Differential Expression of Laminin β1 and β2 in Sinusoids and Arteries in Hepatocellular Carcinoma and Cirrhotic Liver
Stacey A Kim, Deepti Dhall, Shefali Chopra, Allen B Mendez, Melissa Kahn, Maha Guindi. Cedars-Sinai Medical Center, Los Angeles, CA
Background: Laminins are a family of vascular and epithelial basement membrane glycoproteins with various adhesive, migratory and signaling functions. Studies of gliomas have shown differential expression of β-chain isoforms as a potential therapeutic target. Capillarized sinusoids in hepatocellular carcinoma (HCC) acquire basal lamina material in the space of Disse. We studied the laminin β1 (LB1) and β2 (LB2) chain expression in sinusoidal basal lamina and arteries of HCC versus background cirrhotic liver to evaluate the staining patterns.
Design: 20 cases of HCC (with adjacent cirrhotic liver in 17) were immunohistochemically stained for LB1 and LB2. Staining intensity for sinusoids and arteries in HCC, sinusoids and hepatic artery branches and bile ducts in cirrhotic liver was recorded in a semiquantitative fashion as follows: 0=no staining, 1=weak, 2=moderate, 3=strong. Scores of 0-1 were considered overall negative, and 2-3 were considered positive. Statistical significance was analyzed with Fisher's exact test.
Results: Sinusoids in cirrhotic liver were negative for both LB1 and LB2 (0/17, 0% for both) while sinusoids in HCC showed significantly increased LB1 (14/20, 70%; p=0.0001) and LB2 (7/20, 35%; p=0.0094). LB1 and LB2 were both strong in 5 of 20 HCCs (25%). Difference between extratumoral hepatic artery branches in cirrhotic liver versus arteries in HCC was not significant for LB1 (15/17, 88% vs 18/20, 90%; p=1.000) but significant for LB2 (17/17, 100% vs 15/20, 75%; p=0.0498). Sinusoids and arteries in HCC stained more strongly for LB1 (70% and 90%) than LB2 (35% and 75%), however the difference was not significant (sinusoids, p=0.0562; arteries, p=0.4075). In contrast, extratumoral hepatic artery branches stained more strongly for LB2 (100%) than LB1 (88%) (p=0.4848). Bile ducts had low LB1 (3/17, 18%) and strong LB2 (17/17, 100%) expression.
|LB1 in sinusoids||LB2 in sinusoids|
|0/17 (0%)||14/20 (70%)||0/17 (0%)||7/20 (35%)|