Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology

BACKGROUND: Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. OBJECTIVE: To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. RESULTS AND LIMITATIONS: A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation. CONCLUSIONS: The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. PATIENT SUMMARY: The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population

International Comparison CCQM-K51 - Carbon Monoxide (CO) in Nitrogen (5 µmol mol-1)

The first key comparison on carbon monoxide (CO) in nitrogen dates back to 1992 (CCQM-K1a). It was one of the first types of gas mixtures that were used in an international key comparison. Since then, numerous national metrology institutes (NMIs) have been setting up facilities for gas analysis, and have developed claims for their Calibration and Measurement Capabilities (CMCs) for these mixtures. Furthermore, in the April 2005 meeting of the CCQM (Consultative Committee for Amount of Substance) Gas Analysis Working Group, a policy was proposed to repeat key comparisons for stable mixtures every 10 years. This comparison was performed in line with the policy proposal and provided an opportunity for NMIs that could not participate in the previous comparison. NMISA from South Africa acted as the pilot laboratory. Of the 25 participating laboratories, 19 (76%) showed satisfactory degrees of equivalence to the gravimetric reference value. The results show that the CO concentration is not influenced by the measurement method used, and from this it may be concluded that the pure CO, used to prepare the gas mixtures, was not 13C-isotope depleted. This was confirmed by the isotope ratio analysis carried out by KRISS on a 1% mixture of CO in nitrogen, obtained from the NMISA. There is no indication of positive or negative bias in the gravimetric reference value, as the results from the different laboratories are evenly distributed on both sides of the key comparison reference value.JRC.H.2-Air and Climat

Key comparison for measurement of stack gas CCQM-K71 Final report

77 f. : il.Industrial stack gas emission measurements are important for process control, control of air pollution, and for implementing legislation regarding the carbon dioxide emission rights. Measurements are typically performed using a range of process analysers for carbon monoxide (CO), carbon dioxide (CO2), nitrogen oxides (NOx), sulphur dioxide (SO2) and miscellaneous hydrocarbons. The calibration of these analysers is often performed using a series of binary mixtures of each component in nitrogen. For reasons of efficiency as well as a better match with true stack gas, the use of multicomponent mixtures for this purpose would be preferred. The measurement of stack gas is a challenging task, as the various components may interfere in the measurement of other components. The challenge for the participating national metrology institutes is to control these interferences during the measurement (characterisation) of the mixtures in this international key comparison. Binary mixtures have been part of previous key comparisons, such as CCQM-K1 [1] (carbon monoxide, carbon dioxide, nitrogen monoxide, and sulphur dioxide) and CCQM-K52 (carbon dioxide) [2]. Carbon monoxide, carbon dioxide and propane have also been the subject of a key comparison in the form of a multicomponent mixture: CCQM-K3 [3] (automotive mixtures). Just as in other key comparisons in gas analysis, the values as obtained from gravimetric preparation in accordance with ISO 6142 [4] are taken as the reference values

International comparison CCQM-K76 : sulfur dioxide in nitrogen

85 p. : il.This Key Comparison is designed to test the capabilities of the participants to measure and certify sulfur dioxide in nitrogen, and will provide supporting evidence for the CMCs of institutes for sulfur dioxide. Also, as sulfur dioxide is designated a core compound, and the 100 μmol/mol concentration is within the designated core compound concentration range, this comparison is also designed to demonstrate core capabilities of institutes which qualify under the rules of the Gas Analysis Working Group