Predictive value of MCM5 (ADXBLADDER) analysis in urine of men evaluated for the initial diagnosis of bladder cancer: A comparative prospective study.

BACKGROUND: To compare predictive value of MCM5 to urinary cytology (UC) for the primary diagnosis of bladder cancer (BCa). METHODS: We prospectively enrolled 91 patients who presented macroscopic hematuria or persistent lower urinary tract symptoms at our institution. Single voided mid-stream urine specimens were collected for UC and MCM5 (ADXBLADDER; Arquer Diagnostics Ltd, Sunderland, United Kingdom) assessment. Cystoscopy was used as confirmatory test, and positive cases underwent transurethral resection of bladder tumor with histopathological evaluation. RESULTS: Forty cases (43.9%) showed a positive cystoscopy for BCa. Histology was obtained in 37 cases: 16 (43.2%) high-grade (HG) and 21 (56.8%) low-grade (LG) transitional cell carcinoma (TCC). UC had a sensitivity of 62.5%, specificity of 86.3%, PPV of 78.1% and NPV of 74.6%. Sensitivity, specificity, PPV and NPV of MCM5 were 60.0%, 88.2%, 80.0% and 73.8%, respectively. According to tumor grade, MCM5 and UC showed a sensitivity of 47.6% and 52.4% in LG, and 87.5% and 75.0%, respectively, in HG TCC. False-positive rates were 11.8% and 13.7% of negative cases for BCa with MCM5 and UC test, whereas false-negative results were found in 40.0% and 37.5% of BCa cases, respectively. The combination of the two tests showed a sensitivity of 71.4% in LG, and 93.8% in HG TCC. CONCLUSION: In the present analysis, MCM5 showed lower sensitivity than UC in predicting BCa primary diagnosis. According to tumor grade, MCM5 showed a higher sensitivity in the detection of HG BCa compared to UC, although values were not significantly different.

Evaluation of an Automated CLIA System for the Determination of Carbohydrate Antigen 19-9.

AIM: To compare analytical characteristics between two different methods, a automated chemiluminescent immunoassay (CLIA) versus a radioimmunometric assay (RIA), for the determination of carbohydrate antigen 19-9 (CA19-9). MATERIALS AND METHODS: One hundred and eighty-five blood samples from consecutively enrolled individuals (87 males and 98 females, aged 22-89 and 29-89 years, respectively) were evaluated. For both assays, a cut-off of 37 U/ml was used. RESULTS: Comparison between assays was analyzed using Passing-Bablok regression, which showed a high inter-assay correlation (r=0.926). The mean intra-assay coefficient of variation was 17.6% (range=6.1-50.7%) for the RIA (n=10 samples) and 5.2% (range=0.4-17.0%) for the CLIA assay (n=26 samples). CONCLUSION: This study showed that CLIA for CA19-9 has a good reliability on all samples analyzed and should be preferred to RIA with the aim of reducing costs, greater standardization and more harmonized results.

Protein induced by vitamin K absence or antagonist-II (PIVKA-II) specifically increased in Italian hepatocellular carcinoma patients.

OBJECTIVE: As a marker for Hepatocellular Carcinoma (HCC), Protein Induced by Vitamin K Absence II (PIVKA-II) seems to be superior to alpha fetoprotein (AFP). To better characterize the role of PIVKA-II, both AFP and PIVKA-II have been measured in Italian patients with diagnosis of HCC compared with patients affected by non-oncological liver pathologies. MATERIALS AND METHODS: Sixty serum samples from patients with HCC, 60 samples from patients with benign liver disease and 60 samples obtained from healthy blood donors were included in the study. PIVKA-II and AFP were measured by LUMIPULSE(®) G1200 (Fujirebio-Europe, Belgium). We considered as PIVKA-II cutoff 70 mAU/ml (mean +3SD) of the values observed in healthy subjects. RESULTS: The evaluation of PIVKA-II showed a positivity of 70% in patients with HCC and 5% in patients with benign diseases (p < 0.0001) whereas high levels of AFP were observed in 55% of HCC patients and in 47% of patients with benign diseases. The combined Receiver Operating Characteristic (ROC) analysis of the two analytes revealed a higher sensitivity (75%) compared to those observed for the individual biomarkers. In conclusion, we demonstrate that as a marker for HCC, PIVKA-II is more specific for HCC and less prone to elevation during chronic liver diseases. CONCLUSIONS: The combination of the two biomarkers, evaluated by the ROC analysis, improved the specificity compared to a single marker. These data suggest that the combined analysis of the two markers could be a useful tool in clinical practice.

HE4: a new potential early biomarker for the recurrence of ovarian cancer.

Human epididymis protein 4 (HE4) has recently been described as a new marker for the early diagnosis of ovarian cancer (OC). The objective of this study was to evaluate (a) the expression of HE4 vs. OC mucin CA125 in 32 patients with OC compared to 163 patients with other malignant or benign pathologies (b) HE4 as indicator of the recurrence of the disease in eight patients followed-up for 20 months after OC diagnosis. Serum HE4 and CA 125 levels were determined by ELISA and IRMA, respectively. At diagnosis, the patients with OC demonstrated high levels of both biomarkers with 96.9% sensitivity for HE4 and 85.7% for CA125. In the other pathologies there was 3.7% positivity for HE4 and 21.0% for CA125. The follow-up study showed an increase of HE4 5-8 months before CA125 increment in five of the eight patients, this early expression being strictly associated to a relapse of the disease. In conclusion, this study showed that HE4, compared to CA125, potentially is a better marker for the diagnosis of OC and could be an important early indicator of the recurrence of the disease.