Carcinoma ex-pleomorphic adenoma (CXPA) is an aggressive salivary gland malignancy, usually derived from a long-standing or a recurrent benign tumor, the pleomorphic adenoma (PA). In the context of dynamic reciprocity, changes in the composition and structure of extracellular matrix proteins and cell surface receptors have been frequently associated with dysfunctional adhesion and invasive behavior of tumor cells. It is not fully understood if these changes are involved in the conversion of PA to CXPA. In this study, different progression stages of CXPA were investigated regarding the expression of the major extracellular matrix proteins, collagen type I, and of E-cadherin and β-catenin, the components of adherens junctions. By immunohistochemical analysis, we have demonstrated that direct contact of tumor cells with fibrillar type I collagen, particularly near the invasive front and in invasive areas prevailing small nests of CXPA cells, could be associated with reduced expression of the E-cadherin and β-catenin adhesion molecules and with invasive behavior of epithelial, but not of CXPA with myoepithelial component. Our results also suggested that this association could depend on the organization of collagen molecules, being prevented by high-order polymeric structures. These findings could implicate the local microenvironment in the transition from the premalignant PA to invasive CXPA.
*Department of Oral Pathology, São Leopoldo Mandic Research Center, Campinas
Departments of ‡Pathology
§Oral Pathology, University of São Paulo
†Department of Pathology, State University of Campinas, Campinas, São Paulo, Brazil
Supported by the Brazilian Agencies FAPESP and CNPq.
Reprints: Ana Paula Dias Demasi, PhD, Departamento de Patologia Oral, Faculdade de Odontologia e Centro de Pesquisas São Leopoldo Mandic, Rua José Rocha Junqueira, 13, CEP 13045-610, Campinas, São Paulo, Brazil (e-mail: firstname.lastname@example.org).
Received for publication August 4, 2008; accepted November 8, 2008