Differential Expression of Laminin β1 and β2 Isoforms in Pancreatic Adenocarcinoma
Allen B Mendez, Stacey A Kim, Maha Guindi, Melissa Kahn, Shefali Chopra, Alexander V Ljubimov, Julia Y Ljubimova, Deepti Dhall. Cedars-Sinai Medical Center, Los Angeles, CA
Background: Laminins are a family of heterotrimeric glycoproteins that are integral components of vascular and parenchymal basement membranes and are involved in adhesive, signaling, and migratory functions. Vascular β chain isoforms are differentially expressed in gliomas and breast tumors (β1>β2), involved in tumor angiogenesis and invasion. Therapeutic targeting of laminin expression with antisense oligonucleotides resulted in tumor inhibition in a mouse model. This preliminary study has been performed to define the expression profile of laminin β1 (LB1) and laminin β2 (LB2) isoforms in capillaries and glands of pancreatic adenocarcinomas versus normal pancreas in order to determine if novel therapeutic laminin targeting drugs might be efficacious in treatment.
Design: 16 cases of formalin fixed paraffin embedded pancreatic adenocarcinoma (9 with adjacent normal pancreatic tissue) were immunohistochemically stained for LB1 and LB2. The predominant pattern of staining intensity was then evaluated in the capillaries and glands within the tumor and in adjacent pancreatic parenchyma in a semiquantitative fashion as follows: 0=no staining, 1=weak, 2=moderate, or 3=strong. The negative staining and positive staining was defined as 0-1 and 2-3, respectively.
Results: Extratumoral capillaries were positive for LB1 and LB2 (both; 9/9 = 100%), whereas intratumoral capillaries showed increased (p = 0.0021) staining for LB1 (15/16 = 88%) compared with LB2 (6/16 = 37.5%). The decreased LB2 in intratumoral capillaries was also significant (p = 0.0028) compared with extratumoral capillary staining. Extratumoral pancreatic ducts did not show any differential β isoform expression (β1 5/9 = 56%; β2 6/9 = 67%). Tumor basement membranes showed stable expression of LB1 (8/16 = 50%) and a loss of LB2 (3/16 = 19%) that was significant (p=0.031) when compared to normal. There was no significant relationship between the presence of lymph node metastases (11/16 = 69%) or tumor grade (high grade = 7; low grade = 8) and tumoral capillary or duct expression of LB1 and LB2.
Conclusions: Significantly less LB2 staining was observed in intratumoral vasculature when compared with LB1 staining as well as with extratumoral vessels. There was also significantly less LB2 staining in malignant ducts when compared with extratumoral ducts. This study provides novel data on tumor basement membrane remodeling in pancreatic adenocarcinoma, which could be useful for future diagnostic and/or therapeutic decision making.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 169, Tuesday Afternoon