Laminin β1 and Laminin β2 Expression in Invasive Breast Carcinoma
Jin-Ping Lai, Xuemo Fan, Julia Ljubimova, Alexander Ljubimov, Shikha Bose. Cedars-Sinai Medical Center, Los Angeles, CA
Background: Laminins are integral components of vascular and parenchymal basement membranes and play a primary role in cell adhesion, migration and differentiation. Previous studies on fresh frozen tumor sections have demonstrated that laminin isoforms are differentially expressed in blood vessels in gliomas and breast tumors. Preclinical studies in mouse models bearing brain or breast tumors showed significant tumor growth reduction when β1 laminin chain was blocked. These data show potential in using laminins for targeted delivery of therapeutic doses of anticancer drugs. This preliminary study was designed to examine the expression of β1 and β2 laminin chains in vascular basement membranes of invasive breast cancer on formalin fixed paraffin embedded (FFPE) sections in order to validate this test for standard clinical pathology practice.
Design: Immunohistochemical staining for laminin β1 and laminin β2 chains was performed on 20 cases of FFPE breast cancers using monoclonal antibodies to laminin β1 (clone DG10) and laminin β2 (clone C4). Laminin β1 and laminin β2 staining intensities (0 to 3+) were evaluated in the intraneoplastic neovasculature and compared to that in the normal blood vessels in the surrounding parenchyma. Changes in expression were correlated to tumor characteristics including tumor size, grade, stage, ER, PR, HER2, Ki67 and p53 expression and HER2 amplification status. Statistical analysis was performed using GraphPad Prism6.
Results: Laminin β1 expression was variably increased in intraneoplastic neo-vessels in all the cases. 9 cases showed marked overexpression (2 to 3+ increase). In contrast laminin β2 expression was decreased in all the cases with 13 cases demonstrating a marked reduction (2 to 3+ decrease). A significant reverse linear correlation was noted between laminin β1 and laminin β2 expression in 13 of the cases (p=0.0008). No significant correlations were observed between the expression of laminins and tumor characteristics with the exception of PR. Breast cancers with lower levels of PR showed higher levels of laminin β1 in the intra-neoplastic new vessels (p=0.0152). High grade tumors had a higher rate (86%, 6/7) of reversal of vascular laminins from β2 to β1, although statistical significance was not reached (p=0.057).
Conclusions: Our results demonstrate a frequent switch in the expression of vascular basement membrane laminins from β2 to β1 in the neo-capillaries of invasive breast cancers. Although no prognostic significance was observed, the differential expression may be used for developing auxiliary diagnostic tests and targeted therapies.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 8, Wednesday Afternoon