[1908] Expression of Laminin β1 and β2 Chains in Malignant Mesothelioma

Amanda E Lo, Mariza N de Peralta-Venturina, Alberto M Marchevsky. Cedars-Sinai Medical Center, Los Angeles, CA

Background: Laminins (LAM) are αβγ basement membrane and extracellular matrix glycoproteins that play an important role in cell adhesion, tumor migration and metastases. LAM 411 (formerly LAM 8) β chains overexpression has been described in gliomas and other tumors but not in malignant mesothelioma (MM). LAM receptors can be blocked using antisense oligonucleotides delivered by nanobioconjugate drug, resulting in in-vivo tumor growth inhibition and there is great interest at identifying the overexpression of LAM β chains in MM and other neoplasms in an effort to develop novel LAM targeted therapeutic modalities.
Design: Twenty pleural malignant MM decortication specimens and 18 lobectomies for adenocarcinoma were studied with immunohistochemistry (IHC) using monoclonal LAM β1 antibody (clone 3G133) from Abcam (Cambridge, MA) at 1:100 dilution and LAM β2 (clone C4) from Santa Cruz Biotechnology (Santa Cruz, CA) at 1:3K dilution. Staining was evaluated in tumor cells and tumoral blood vessels (BV) in the 20 MM. Normal mesothelial cells and pleural BV were evaluated in the 18 lobectomy specimens. Extent of immunoreactivity was semi-quantitated as 0+ :<5%, 1+: 5%-25% and 2+: 26%-100%. The intensity of stainings were semi-quantitated by 2 observers from 0+: none, 1+: weak/discontinous and 2+: strong/diffuse. The proportions of staining between MM and normal pleura were compared, by compartment, using the Fishers exact test.
Results: LAM β1 and β2 are significantly overexpressed in the tumor cells of MM, with β1 staining also significant in the tumoral blood vessels compared with normal vessels.

LAM β1 and β2 Expression Distribution
 STAINING DISTRIBUTION (n)
 Negative1+2+
LAM Chainβ1β2β1β2β1β2
Tumor Cells (n=20)6541*10*14*
Mesothelial Cells (n=18)15132312
Tumor BV (n=20)1231*16*17
Normal BV (n=18)30501018
BV= blood vessels, * p<0.05



LAM β1 and β2 Expression Intensity
 STAINING INTENSITY (n)
 Negative1+2+
LAM Chainsβ1β2β1β2β1β2
Tumor Cells (n=20)6*5*539*12*
Mesothelial Cells (n=18)15132411
Tumoral BV (n=20)12*3*016*18
Normal BV (n=18)3093615
BV= blood vessels, * p<0.05


Conclusions: The overexpression of LAM β1 and β2 in tumor cells of MM and differential staining for tumoral blood vessels by β1 identify a potential therapeutic target in these neoplasms. Future studies with LAM targeted therapeutic modalities are needed to determine whether this novel approach could help improve on the currently dismal prognosis of patients with these neoplasms.
Category: Pulmonary

Wednesday, March 6, 2013 1:00 PM

Poster Session VI # 285, Wednesday Afternoon

 

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