Comparison of tumour-based (Petersen Index) and inflammation-based (Glasgow Prognostic Score) scoring systems in patients undergoing curative resection for colon cancer

After resection, it is important to identify colon cancer patients, who are at a high risk of recurrence and who may benefit from adjuvant treatment. The Petersen Index (PI), a prognostic model based on pathological criteria is validated in Dukes' B and C disease. Similarly, the modified Glasgow Prognostic Score (mGPS) based on biochemical criteria has also been validated. This study compares both the scores in patients undergoing curative resection of colon cancer. A total of 244 patients underwent elective resection between 1997 and 2005. The PI was constructed from pathological reports; the mGPS was measured pre-operatively. The median follow-up was 67 months (minimum 36 months) during which 109 patients died; 68 of them from cancer. On multivariate analysis of age, Dukes' stage, PI and mGPS, age (hazard ratio, HR, 1.74, P=0.001), Dukes' stage (HR, 3.63, P<0.001), PI (HR, 2.05, P=0.010) and mGPS (HR, 2.34, P<0.001) were associated independently with cancer-specific survival. Three-year cancer-specific survival rates for Dukes' B patients with the low-risk PI were 98, 92 and 82% for the mGPS of 0, 1 and 2, respectively (P<0.05). The high-risk PI population is small, in particular for Dukes' B disease (9%). The mGPS further stratifies those patients classified as low risk by the PI. Combining both the scoring systems could identify patients who have undergone curative surgery but are at high-risk of cancer-related death, therefore guiding management and trial stratification

The relationship between the systemic inflammatory response and survival in patients with transitional cell carcinoma of the urinary bladder

The relationship between tumour stage, grade, elevated C-reactive protein concentration (<10/>10 mg l−1), adjuvant therapy and survival was examined in patients with biopsy proven bladder cancer (n=105). On multivariate analysis stage (HR 3.37, 95% CI 1.37–8.29, P=0.008), grade (HR 2.01, 95% CI 1.14–3.57, P=0.017) and preoperative C-reactive protein (HR 3.31, 95% CI 1.09–10.09, P=0.035) were independently associated with cancer-specific survival

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P&lt;0.05) and macrophage (P&lt;0.05) infiltration and microvessel density (P&lt;0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P&lt;0.01), negative hormonal receptor (P&lt;0.10), lower albumin concentrations (P&lt;0.01), increased tumour proliferation (P&lt;0.05), increased tumour microvessel density (P&lt;0.05), the extent of locoregional control (P&lt;0.0001) and limited systemic treatment (Pless than or equal to0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P&lt;0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice

<p>Abstract</p> <p>Background</p> <p>Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level.</p> <p>Methods</p> <p>Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done.</p> <p>Results</p> <p>Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as <it>CCL3</it>, <it>CCL4</it>, <it>CXCL2</it>, and <it>MMP12 </it>in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as <it>S100A8</it>, <it>S100A9 </it>and <it>MMP9</it>.</p> <p>Conclusions</p> <p>Collectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume.</p

An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study

INTRODUCTION: A selective combination of C-reactive protein and albumin (termed the modified Glasgow Prognostic Score, mGPS) has been shown to have prognostic value, independent of tumour stage, in lung, gastrointestinal and renal cancers. It is also of interest that liver function tests such as bilirubin, alkaline phosphatase and gamma-glutamyl transferase, as well as serum calcium, have also been reported to predict cancer survival. The aim of the present study was to examine the relationship between an inflammation-based prognostic score (mGPS), biochemical parameters, tumour site and survival in a large cohort of patients with cancer. METHODS: Patients (n = 21 669) who had an incidental blood sample taken between 2000 and 2006 for C-reactive protein, albumin and calcium (and liver function tests where available) and a diagnosis of cancer were identified. Of this group 9608 patients who had an ongoing malignant process were studied (sampled within 2 years before diagnosis). Also a subgroup of 5397 sampled at the time of diagnosis (sampled within 2 months prior to diagnosis) were examined. Cancers were grouped by tumour site in accordance with International Classification of Diseases 10 (ICD 10). RESULTS: On follow up, there were 6005 (63%) deaths of which 5122 (53%) were cancer deaths. The median time from blood sampling to diagnosis was 1.4 months. Increasing age, male gender and increasing deprivation was associated with a reduced 5-year overall and cancer-specific survival (all P &lt; 0.001). An elevated mGPS, adjusted calcium, bilirubin, alkaline phosphatase, aspartate transaminase, alanine transaminase and gamma-glutamyl transferase were associated with a reduced 5-year overall and cancer-specific survival (independent of age, sex and deprivation in all patients sampled), as well as within the time of diagnosis subgroup (all P &lt; 0.001). An increasing mGPS was predictive of a reduced cancer-specific survival in all cancers (all P &lt; 0.001). CONCLUSION: The results of the present study indicate that the mGPS is a powerful prognostic factor when compared with other biochemical parameters and independent of tumour site in patients with cancer

The inflammatory microenvironment in colorectal neoplasia

Peer reviewedPublisher PD

TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM) on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta) signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited.</p> <p>Methods</p> <p>Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4) in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2) vs. high-grade (i.e. grade 3 and 4)), lymph node metastasis, distant metastasis, 5 year cancer related survival) using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed.</p> <p>Results</p> <p>High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and shorter survival. Stromal TGF-beta receptor 2 expression was an independent prognostic factor for cancer related survival.</p> <p>Conclusion</p> <p>Histological phenotype and clinical behaviour of colon cancer is not only influenced by mutational incidents in tumour cells but also affected by interaction of tumour tissue with inflammatory cells like macrophages and associated stroma and TGF-beta signalling is one important part of this crosstalk. Further studies are needed to elucidate the exact mechanisms.</p