Survival analysis between patients with invasive ductal and invasive lobular breast cancer.

OBJECTIVE: Differences in overall survival (OS) and disease-free survival (DFS) between patients with invasive ductal (IDC) and invasive lobular breast cancer (ILC) are controversial. STUDY DESIGN: The study population was selected from a database of 5,689 female patients with invasive breast cancer. In order to focus on the impact of tumour histology, all primary metastatic patients and patients with adjuvant chemotherapy or anti-hormonal treatment were excluded. Only patients with pure invasive lobular and invasive ductal histology were included. RESULTS: Multivariate survival analyses of 2,058 eligible patients confirmed tumour histology as an independent prognostic factor for OS in invasive breast cancer (p = 0.046) but not for DFS (p = 0.599). Kaplan-Meier survival analysis of OS between IDC and ILC patients showed a statistically significantly better OS for patients with ILC (p = 0.0302). DFS was not statistically different (p = 0.6659) between IDC and ILC. Univariate survival analyses of tumour size, tumour grading and nodal status in our study population were highly statistically significant for OS and DFS (p < 0.0000). CONCLUSION: Patients in our study population with ILC have significantly better OS than patients with IDC. Differences in DFS are not statistically significant.

ADAM15 decreases integrin alphavbeta3/vitronectin-mediated ovarian cancer cell adhesion and motility in an RGD-dependent fashion.

We have recently described that integrin alphavbeta3 upon interaction with its major extracellular matrix ligand vitronectin induces adhesion, motility, and proliferation of human ovarian cancer cells. Due to the important function of alphavbeta3 in cancer cell biology, it has been the effort of many scientific approaches to specifically target alphavbeta3-mediated cell adhesion and tumorbiological effects arising thereof by synthetic integrin antagonists. More recently, proteins of the ADAM family have been recognized as naturally occurring integrin ligands. Among those, human ADAM15 which encompasses the integrin binding RGD motif was shown to interact with integrin alphavbeta3. Thus, we investigated in human ovarian OV-MZ-6 cancer cells, expressing both ADAM15 and alphavbeta3, whether ADAM15 might affect alphavbeta3-mediated tumorbiological effects. We stably (over)expressed ADAM15 or its extracellular domain in OV-MZ-6 cells as well as respective ADAM15 mutants containing the tripeptide SGA instead of RGD. Cells (over)expressing ADAM15-RGD exhibited a significantly reduced alphavbeta3-mediated adhesion to vitronectin. Also, a significant time-dependent decline in numbers of cells cultivated on vitronectin was noticed. This effect was found to be rather due to impaired alphavbeta3-mediated cell adhesion than decreased cell proliferation rates, since de novo DNA synthesis was not significantly altered by elevated ADAM15 expression. Moreover, a substantially decreased random cellular motility was noticed as a function of ADAM15 encompassing an intact RGD motif. In conclusion, our results point to a physiological role of ADAM15 as a natural binding partner of integrin alphavbeta3 thereby loosening tumor cell adhesion to the underlying matrix and regulating tumor cell migration and invasion.