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Background/aim Approximately 20% of pleural effusions are associated with cancer; about 50% require invasive procedures to perform diagnosis. Determination of the concentration of soluble cytokeratin 19-fragments (CYFRA21-1) may help identify patients with malignant effusions. However, pathologies other than cancer can increase its concentration. The identification of these possible false positives with routine tests CRP, ADA, % polymorphonuclear cells (PN) may improve diagnostic accuracy. This study aimed to determine the diagnostic accuracy of CYFRA21-1 in the detection of malignant pleural effusions and the possible false positives. Materials and methods Analysis of CYFRA21-1, adenosine deaminase (ADA), C-reactive protein (CRP), and the percentage of polymorphonuclear leukocytes (PN%) in the fluid from 643 consecutive undiagnosed pleural effusions was performed. Results CYFRA21-1 showed 38.7% sensitivity and 97.3% specificity at 175 ng/ml cut-off. Effusions not suspicious of a false-positive showed 39.0% sensitivity and 98.2% specificity, while effusions suspicious of false positive showed lower sensitivity (36.4%) and specificity (95.0%). Conclusion The diagnostic accuracy of CYFRA21-1 in pleural effusions can be improved by classification according to the possibility of false positives.

AIM To confirm that the carbohydrate antigen 19.9 (CA 19.9) protein can be evaluated by determining changes in the β2 zone in protein electrophoresis. MATERIALS AND METHODS A total of 75 patients (64 with cancer, 11 with benign diseases) with abnormal serum CA 19.9 level were included. RESULTS Patients with cancer had significantly higher serum CA 19.9 concentrations than those with benign diseases (p

BACKGROUND/AIM Approximately 10% of patients are unable to synthesize CA 19.9 (Lewis-negative), and these results are erroneously considered false-negatives. The aim of this study was to confirm that CA 19.9 cannot be detected by immunoassays in Lewis-negative patients. MATERIALS AND METHODS CA 19.9 levels were measured by immunological assays and Lewis phenotype was determined by the haemagglutination reaction. RESULTS Patients with Lewis phenotype (a+b-) or (a-b+) had significantly higher CA 19.9 levels than Lewis-negative patients with active cancer (p

The usefulness of tumor markers in the differential diagnosis of cancer in patients with ascites remains a matter of controversy. Few studies have reported the measurement of cancer antigen 125 (CA125) and cytokeratin 19 soluble fragments (CYFRA21-1) in ascitic fluid. The aim of the present study was to evaluate the diagnostic accuracy of these tumor markers in the detection of malignant ascites.We analyzed CA125 and CYFRA21-1 from 143 consecutive undiagnosed patients with ascitis.Use of CA125 gave a sensitivity of 39.7% and a specificity of 98.8%, and CYFRA21-1 a sensitivity of 50.0% and a specificity of 97.6% in differential diagnosis of malignant ascites. For combined use of CA125 plus CYFRA21-1, sensitivity was 65.5% and specificity 96.5%. In patients with negative cytology, these two tumor markers had a sensitivity of 50% and a specificity of 96.5%.The determination of tumor markers in ascitic fluid could be useful for the diagnostic assessment of patients with ascites.

We performed a laboratory and clinical evaluation of Kroma iT (Linear Chemicals S.L), an immunoturbidimetric analyzer for the detection of fecal occult blood.After a familiarization period, the imprecision, linearity of dilution and carry-over were determined and a clinical evaluation was performed on 210 patients.Within-run imprecision ranged between 1.06% and 8.04%. Between-run imprecision ranged between 3.11% and 13.09%. Linearity of dilution revealed a mean recovery of all dilutions of 95.24%, with a standard deviation of 7.47%. No carry-over was detected. The clinical evaluation demonstrated that the mean hemoglobin levels of the fecal immunochemical test values from patients with advanced neoplasms (colorectal cancer plus advanced adenoma) were significantly higher than those of cases with a normal colonoscopy examination. Sensitivity for advanced neoplasms at cut-off values between 80 and 300 ng/ml (6.4-24 mg Hb/Kg feces) ranged from 45.5% to 36.4% and the specificity ranged from 86.8% to 92.3%. The positive predictive values for detecting colorectal cancer and advanced adenomas were 5.4-6.4% and 27-34% respectively and the negative predictive value ranged from 92.5% to 91.7%. Using two samples per patient, a substantial increase of sensitivity was observed, with only a slight decrease in specificity.Kroma iT analyzer is easy to handle and safe for personnel to use. Its analytical and clinical performance makes it suitable for use in a clinical chemistry laboratory for the early detection of advanced neoplasms.

The usefulness of interleukin 6 (IL-6) and its soluble receptor IL-6sR in the prediction of the biochemical recurrence was evaluated in patients with prostate cancer treated with radical prostatectomy.IL-6 and sIL-6R serum levels were measured in 96 patients with prostate cancer.Using the log-rank test, it was evident that patients with preoperative serum levels of IL-6 higher than 1.2 pg/ml had a significantly increased probability of biochemical recurrence (p=0.031). We also observed that the Gleason score was associated with the risk of progression (p=0.033), but no relation was observed with TNM classification, PSA, % free PSA or sIL-6R. In a multivariate analysis, only IL-6 serum levels remained as a predictor of biochemical recurrence (p=0.040).The results presented here demonstrated the usefulness of IL-6 in predicting the biochemical progression of prostate cancer, pointing towards an association between inflammation and the aggressiveness of the tumor.

