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. 2008 Nov 4;99(9):1476-83.
doi: 10.1038/sj.bjc.6604713. Epub 2008 Oct 14.

The prognostic impact of NF-kappaB p105, vimentin, E-cadherin and Par6 expression in epithelial and stromal compartment in non-small-cell lung cancer

S Al-Saad  1 , K Al-Shibli, T Donnem, M Persson, R M Bremnes, L-T Busund
Affiliations

The prognostic impact of NF-kappaB p105, vimentin, E-cadherin and Par6 expression in epithelial and stromal compartment in non-small-cell lung cancer

S Al-Saad et al. Br J Cancer. .

Abstract

Vimentin, nuclear factor-kappaB (NF-kappaB) p105, fascin, E-cadherin, TGF-beta, Par6 and atypical PKC are molecular markers that play an important role in cell differentiation. Herein, we investigate their prognostic impact in primary non-small-cell carcinoma (NSCLC). Tumour tissue samples from 335 resected patients with stage I-IIIA were used. Tissue microarrays were constructed from duplicate cores of both neoplastic cells and stromal cells and were immunohistochemically evaluated. In univariate analyses, high tumour epithelial cell expressions of NF-kappaB p105 (P=0.02) and E-cadherin (P=0.03) were positive prognostic indicators for disease-specific survival (DSS), whereas high tumour epithelial cell expression of vimentin (P=0.001) was a negative prognostic indicator. High expression of NF-kappaB p105 (P=0.001) and Par6 (P=0.0001) in the stromal compartment correlated with a good prognosis. In multivariate analyses, the tumour epithelial cell expression of NF-kappaB p105 (P=0.0001) and vimentin (P=0.005) and the stromal cell expression of NF-kappaB p105 (P=0.007) and Par6 (P=0.0001) were independent prognostic factors for DSS. High expression of NF-kappaB p105 and low expression of vimentin in tumour epithelial cells are independent predictors of better survival in primary NSCLC. In stromal cells, high expressions of NF-kappaB p105 and Par6 are both favourable independent prognostic indicators.

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Figures

Figure 1
Figure 1
Simplified schematic illustration of signals regulating cell differentiation. (A) Polarised normal epithelium cells with tight junctions between cells resting on the basement membrane. (B) Different risk factors (including cigarette smoke, toxins and genetic factors) can cause activation of different oncogenes, which regulate cell differentiation. Activation of receptor tyrosine kinases (RTKs) is known to play a role in inducing mesenchymal phenotype. (C) Unpolarised spindle-shaped epithelial cells with loss of tight junctions and upregulation of mesenchymal markers like vimentin and fascin. TGF-β=transforming growth factor-β; TGF-βR=transforming growth factor-beta receptor; RAS=rat sarcoma oncogene; NF-κB=nuclear factor-κB; AKT/PKB=AKT/protein kinase B; Par6=partitioning-defective protein-6; aPKC=atypical protein kinase C.
Figure 2
Figure 2
Immunohistochemical analysis of TMA of NSCLC representing different EMT markers including (A) NF-κB p105 and (B) E-cadherin in tumour as well as (C) NF-κB p105 and (D) Par6 in stromal cells. NF-κB=nuclear factor-κB; NSCLC=non-small-cell carcinoma; TMA=tissue microarray.
Figure 3
Figure 3
Disease-specific survival curves for tumour epithelial cell NF-κB p105, vimentin and E-cadherin. NF-κB=nuclear factor-κB.
Figure 4
Figure 4
Disease-specific survival curves for stromal NF-κB p105 and Par6. NF-κB=nuclear factor-κB; Par6=partitioning-defective protein-6.
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