Decreased Expression Levels of Phosphorylated Ser239-Vasodilator-Stimulated Phosphoprotein Indicate Progression from In-Situ to Invasive Breast Carcinomas
Paolo Cotzia, Alessandro Bombonati, Mehboob Ali, Juan P Palazzo, Ruth Birbe, Giovanni Pitari. Thomas Jefferson University Hospital, Philadelphia, PA
Background: Vasodilator-stimulated phosphoprotein (VASP) is an actin-binding protein promoting actin polymerization, dynamic membrane regions and epithelial cell barrier function. VASP activity is precisely regulated through Ser phosphorylation. Recent studies have shown that changes in VASP expression modulate adhesion and proliferation of breast cancer cells.
Design: To examine the relationship between VASP Ser phosphorylation and the carcinogenic process, VASP and its Ser phosphorylated forms (pSer157-VASP and pSer239-VASP) were examined by immunohistochemistry in paraffin-embedded specimens, assembled into 2 tissue micro-arrays (TMA) with each patient represented by duplicate samples. Human tissues were obtained from the tumor bank of the Department of Pathology, Anatomy and Cell Biology at Thomas Jefferson University Hospital, under a protocol approved by the Institutional Review Board. One TMA contained 24 ductal carcinoma in-situ (DCIS): 9 grade I-II and 15 grade III. The second TMA had 69 invasive ductal carcinomas (IDC): 14 grade I and 55 grade II. Specific membranous and/or cytoplasmic staining was scored semiquantitatively (0-to-3 scale: 0, absent; 1+, weak in less than 10% of cancer cells; 2+, moderate in 10-30%; 3+, moderate and/or strong in more than 30%).
Results: Expression of all 3 VASP biomarkers was significantly decreased in IDC, compared to DCIS. Of note, pSer239-VASP was the most compromised biomarker and represented an independent diagnostic discriminator of non-invasive versus invasive disease. In DCIS, pSer239-VASP expression was significantly decreased in grade III compared to grades I-II. Further, in IDC grade II tumors exhibited significantly lower levels of pSer239-VASP than those of grade I.
Conclusions: - Decreased expression of VASP biomarkers is associated with the progression from in-situ to invasive ductal carcinoma of the breast.
- pSer239-VASP is a novel predictor of breast stromal invasion, which could be used as an immunohistochemical tool to identify those DCIS with high potential to progress to invasive disease.
Monday, March 4, 2013 1:00 PM
Poster Session II # 62, Monday Afternoon