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

Abstract

Vimentin, nuclear factor-kB (NF-kB) p105, fascin, E-cadherin, TGF-b, 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-kB p105 (P ¼ 0.02) and E-cadherin (P ¼ 0.03) were positive prognostic indicators for disease-specific survival (DSS), whereas high tumour epithelial cell expression of vimentin (P ¼ 0.001) was a negative prognostic indicator. High expression of NF-kB p105 (P ¼ 0.001) and Par6 (P ¼ 0.0001) in the stromal compartment correlated with a good prognosis. In multivariate analyses, the tumour epithelial cell expression of NF-kB p105 (P ¼ 0.0001) and vimentin (P ¼ 0.005) and the stromal cell expression of NF-kB p105 (P ¼ 0.007) and Par6 (P ¼ 0.0001) were independent prognostic factors for DSS. High expression of NF-kB 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-kB p105 and Par6 are both favourable independent prognostic indicators.

Vimentin expression is associated with decreased survival in gastric cancer

“…Vimentin has been observed in both stromal cells and cancer cells in breast, lung, and oral cancer (3,(10)(11)(12). Liu et al reported that immunoreactivity of vimentin in cancer cells was associated with tumor progression and worse survival in patients with oral squamous cell carcinomas (12).…”

“…In other studies, vimentin was detected in both the parenchyma and mesenchyma of various types of cancers, including breast cancer, non-small cell lung cancer, and oral squamous cell carcinoma (7)(8)(9)(10)(11)(12). Vimentin expression in cancer epithelial cells has been associated with metastasis and poor survival (10,12). In gastric cancer, the prognostic value of vimentin remains unclear.…”

Stromal CD8+ T-cell Density—A Promising Supplement to TNM Staging in Non–Small Cell Lung Cancer

“…Although our group has studied more than 100 prognostic markers related to in situ tumor immunology (11,13,14,17,18), angiogenesis (19)(20)(21), and epithelial-mesenchymal transition (22) in NSCLC, stromal CD8 þ score (CD8 þ TIL density in the tumor-related stroma) has been one of the markers with the strongest prognostic impact independent of other clinicopathologic variables including TNM classification. Furthermore, cytotoxic CD8 þ T cells are of increasing interest in lung cancer as novel targeted therapies are aiming to stimulate the immune defense by blocking mechanisms that may inhibit cytotoxic T lymphocytes, e.g., programmed death-1 (PD1), PD-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4; ref.…”

Potential Anti-metastasis Natural Compounds for Lung Cancer

“…EMT was also shown to increase cell invasive ability by triggering matrix metalloproteinases (MMPs), such as MMP-2, MMP-3 and MMP-9 (50). In NSCLC, the low vimentin level was found to be a predictor of better survival in primary NSCLC (51). EMT phenotypes in primary cells of lung cancer have been shown to link with anoikis and chemotherapeutic resistance (52,53).…”