Cancer Biomarkers

The purpose of this study was to evaluate the diagnostic efficacy of urinary transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) in comparison with voided urine cytology in the detection of bladder cancer. This study included 120 patients with bladder cancer, 54 patients with benign urological disorders and 55 healthy volunteers. Urine supernatant was used for estimation of TGF-β1 and VEGF by ELISA. VEGF was detected by Western blot (WB) analysis in the urine supernatant of randomly selected bladder cancer patients. The urine sediment was used for cytology. There was a statistically significant difference in the median levels of TGF-β1 (P=0.002) and VEGF (P=0.000) between the control, benign and malignant groups. The concordance rate of VEGF ELISA with VEGF WB was 96.3%. The overall sensitivity and specificity were 70.8% and 90.8% for voided urine cytology, 71.6% and 59.6% for TGF-β1, and 76.7% and 61.5% for VEGF. The combined use of voided urine cytology with TGF-β1 and VEGF improved the sensitivity up to 94.9%, although it lowered specificity to 62.0%. There was a significant association between positivity rate of TGF-β1 and positive urine cytology samples (P=0.023). Median level and positivity rate of VEGF were significantly associated with early stage (I, II) of bladder carcinoma (P=0.01 and 0.025, respectively). Our data indicate that urinary TGF-β1 and VEGF had higher sensitivities compared to voided urine cytology. Moreover, the combined sensitivity of voided urine cytology with TGF-β1 and VEGF together was higher than sensitivity of voided urine cytology alone in detection of bladder cancer.

SMRP (soluble mesothelin-related peptides) is a promising marker for detection of malignant mesotheliomas (MM) in serum that has not yet been validated in appropriate epidemiological studies. Field studies might not always provide optimal conditions for storage and transport of samples, and follow-up studies have to rely on sample integrity. Proper validation of the marker would require sufficient stability of the antigen and robustness of the assay. SMRP concentrations were evaluated in serum samples of 98 healthy donors, using the MESOMARK ELISA kit. The SMRP distribution in the healthy study population was determined and biological and pre-analytical variations were examined regarding their influence on SMRP concentrations. For diagnostic decisions a best statistical and unbiased cut-off between 1.5 and 1.6 nmol/L was determined (95th percentile). No age- or gender-specific differences could be observed. SMRP exhibits excellent stability regarding short-term storage, long-term storage, and repeated freeze/thaw cycles. Scientific studies as well as real life applications that employ SMRP would not be limited by sample stability issues.

A number of studies have demonstrated that high tumor tissue levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) are associated with a poor prognosis in breast cancer, suggesting that TIMP-1 could be a valid prognostic marker in this disease. Recently, our laboratories have presented results showing that TIMP-1 also carries prognostic information when measured in serum. This is an important finding, since serum is a much more preferable material compared with tumor tissue extracts. The aim of the present study was to validate the previous results concerning the prognostic value of TIMP-1 in serum obtained preoperatively from 68 patients with primary breast cancer. This was done by measuring the same serum samples as in the previous study but in a different laboratory using a different ELISA assay. We confirmed that patients with the highest serum levels of TIMP-1 (> 197.7 ng/ml) had significantly shorter disease-specific survival compared with patients with low serum TIMP-1 levels. In the group of node-negative patients, 53% of the patients with high levels of TIMP-1 survived after 10 years of follow-up compared to 92% of the patients with low levels. This study thus confirms the reproducibility across laboratories of the results concerning the prognostic value of TIMP-1 in serum. We also investigated whether measurements of the specific fraction of uncomplexed TIMP-1 improved the prognostic value of TIMP-1 in serum, as has been shown to be the case for tumor tissue extracts. However, including information of the level of uncomplexed TIMP-1 did not seem to provide additional prognostic information to that already provided by total TIMP-1.

Over the past four decades in the United States, there has been a divergent trend in mortality rates between African-Americans and Caucasians with colorectal cancer (CRC). Rates among Caucasians have been steadily declining, whereas rates among African-Americans have only started a gradual decline in recent years. We reviewed epidemiologic studies of CRC racial disparities between African-Americans and Caucasians, including studies from SEER and population-based cancer registries, Veterans Affairs (VA) databases, healthcare coverage databases, and university and other medical center data sources. Elevated overall and stage-specific risks of CRC mortality and shorter survival for African-Americans compared with Caucasians were reported across all data sources. The magnitude of racial disparities varied across study groups, with the strongest associations observed in university and non-VA hospital-based medical center studies, while an attenuated discrepancy was found in VA database studies. An advanced stage of disease at the time of diagnosis among African-Americans is a major contributing factor to the racial disparity in survival. Several studies, however, have shown that an increased risk of CRC death among African-Americans remains even after controlling for tumor stage at diagnosis, socioeconomic factors, and co-morbidity. Despite advances in treatment, improvements in the standard of care, and increased screening options, racial differences persist in CRC mortality and survival. Therefore, continued research efforts are necessary to disentangle the clinical, social, biological, and environmental factors that constitute the racial disparity. In addition, results across data sources should be considered when evaluating racial differences in cancer outcomes.

The chronic myeloproliferative disorders (CMPDs) are a heterogeneous group of clonal hematopoietic diseases characterized by production of increased numbers of mature leukocytes, erythrocytes, and/or platelets. Clinically these disorders are often insidious in onset, produce nonspecific thrombotic or hemorrhagic complications, and can be easily confused with a variety of benign, reactive conditions. Thus, confirming a CMPD can be difficult as it is often a diagnosis of exclusion. The recently identified JAK2^V617F mutation is frequently present in the classic CMPDs polycythemia vera, essential thrombocythemia, and chronic idiopathic myelofibrosis. JAK2^V617F determination has proven to be a useful diagnostic tool in patients with some clinical features suggestive for a CMPD, and may have benefit as a way to monitor known disease. There are several published molecular assays for the JAK2^V617F target, of variable sensitivity and technical complexity, many of which are not easily replicated in a typical clinical laboratory. We present a robust, sensitive PCR/melt curve assay for the JAK2^V617F mutation which uses the widely available Roche LightCycler® platform, and is thus applicable to many clinical molecular laboratories.