Prognostic value of microvessel density in stage II and III colon cancer patients:a retrospective cohort study

Background Microvessel density (MVD), as a derived marker for angiogenesis, has been associated with poor outcome in several types of cancer. This study aimed to evaluate the prognostic value of MVD in stage II and III colon cancer and its relation to tumour-stroma-percentage (TSP) and expression of HIF1A and VEGFA. Methods Formalin-fixed paraffin-embedded (FFPE) colon cancer tissues were collected from 53 stage II and 54 (5-fluorouracil-treated) stage III patients. MVD was scored by digital morphometric analysis of CD31-stained whole tumour sections. TSP was scored using haematoxylin-eosin stained slides. Protein expression of HIF1A and VEGFA was determined by immunohistochemical evaluation of tissue microarrays. Results Median MVD was higher in stage III compared to stage II colon cancers (11.1% versus 5.6% CD31-positive tissue area, p <0.001). High MVD in stage II patients tended to be associated with poor disease free survival (DFS) in univariate analysis (p = 0.056). In contrast, high MVD in 5FU-treated stage III patients was associated with better DFS (p = 0.006). Prognostic value for MVD was observed in multivariate analyses for both cancer stages. Conclusions MVD is an independent prognostic factor associated with poor DFS in stage II colon cancer patients, and with better DFS in stage III colon cancer patients treated with adjuvant chemotherapy

Bioenergy II: Biomass Valorisation by a Hybrid Thermochemical Fractionation Approach

The need for green renewable sources is adamant because of the adverse effects of the increasing use of fossil fuels on our society. Biomass has been considered as a very attractive candidate for green energy carriers, chemicals and materials. The development of cheap and efficient fractionation technology to separate biomass into its main constituents is highly desirable. It enables treatment of each constituent separately, using dedicated conversion technologies to get specific target chemicals. The synergistic combination of aquathermolysis (hot pressurised water treatment) and pyrolysis (thermal degradation in the absence of oxygen) is a promising thermolysis option, integrating fractionation of biomass with production of valuable chemicals. Batch aquathermolysis in an autoclave and subsequent pyrolysis using bubbling fluidised bed reactor technology with beech, poplar, spruce and straw indicate the potential of this hybrid concept to valorise lignocellulosic biomass. Hemicellulose-derived furfural was obtained in yields that ranged from 2 wt% for spruce to 8 wt% for straw. Hydroxymethylfurfural from hemicellulose was obtained in yields from 0.3 wt% for poplar to 3 wt% for spruce. Pyrolysis of the aquathermolised biomass types resulted in 8 wt% (straw) to 11 wt% (spruce) of cellulose-derived levoglucosan. Next to the furfurals and levoglucosan, appreciable amounts of acetic acid were obtained as well from the aquathermolysis step, ranging from 1 wt% for spruce to 5 wt% for straw. To elucidate relations between the chemical changes occurring in the biomass during the integrated process and type and amount of the chemical products formed, a 13C-solid state NMR study has been conducted. Main conclusions are that aquathermolysis results in hemicellulose degradation to lower molecular weight components. Lignin ether bonds are broken, but apart from that, lignin is hardly affected by the aquathermolysis. Cellulose is also retained, although it seems to become more crystalline, probably due to a higher ordering of amorphous cellulose when the samples are cooled down after aquathermolysis. These NMR results are in agreement with thermogravimetric analyses results.

Bioenergy in Europe:Implementation of EU directives and policies relating to bioenergy in Europe and RD&amp;D priorities for the future

VTT Research Notes Series no. 2441The study carried out within the Bioenergy Network of Excellence analyzes the implementation of important EU directives and policies relating to bioenergy in Europe to identify major RD&D needs in the field. Major EU directives, commonly known as the Promotion of Renewable Electricity, Biofuels and Landfill Directives, along with the EU Emissions Trading Scheme and parts of the Common Agricultural Policy, are some of the most important drivers behind the growth of bioenergy in the EU27 today. The report compares how Germany, Finland and the Netherlands have implemented the directives, examining the policy frameworks in each country and the plans and mechanisms in place to reach national targets. A wider European perspective for each directive is then drawn out, and recommendations for RD&D actions to meet the EU directive targets or obligations in each area are outlined. The report also takes a broader look at the effects the EU Emissions Trading Scheme and the Common Agricultural Policy are having on the use of biomass in the EU with RD&D recommendations for each area. Bioenergy NoE advocates stronger communication and cooperation among various EUwide projects and initiatives focusing on bioenergy development. Industry commitment to RD&D projects is, however, the only direct path for bringing stateoftheart technology and products to market. Building sustainable production pathways and addressing competition with food products is crucial to developing environmentallysound biofuels. Research in renewable electricity from biomass should prioritize development of higher efficiency power production and powertoheat ratios in combined heat and power plants over new technology development. In the biofuels field, RD&D should prioritize the development of more sustainable, second generation biofuels. To meet landfill diversion targets, thermal conversion and energy recovery of municipal solid waste in some EU countries will have to increase. Meeting the European targets set for 2020 requires significant technology development in order to introduce a new generation of biofuels and feedstocks: this is the focus for Bioenergy NoE RD&D

