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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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Expression of L1CAM in NSCLC. A/B) SCC with expression of L1CAM (*) whereas the bronchial ciliated and focally metaplastic epithelium is negative (**), magnification 200x. Note on Figure 1B the pronounced expression of L1CAM in some areas of the tumor-stroma interface. C/D) Serial section, C CD31 (endothelial cells marked by arrowheads) and D L1CAM, of a SCC surrounding and partially invading the media of a blood vessel. Note that intratumoral vessels regularly show profound remodeling of the arteriolar wall with disappearance of the elastic layers normally bordering the media myocytes, magnification 200x. E) L1CAM positive tumor cells (brown) destroying the vessel wall lined by CD31 positive (red) endothelial cells. F) Accentuated L1CAM expression at the tumor-stroma interface (dashed line) and weaker (heterogeneous) L1CAM expression in the lower part of the picture representing a central part of the tumor. Hematoxylin counterstain was used for all slides.
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Figure 1: Expression of L1CAM in NSCLC. A/B) SCC with expression of L1CAM (*) whereas the bronchial ciliated and focally metaplastic epithelium is negative (**), magnification 200x. Note on Figure 1B the pronounced expression of L1CAM in some areas of the tumor-stroma interface. C/D) Serial section, C CD31 (endothelial cells marked by arrowheads) and D L1CAM, of a SCC surrounding and partially invading the media of a blood vessel. Note that intratumoral vessels regularly show profound remodeling of the arteriolar wall with disappearance of the elastic layers normally bordering the media myocytes, magnification 200x. E) L1CAM positive tumor cells (brown) destroying the vessel wall lined by CD31 positive (red) endothelial cells. F) Accentuated L1CAM expression at the tumor-stroma interface (dashed line) and weaker (heterogeneous) L1CAM expression in the lower part of the picture representing a central part of the tumor. Hematoxylin counterstain was used for all slides.

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)

Expression of L1CAM in NSCLC. A/B) SCC with expression of L1CAM (*) whereas the bronchial ciliated and focally metaplastic epithelium is negative (**), magnification 200x. Note on Figure 1B the pronounced expression of L1CAM in some areas of the tumor-stroma interface. C/D) Serial section, C CD31 (endothelial cells marked by arrowheads) and D L1CAM, of a SCC surrounding and partially invading the media of a blood vessel. Note that intratumoral vessels regularly show profound remodeling of the arteriolar wall with disappearance of the elastic layers normally bordering the media myocytes, magnification 200x. E) L1CAM positive tumor cells (brown) destroying the vessel wall lined by CD31 positive (red) endothelial cells. F) Accentuated L1CAM expression at the tumor-stroma interface (dashed line) and weaker (heterogeneous) L1CAM expression in the lower part of the picture representing a central part of the tumor. Hematoxylin counterstain was used for all slides.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198986&req=5

Figure 1: Expression of L1CAM in NSCLC. A/B) SCC with expression of L1CAM (*) whereas the bronchial ciliated and focally metaplastic epithelium is negative (**), magnification 200x. Note on Figure 1B the pronounced expression of L1CAM in some areas of the tumor-stroma interface. C/D) Serial section, C CD31 (endothelial cells marked by arrowheads) and D L1CAM, of a SCC surrounding and partially invading the media of a blood vessel. Note that intratumoral vessels regularly show profound remodeling of the arteriolar wall with disappearance of the elastic layers normally bordering the media myocytes, magnification 200x. E) L1CAM positive tumor cells (brown) destroying the vessel wall lined by CD31 positive (red) endothelial cells. F) Accentuated L1CAM expression at the tumor-stroma interface (dashed line) and weaker (heterogeneous) L1CAM expression in the lower part of the picture representing a central part of the tumor. Hematoxylin counterstain was used for all slides.
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