Chemokine receptor expression in tumour islets and stroma in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>We have previously demonstrated that tumour islet infiltration by macrophages is associated with extended survival (ES) in NSCLC. We therefore hypothesised that patients with improved survival would have high tumour islet expression of chemokine receptors known to be associated with favourable prognosis in cancer. This study investigated chemokine receptor expression in the tumour islets and stroma in NSCLC.</p> <p>Methods</p> <p>We used immunohistochemistry to identify cells expressing CXCR1, CXCR2, CXCR3, CXCR4, CXCR5 and CCR1 in the tumour islets and stroma in 20 patients with surgically resected NSCLC. Correlations were made with macrophage and mast cell expression.</p> <p>Results</p> <p>There was increased expression of CXCR2, CXCR3, and CCR1 in the tumour islets of ES compared with poor survival (PS) patients (p = 0.007, 0.01, and 0.002, respectively). There was an association between 5 year survival and tumour islet CXCR2, CXCR3 and CCR1 density (p = 0.02, 0.003 and <0.001, respectively) as well as stromal CXCR3 density (p = 0.003). There was a positive correlation between macrophage density and CXCR3 expression (r_s= 0.520, p = 0.02) and between mast cell density and CXCR3 expression (r_s= 0.499, p = 0.03) in the tumour islets.</p> <p>Conclusion</p> <p>Above median expression of CXCR2, CXCR3 and CCR1 in the tumour islets is associated with increased survival in NSCLC, and expression of CXCR3 correlates with increased macrophage and mast cell infiltration in the tumour islets.</p

The Tissue Microlocalisation and Cellular Expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 Is Correlated to Clinical Outcome in NSCLC

BACKGROUND: We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM) expression of proteins associated with M1 and M2 macrophages in NSCLC. METHODS: Using immunohistochemistry, CD68(+) macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14), or a non-cytotoxic M2 phenotype (CD163 and VEGF) were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES) (median 92.7 months) and 20 patients with poor survival (PS) (median 7.7 months). RESULTS: The NM expression of NM-HLA-DR (p<0.001), NM-iNOS (p = 0.02) and NM-MRP 8/14 (p = 0.02) was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (p<0.001). There was more NM-CD163 expression (p = 0.04) but less NM-iNOS (p = 0.002) and MRP 8/14 (p = 0.01) expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR p<0.001), 65.0% versus 14.6% (NM-iNOS p = 0.003), and 54.3% versus 22.2% (NM-MRP 8/14 p = 0.04), as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41) and 19.4% versus 59.0% (NM-VEGF p = 0.001). CONCLUSIONS: Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome

Tumour necrosis factor-alpha expression in tumour islets confers a survival advantage in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>The role of TNFα in cancer is complex with both pro-tumourigenic and anti-tumourigenic roles proposed. We hypothesised that anatomical microlocalisation is critical for its function.</p> <p>Methods</p> <p>This study used immunohistochemistry to investigate the expression of TNFα in the tumour islets and stroma with respect to survival in 133 patients with surgically resected NSCLC.</p> <p>Results</p> <p>TNFα expression was increased in the tumour islets of patients with above median survival (AMS) compared to those with below median survival (BMS)(p = 0.006), but similar in the stroma of both groups. Increasing tumour islet TNFα density was a favorable independent prognostic indicator (p = 0.048) while stromal TNFα density was an independent predictor of reduced survival (p = 0.007). Patients with high TNFα expression (upper tertile) had a significantly higher 5-year survival compared to patients in the lower tertile (43% versus 22%, p = 0.01). In patients with AMS, 100% of TNFα⁺cells were macrophages and mast cells, compared to only 28% in the islets and 50% in the stroma of BMS patients (p < 0.001).</p> <p>Conclusions</p> <p>The expression of TNFα in the tumour islets of patients with NSCLC is associated with improved survival suggesting a role in the host anti-tumour immunological response. The expression of TNFα by macrophages and mast cells is critical for this relationship.</p

Abdominal pain in adults with cystic fibrosis.

Abdominal pain is a common symptom in individuals with cystic fibrosis (CF). As prognosis has improved, CF has changed from a pediatric disease to the current situation wherein most people with CF are adults. With improved survival, the spectrum of pathologies causing abdominal pain in CF has shifted. Despite this, there have been relatively few previous publications focusing on gastrointestinal disease in CF adults. The aim of this review was to examine the characteristics, differential diagnosis, investigation, and optimal management of adults with CF presenting with abdominal pain

Kaplan-Meier five year survival curves for non-macrophage densities in the tumour islets for (A) CD163, (B) VEGF, (C) HLA-DR, (D) iNOS and (E) MRP 8/14.

<p>Kaplan-Meier five year survival curves for non-macrophage densities in the tumour islets for (A) CD163, (B) VEGF, (C) HLA-DR, (D) iNOS and (E) MRP 8/14.</p

Patient characteristics.

<p> <i>Plus-minus values are means ± SEM.</i></p><p>*<i>information on resection margins available from 18 Extended Survival patients and 17 Poor Survival patients.</i></p

Non-macrophage double-stain densities in the islets in (A) extended survival (ES) and (B) poor survival (PS).

<p>* represents a significant difference (p<0.05) in expression compared with CD163. <b>∇</b> represents a significant difference (p<0.05) in expression compared with VEGF. <b>†</b> represents a significant difference (p<0.05) between the corresponding marker in the ES group.</p

Kaplan-Meier five year survival curves for non-macrophage densities in the tumour stroma for (A) CD163, (B) VEGF, (C) HLA-DR, (D) iNOS and (E) MRP 8/14.

<p>Kaplan-Meier five year survival curves for non-macrophage densities in the tumour stroma for (A) CD163, (B) VEGF, (C) HLA-DR, (D) iNOS and (E) MRP 8/14.</p

Summary of the cellular distribution results in the tumour islets and stroma indicating the median density of cells/mm² in extended survival (ES) and poor survival (PS) patients.

<p>*p<0.05 compared to islets PS.</p>‡<p>p<0.05 compared to stroma PS.</p