The diversity of the Mediterranean diet and the heterogeneity of acquired epigenetic alterations in colorectal cancer (CRC) led us to examine the possible association between dietary factors and promoter hypermethylation in genes implicated in the pathogenesis of these neoplasms (p16(INK4a), p14(ARF), hMLH1) and the interaction with methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism.For the molecular study, 120 CRC patients were analyzed for hMLH1 promoter methylation status and MTHFR genotyping. Dietary patterns and molecular data on p16(INK4a) and p14(ARF) methylation were obtained from previous studies with this populations.Patients with methylation in p16(INK4a) consumed significantly less folate (p = 0.01), vitamin A (p = 0.01), vitamin B1 (p = 0.007), potassium (p = 0.03) and iron (p = 0.02) than controls. Patients with methylation in p14(ARF) or hMLH1 consumed significantly less vitamin A (p = 0.001 and p = 0.05, respectively).These results support that certain micronutrients protect against colorectal neoplasia and emphasize the importance of considering the different molecular forms of CRC as etiologically distinct diseases.

Free prostate-specific antigen (fPSA), the minor form of total PSA, contains different molecular subforms, including BPSA and proPSA. Whereas BPSA is associated with benign prostate hyperplasia, proPSA is associated with prostate tumor.The serum levels of PSA, fPSA and proPSA were measured using automated electrochemiluminescent immunoassays (Elecsys 2010, Roche Diagnostics) in 87 patients with prostate cancer and 138 patients with benign prostate hyperplasia. Also, we calculated the derived tests of these assays through the subtraction or the ratio between the measured tests.Receiver operating characteristics curves were used for comparison of the diagnostic utility of tests assessed. The biggest areas were obtained for the free/total PSA ratio (0.705), the calculated Bfree PSA/total PSA ratio (0.719) and the calculated Bfree PSA/bound PSA ratio (0. 726).Applying a multivariate logistic regression analysis, it was determined that the combination of the proPSA concentration, the proPSA/total PSA ratio and the calculated Bfreeltotal PSA ratio improves the area under the curve obtained for individual tests (0.753). ProPSA may be useful in the diagnosis of prostate cancer.

The serum levels of CYFRA 21.1, CEA and SCC were prospectively determined in 156 patients diagnosed with carcinoma of the uterine cervix from 1995 to 2003. Histology revealed squamous cancer in 119 patients, adenocarcinoma in 25 patients and adenosquamous carcinoma in the remaining 12 patients. We considered 3.3 ng/ml, 5 ng/ml and 2 ng/ml as the upper limits of normality for CYFRA 21.1, CEA and SCC, respectively. The sensitivity of CYFRA 21.1, CEA and SCC was 26%, 25% and 43%, respectively, at diagnosis. SCC was clearly related to tumor histology, with significantly higher levels in squamous tumors than in other histological types (p0.0001). The relationship of CEA with the histological type was poor, but the highest concentrations were found in adenocarcinomas (p=0.034). All the tumor markers were related to well known prognostic factors such as tumor size, tumor stage, parametrial invasion and nodal involvement. Abnormal pretreatment serum levels indicated a high probability (83%) of parametrial invasion in squamous tumors. Likewise, pretreatment SCC and CYFRA 21.1 serum levels were of prognostic value, with a shorter DFS and OS in patients with abnormal levels. Multivariate analysis indicated that stage, histological grade and parametrial invasion were independent prognostic factors, but not tumor markers. In conclusion, SCC is the tumor marker of choice in squamous tumors and the addition of CEA or CYFRA 21.1 does not significantly increase the sensitivity obtained by using SCC alone.

We studied the specificity and sensitivity of progastrin releasing peptide (ProGRP) in 37 healthy subjects and 195 patients with benign and 149 with malignant diseases other than lung cancer. Likewise, we compared the ProGRP with other tumor markers used in lung cancer (CEA, SCC, CYFRA and NSE) in 187 patients with NSCLC and in 66 SCLC patients. We considered 50 pg/ml, 5 ng/ml, 2 ng/ml, 3.3 ng/ml and 20 ng/ml as the upper limits of normality for ProGRP, CEA, SCC, CYFRA 21-1 and NSE, respectively. Abnormal ProGRP serum levels were found in 10% of patients with benign diseases and in 13% of patients with malignancies other than lung. Renal failure was the main source of false-positive results (51.6%). Slightly raised ProGRP serum levels, excluding renal failure, were found in 4.1% of patients with benign diseases (80 pg/ml) and in 5% of patients with malignancies other than lung cancer or neuroendocrine tumors (120 pg/ml). Abnormal levels of ProGRP, NSE, CEA, CYFRA and SCC were found in 30%, 22.5%, 55.6%, 65.2% and 26.7% of NSCLC and in 73%, 64%, 53%, 46% and 4.5% of SCLC, respectively. Tumor marker serum levels were related to histological type and tumor extension, with ProGRP being the most sensitive marker in SCLC, CEA in adenocarcinomas and CYFRA 21-1 in squamous tumors. The most sensitive combinations of tumor markers were ProGRP and NSE in SCLC (88%), and CEA plus CYFRA in NSCLC (82%). In summary, ProGRP is the tumor marker of choice in SCLC and NSE is a complementary tumor marker in this histological type.

The description of a new method for the measurement of complexed prostate-specific antigen (cPSA) offers a new approach to the diagnosis of prostate cancer.We measured PSA (Hybritech and Bayer), free PSA (Hybritech) and complexed PSA (Bayer) in 72 patients with prostate cancer and 128 with benign prostate hyperplasia.We found an increase of sensitivity using 25 and 7 ng/mL as cut-offs for cPSA in relation to total PSA using as cut-offs 4 and 10 ng/mL (96 and 36% vs. 92 and 35.5%). Similar differences were found for specificity (78% and 31% for cPSA vs. 73% and 29% for total PSA). Therefore, we defined a gray zone for patients with cPSA between 2.5 and 7 ng/mL for which the measurement of the free/complexed PSA ratio saves an important number of negative biopsies maintaining a higher sensitivity.