OBJECTIVE: Up to now, the mechanisms responsible for progression from noninvasive to invasive breast cancer have remained obscure. Tenascin is an extracellular matrix glycoprotein, present in embryonal and fetal tissues, which is also found in the stroma of various benign and malignant pathologies. We studied the expression and immunohistochemical behavior of tenascin in specimens of invasive and preinvasive breast cancer in order to assess its potential role as a marker for tumor invasion. MATERIALS AND METHODS: Sixty-eight specimens including 29 noninvasive ductal cancers, 12 invasive ductal cancers, 5 adenoses, 7 fibroadenomas, and 15 samples of normal human breast tissue were evaluated. An immunofluorescent microscopic technique was used for analysis of the localization and distribution of tenascin. Paraffin-embedded biopsies were incubated with primary monoclonal anti-tenascin antibodies (1:25, Dako-tenascin, TN2). Subsequently, trimethylrhodamine-isothiocyanate-conjugated secondary antibodies (rabbit anti-mouse immunglobulins (Dakopatts, Denmark) were added to visualize the protein. RESULTS: A significant tenascin expression was observed around the ducts in all samples of patients with preinvasive breast cancers. Intensive staining was also found in the periductal stroma of all specimens of patients with invasive breast cancers. Benign breast lesions showed weaker reactivity. No tenascin expression was detectable in normal human breasts, while tissue samples of in situ cancers presented variable staining intensities positively correlating with the degree of differentiation. CONCLUSION: Tenascin immunofluorescence may prove a suitable and helpful adjunct for diagnosing malignant disease and for predicting the invasive potential of premalignant breast lesions.