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L1CAM protein expression is associated with poor prognosis in non-small cell lung cancer.

Tischler V, Pfeifer M, Hausladen S, Schirmer U, Bonde AK, Kristiansen G, Sos ML, Weder W, Moch H, Altevogt P, Soltermann A - Mol. Cancer (2011)

Bottom Line: L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05).In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown.L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. verena.tischler@usz.ch

ABSTRACT

Background: The L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT). EMT marker expression is of prognostic significance in non-small cell lung cancer (NSCLC). The relevance of L1CAM for NSCLC is unclear. We investigated the protein expression of L1CAM in a cohort of NSCLC patients. L1CAM protein expression was correlated with clinico-pathological parameters including survival and markers of epithelial-mesenchymal transition.

Results: L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05). L1CAM was an independent predictor of survival in a multivariate analysis including pT, pN, and pM category, and tumor differentiation grade. L1CAM expression positively correlated with vimentin, beta-catenin, and slug, but inversely with E-cadherin (all p-values < 0.05). E-cadherin expression was higher in the tumor center than in the tumor periphery, whereas L1CAM and vimentin were expressed at the tumor-stroma interface. In L1CAM-negative A549 cells the L1CAM expression was upregulated and matrigel invasion was increased after stimulation with TGF-beta1. In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown.

Conclusions: A subset of NSCLCs with vessel tropism and increased metastasis aberrantly expresses L1CAM. L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.

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L1CAM and EMT marker expression patterns at the tumor-stroma interface. A) SCC with expression of L1CAM at the tumor-stroma interface (brown). The tumor center shows moderate E-cadherin expression (red). At the tumor-stroma interface, E-cadherin expression is decreased. Note the strong positivity of small peripheral nerves for L1CAM. B) Double IF staining for L1CAM (green) and E-cadherin (red): L1CAM is expressed at the tumor border and E-cadherin expression is strongest in the tumor center. E-cadherin expression is decreased at the tumor border (yellow). C) Membranous E-cadherin (red) is expressed in the tumor center and decreased towards the tumor-stroma interface. Two strong Vimentin positive (brown) stromal cell aggregates are marked with dotted lines (upper left and mid to lower right). Note that most of the Vimentin positive cells show nuclear morphology of the tumor cells. CD68 staining to exclude Vimentin positive macrophages was not performed. D) Decrease of membranous E-cadherin (red) and strong nuclear expression of slug (brown) at the tumor-stroma interface of a SCC. In the tumor center E-cadherin is strongly but slug is not expressed (blue nuclei). Hematoxylin and DAPI counterstain were used, respectively. Tumor-stroma interfaces are marked by dotted lines.
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Figure 2: L1CAM and EMT marker expression patterns at the tumor-stroma interface. A) SCC with expression of L1CAM at the tumor-stroma interface (brown). The tumor center shows moderate E-cadherin expression (red). At the tumor-stroma interface, E-cadherin expression is decreased. Note the strong positivity of small peripheral nerves for L1CAM. B) Double IF staining for L1CAM (green) and E-cadherin (red): L1CAM is expressed at the tumor border and E-cadherin expression is strongest in the tumor center. E-cadherin expression is decreased at the tumor border (yellow). C) Membranous E-cadherin (red) is expressed in the tumor center and decreased towards the tumor-stroma interface. Two strong Vimentin positive (brown) stromal cell aggregates are marked with dotted lines (upper left and mid to lower right). Note that most of the Vimentin positive cells show nuclear morphology of the tumor cells. CD68 staining to exclude Vimentin positive macrophages was not performed. D) Decrease of membranous E-cadherin (red) and strong nuclear expression of slug (brown) at the tumor-stroma interface of a SCC. In the tumor center E-cadherin is strongly but slug is not expressed (blue nuclei). Hematoxylin and DAPI counterstain were used, respectively. Tumor-stroma interfaces are marked by dotted lines.

Mentions: L1CAM protein expression (any sum intensity > score 0) was found in 25% of the tumors. Similarly, 25% of the SCC and 24% of the ADCA expressed L1CAM (table 1). An overview of L1CAM expression and clinicopathological parameters is shown in table 1. Normal lung tissue, endothelial cells and bronchial epithelium were negative for L1CAM stained on whole sections (Figure 1A, B). L1CAM expression significantly correlated with the pM1 category (p = 0.031) and with blood vessel infiltration (p = 0.036; table 1). Examples of vessel infiltration and blood vessel tropism are shown in Figure 1C-E. L1CAM expression was found to be strongest at the tumor-stroma interface (Figure 1B, F and 2A, B). Expression of L1CAM was found to be heterogeneous in 63/468 (13.5%) of cases which was confirmed in randomly selected cases by whole sections (Figure 1F).


