P=0.524). In conclusion, serum levels of claudin-1 may have a diagnostic value in melanoma patients. However, its predictive and prognostic value has not been determined.