Laminin β1 and β2 Expression in Vasculature of Clear Cell Renal Cell Carcinoma
Elena E Chang, Daniel J Luthringer, Mariza dePeralta-Venturina, Nasim Babaidorabad, Alexander V Ljubimov, Julia Y Ljubimova, Mahul B Amin. Cedars-Sinai Medical Center, Los Angeles, CA
Background: Renal cell carcinomas respond to anti-angiogenic treatment modalities. Various isoforms of the basement membrane (BM) protein laminin (Ln) have been implicated in tumor angiogenesis, aggressiveness, and invasion. Recently developed Ln-targeted therapies hold promise in treatment of vascular tumors such as clear cell renal cell carcinoma (CCRCC). Greater understanding of Ln synthesis and distribution is needed, and this study investigates expression of two important subunits of Ln, β1 and β2, in BM of the CCRCC vasculature on paraffin sections.
Design: Representative sections of 20 cases of formalin-fixed paraffin embedded CCRCC were selected for immunohistochemical (IHC) staining with monoclonal antibodies for Lnβ1 (clone DG10 from Abcam (Cambridge, MA) at 1:100) and Lnβ2 (clone C4 from Santa Cruz Biotechnology (Santa Cruz, CA) at 1:3,000 dilution) chains. Positivity of Lnβ1 for tubules and Lnβ2 for glomeruli as well as vasculature within non-neoplastic kidney served as internal controls. The tumor sinusoidal vasculature and intra- and peritumoral small vessels were evaluated semiquantitatively for negative (0), weak(+1), or strong(+2) expression compared to control and focal, patchy, or diffuse distribution. These characteristics were compared with Fuhrman nuclear grade (NG).
Results: Lnβ1 and Lnβ2 were positive respectively in 95% (19/20) and 100%(20/20) of cases (1 NG1, 14 NG2, 5 NG3). Lnβ1 was variable with no identifiable pattern with respect to NG. For NG1 and NG2, Lnβ2 was +2 for all 15/15, and the majority (14/15) showed a diffuse pattern (1 patchy). For NG3, Lnβ2 expression in 4/5 was patchy (1/5 diffuse), and variable +1 to +2 intensity was noted (4/5). In 10/20 cases (1 NG1; 7 NG2, 3 NG3), slit-like small capillaries, usually at the periphery of the tumor or within the connective tissue between tumors nests were present and expressed only Lnβ1.
Conclusions: Lnβ1 and Lnβ2 synthesis and distribution appear modified in CCRCC. The sinusoidal vasculature of CCRCC is positive for both Lnβ1 and Lnβ2. Although consistently present, Lnβ1 expression was highly variable by intensity and distribution. Lnβ2 expression was consistently strong and diffuse, with decreased intensity and distribution for higher grade tumors. The significance of the small capillaries expressing only Lnβ1 remains uncertain. These changes may potentially be exploited for novel evolving targeted Ln therapies, and additional investigation is warranted.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 190, Tuesday Afternoon