L1CAM protein expression is associated with poor prognosis in non-small cell lung cancer.

Tischler V, Pfeifer M, Hausladen S, Schirmer U, Bonde AK, Kristiansen G, Sos ML, Weder W, Moch H, Altevogt P, Soltermann A - Mol. Cancer (2011)

L1CAM and EMT marker expression patterns at the tumor-stroma interface. A) SCC with expression of L1CAM at the tumor-stroma interface (brown). The tumor center shows moderate E-cadherin expression (red). At the tumor-stroma interface, E-cadherin expression is decreased. Note the strong positivity of small peripheral nerves for L1CAM. B) Double IF staining for L1CAM (green) and E-cadherin (red): L1CAM is expressed at the tumor border and E-cadherin expression is strongest in the tumor center. E-cadherin expression is decreased at the tumor border (yellow). C) Membranous E-cadherin (red) is expressed in the tumor center and decreased towards the tumor-stroma interface. Two strong Vimentin positive (brown) stromal cell aggregates are marked with dotted lines (upper left and mid to lower right). Note that most of the Vimentin positive cells show nuclear morphology of the tumor cells. CD68 staining to exclude Vimentin positive macrophages was not performed. D) Decrease of membranous E-cadherin (red) and strong nuclear expression of slug (brown) at the tumor-stroma interface of a SCC. In the tumor center E-cadherin is strongly but slug is not expressed (blue nuclei). Hematoxylin and DAPI counterstain were used, respectively. Tumor-stroma interfaces are marked by dotted lines.
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Figure 2: L1CAM and EMT marker expression patterns at the tumor-stroma interface. A) SCC with expression of L1CAM at the tumor-stroma interface (brown). The tumor center shows moderate E-cadherin expression (red). At the tumor-stroma interface, E-cadherin expression is decreased. Note the strong positivity of small peripheral nerves for L1CAM. B) Double IF staining for L1CAM (green) and E-cadherin (red): L1CAM is expressed at the tumor border and E-cadherin expression is strongest in the tumor center. E-cadherin expression is decreased at the tumor border (yellow). C) Membranous E-cadherin (red) is expressed in the tumor center and decreased towards the tumor-stroma interface. Two strong Vimentin positive (brown) stromal cell aggregates are marked with dotted lines (upper left and mid to lower right). Note that most of the Vimentin positive cells show nuclear morphology of the tumor cells. CD68 staining to exclude Vimentin positive macrophages was not performed. D) Decrease of membranous E-cadherin (red) and strong nuclear expression of slug (brown) at the tumor-stroma interface of a SCC. In the tumor center E-cadherin is strongly but slug is not expressed (blue nuclei). Hematoxylin and DAPI counterstain were used, respectively. Tumor-stroma interfaces are marked by dotted lines.
Mentions: L1CAM protein expression (any sum intensity > score 0) was found in 25% of the tumors. Similarly, 25% of the SCC and 24% of the ADCA expressed L1CAM (table 1). An overview of L1CAM expression and clinicopathological parameters is shown in table 1. Normal lung tissue, endothelial cells and bronchial epithelium were negative for L1CAM stained on whole sections (Figure 1A, B). L1CAM expression significantly correlated with the pM1 category (p = 0.031) and with blood vessel infiltration (p = 0.036; table 1). Examples of vessel infiltration and blood vessel tropism are shown in Figure 1C-E. L1CAM expression was found to be strongest at the tumor-stroma interface (Figure 1B, F and 2A, B). Expression of L1CAM was found to be heterogeneous in 63/468 (13.5%) of cases which was confirmed in randomly selected cases by whole sections (Figure 1F).

Bottom Line: L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05).In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown.L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. verena.tischler@usz.ch

ABSTRACT

Background: The L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT). EMT marker expression is of prognostic significance in non-small cell lung cancer (NSCLC). The relevance of L1CAM for NSCLC is unclear. We investigated the protein expression of L1CAM in a cohort of NSCLC patients. L1CAM protein expression was correlated with clinico-pathological parameters including survival and markers of epithelial-mesenchymal transition.

Results: L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05). L1CAM was an independent predictor of survival in a multivariate analysis including pT, pN, and pM category, and tumor differentiation grade. L1CAM expression positively correlated with vimentin, beta-catenin, and slug, but inversely with E-cadherin (all p-values < 0.05). E-cadherin expression was higher in the tumor center than in the tumor periphery, whereas L1CAM and vimentin were expressed at the tumor-stroma interface. In L1CAM-negative A549 cells the L1CAM expression was upregulated and matrigel invasion was increased after stimulation with TGF-beta1. In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown.

Conclusions: A subset of NSCLCs with vessel tropism and increased metastasis aberrantly expresses L1CAM. L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.

Show MeSH
Related in: MedlinePlus