LYSYL OXIDASE GENE-EXPRESSION IN THE STROMAL REACTION TO IN-SITU AND INVASIVE DUCTAL BREAST-CARCINOMA

Lysyl oxidase is involved in the main pathway of collagen and elastin cross-linking: it has a role in the maturation of fibrillar matrix pro teins in fibrosing processes and dictates their stability against meta lloproteases. The stromal reaction patterns in ductal breast carcinoma are known to be morphologically varied. This has raised the hypothesi s that there might be a differential expression of the lysyl oxidase g ene as a function of stromal reaction pattern. The present study inves tigates this potential correlation and the role of matrix protein cros s-linking in stromal differentiation. Lysyl oxidase was detected by im munohistochemistry and lysyl oxidase gene expression by in situ hybrid ization. Maximal expression was observed in myofibroblasts and myoepit helial cells around in situ turners and in the reactive fibrosis facin g the invasion front of infiltrating turners, The lysyl oxidase substr ates were observed in parallel, resulting in the stabilization of a sc ar-like peritumor barrier. In contrast, a lack of lysyl oxidase was as sociated with the loose or scirrhous stroma accompanying invading tumo rs; here, in situ hybridization revealed type I collagen synthesis, re sulting in the deposition of non-cross-linked matrix proteins suscepti ble to degradation. The early development of a cross-linked matrix aro und ductal breast carcinoma suggests a possible host defense mechanism , whereas the synchronous or late stromal reaction lacking lysyl oxida se favors tumor dispersion.