Quantitative analysis of CDX2 protein expression improves its clinical utility as a prognostic biomarker in stage II and III colon cancer

Aim: Better stratification of patients with stage II and stage III colon cancer for risk of recurrence is urgently needed. The present study aimed to validate the prognostic value of CDX2 protein expression in colon cancer tissue by routine immunohistochemistry and to evaluate its performance in a head-to-head comparison with tandem mass spectrometry–based proteomics. Patient and methods: CDX2 protein expression was evaluated in 386 stage II and III primary colon cancers by immunohistochemical staining of tissue microarrays and by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis using formalin-fixed paraffin-embedded tissue sections of a matched subset of 23 recurrent and 23 non-recurrent colon cancers. Association between CDX2 expression and disease-specific survival (DSS) was investigated. Results: Low levels of CDX2 protein expression in stage II and III colon cancer as determined by immunohistochemistry was associated with poor DSS (hazard ratio [HR] = 1.97 (95% confidence interval [CI]: 1.26–3.06); p = 0.002). Based on analysis of a selected sample subset, CDX2 prognostic value was more pronounced when detected by LC-MS/MS (HR = 7.56 (95% CI: 2.49–22.95); p < 0.001) compared to detection by immunohistochemistry (HR = 1.60 (95% CI: 0.61–4.22); p = 0.34). Conclusion: This study validated CDX2 protein expression as a prognostic biomarker in stage II and III colon cancer, conform previous publications. CDX2 prognostic value appeared to be underestimated when detected by routine immunohistochemistry, probably due to the semiquantitative and subjective nature of this methodology. Quantitative analysis of CDX2 substantially improved its clinical utility as a prognostic biomarker. Therefore, development of routinely applicable quantitative assays for CDX2 expression is needed to facilitate its clinical implementation

Quantitative analysis of CDX2 protein expression improves its clinical utility as a prognostic biomarker in stage II and III colon cancer

Aim: Better stratification of patients with stage II and stage III colon cancer for risk of recurrence is urgently needed. The present study aimed to validate the prognostic value of CDX2 protein expression in colon cancer tissue by routine immunohistochemistry and to evaluate its performance in a head-to-head comparison with tandem mass spectrometry–based proteomics. Patient and methods: CDX2 protein expression was evaluated in 386 stage II and III primary colon cancers by immunohistochemical staining of tissue microarrays and by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis using formalin-fixed paraffin-embedded tissue sections of a matched subset of 23 recurrent and 23 non-recurrent colon cancers. Association between CDX2 expression and disease-specific survival (DSS) was investigated. Results: Low levels of CDX2 protein expression in stage II and III colon cancer as determined by immunohistochemistry was associated with poor DSS (hazard ratio [HR] = 1.97 (95% confidence interval [CI]: 1.26–3.06); p = 0.002). Based on analysis of a selected sample subset, CDX2 prognostic value was more pronounced when detected by LC-MS/MS (HR = 7.56 (95% CI: 2.49–22.95); p < 0.001) compared to detection by immunohistochemistry (HR = 1.60 (95% CI: 0.61–4.22); p = 0.34). Conclusion: This study validated CDX2 protein expression as a prognostic biomarker in stage II and III colon cancer, conform previous publications. CDX2 prognostic value appeared to be underestimated when detected by routine immunohistochemistry, probably due to the semiquantitative and subjective nature of this methodology. Quantitative analysis of CDX2 substantially improved its clinical utility as a prognostic biomarker. Therefore, development of routinely applicable quantitative assays for CDX2 expression is needed to facilitate its clinical implementation

Loss of KCNQ1 expression in stage II and stage III colon cancer is a strong prognostic factor for disease recurrence

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Accurately identifying stage II CRC patients at risk for recurrence is an unmet clinical need. KCNQ1 was previously identified as a tumour suppressor gene and loss of expression was associated with poor survival in patients with CRC liver metastases. In this study the prognostic value of KCNQ1 in stage II and stage III colon cancer patients was examined. METHODS: KCNQ1 mRNA expression was assessed in 90 stage II colon cancer patients (AMC-AJCCII-90) using microarray gene expression data. Subsequently, KCNQ1 protein expression was evaluated in an independent cohort of 386 stage II and stage III colon cancer patients by immunohistochemistry of tissue microarrays. RESULTS: Low KCNQ1 mRNA expression in stage II microsatellite stable (MSS) colon cancers was associated with poor disease-free survival (DFS) (P=0.025). Loss of KCNQ1 protein expression from epithelial cells was strongly associated with poor DFS in stage II MSS (P<0.0001), stage III MSS (P=0.0001) and stage III microsatellite instable colon cancers (P=0.041). KCNQ1 seemed an independent prognostic value in addition to other high-risk parameters like angio-invasion, nodal stage and microsatellite instability-status. CONCLUSIONS: We conclude that KCNQ1 is a promising biomarker for prediction of disease recurrence and may aid stratification of patients with stage II MSS colon cancer for adjuvant chemotherapy