Intratumoral Blood Vessels and Basement Membranes Show Laminin β1 Overexpression in Pulmonary Squamous Cell Carcinoma and Adenocarcinoma: A Potential Target for Nanomedicine Drugs
Amanda E Lo, Alberto M Marchevsky, Mariza N de Peralta-Venturina. Cedars-Sinai Medical Center, Los Angeles, CA
Background: Laminins (LAM) are trimeric proteins that play important roles in cell adhesion to basement membranes, tumor differentiation and migration, tumor aggressivenes and angiogenesis. Vascular LAM-411 with β1 chain predicts prognosis in gliomas and other neoplasms. Cells that overexpress LAM receptor can be targeted with radioactive nanomedicine drugs in vivo for imaging and tumor suppression growth. LAM β chain expression has not been previously evaluated in normal and neoplastic lung.
Design: Twenty lung adenocarcinoma (ADC) and 20 lung squamous cell carcinomas (SCC) resection specimens were studied with immunohistochemistry (IHC) using monoclonal Laminin β1 antibody (LB1) (clone 3G133) from Abcam (Cambridge, MA) at 1:100 dilution and Laminin β2 (LB2) (clone C4) from Santa Cruz Biotechnology (Santa Cruz, CA) at 1:3K dilution. IHC was performed on 4-mm tissue sections using the Ventana Benchmark Ultra (Tuscon, AZ) using on board high pH antigen retrieval and Ventana ultraview DAB Detection Kit. Laminin β2 was also treated with Ventana Protease1 for 8 minutes. The slides were subsequently counterstained with Mayer's hematoxylin. The extent and degree of immunoreactivity in normal blood vessels (BV) and in tumoral BV and basement membrane (BM) were assessed by 2 observers and semiquantitated using a scale of 0:none, 1+:focal/weak, 2+: continuous/strong).
Results: Normal pulmonary BV larger than capillaries showed diffuse and patchy 2+ immunoreactivity for LB2 and only patchy 1+ LB1 immunoreactivity. Intraalveolar capillaries were mostly negative in all cases for both LB1 and LB2. Intratumoral BV in 95% of SCC and 55% of ADC showed 2+ LB1 immunoreactivity. In contrast, the intratumoral BV of both SCC and ADC showed LB2 immunoreactivity in only 35% of cases. Both SCC and ADC expressed 2+ LB2 BM immunoreactivity in 70% of cases. BM immunoreactivity for LB1 was seen in 55% of SCC and 10% of ADC.
Conclusions: Our results show no apparent difference in LB2 immunoreactivity between tumoral and normal pulmonary BV. In contrast, the results show an apparent upregulation of LB1 in lung carcinomas with continous strong immunoreactivity for this antigen in the neovessels of most pulmonary SCC and 55% of ADC. LB1 immunoreactivity was also detected with lower frequencies in the BM of both tumor types. These preliminary findings suggest that LB1 may offer a target for in-vivo imaging and/or suppression of tumor growth in these pulmonary neoplasms.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 297, Wednesday Afternoon