Lysyl oxidase is involved in the main pathway of
collagen and
elastin cross-linking: it has a role in the maturation of fibrillar matrix
proteins in fibrosing processes and dictates their stability against
metalloproteases. The stromal reaction patterns in ductal
breast carcinoma are known to be morphologically varied. This has raised the hypothesis that there might be a differential expression of the
lysyl oxidase gene as a function of stromal reaction pattern. The present study investigates this potential correlation and the role of matrix
protein cross-linking in stromal differentiation.
Lysyl oxidase was detected by immunohistochemistry and
lysyl oxidase gene expression by in situ hybridization. Maximal expression was observed in myofibroblasts and myoepithelial cells around in situ
tumors and in the reactive
fibrosis facing the invasion front of infiltrating
tumors. The
lysyl oxidase substrates were observed in parallel, resulting in the stabilization of a
scar-like peritumor barrier. In contrast, a lack of
lysyl oxidase was associated with the loose or scirrhous stroma accompanying invading
tumors; here, in situ hybridization revealed
type I collagen synthesis, resulting in the deposition of non-cross-linked matrix
proteins susceptible to degradation. The early development of a cross-linked matrix around ductal
breast carcinoma suggests a possible bost defense mechanism, whereas the synchronous or late stromal reaction lacking
lysyl oxidase favors
tumor dispersion.