Down-regulation of gelsolin expression in human breast ductal carcinoma insitu with and without invasion

Expression of gelsolin, an actin filament regulatory protein, in human brea st ductal carcinoma in situ (DCIS) was analyzed by immunohistochemistry usi ng a monoclonal antibody. Formalin-fixed paraffin-embedded tissues from 59 pure DCIS specimens and 33 DCIS specimens with associated invasive componen ts were evaluated for gelsolin reactivity and compared to eight normal brea st cases and 76 invasive breast cancers. The proportion of cases exhibiting negative/low expression of gelsolin in the epithelium was as follows - nor mal, 0%; pure DCIS, 56%; DCIS associated with invasion, 58% in the DCIS com ponent and 66% in the invasive component; invasive carcinoma, 70%. These da ta demonstrate that down-regulation of gelsolin expression in breast epithe lium frequently parallels progression to malignancy. Testing gelsolin expre ssion (normal vs. negative/low levels) in the DCIS lesions for associations with patient age or any of the following histopathologic parameters reveal ed no significant (95% probability level) correlations - tumor size; pathol ogic (Van Nuys system) grade; nuclear grade; necrosis; presence of histolog ic calcifications; presence or type of adjacent benign lesions; architectur al histologic pattern; and mammographic extent. Gelsolin loss was more comm only associated with mammographic soft tissue lesions as compared to calcif ied lesions (P = 0.009). A positive trend of borderline significance (P = 0 .06) found in the DCIS with invasion group was a correlation between down-r egulated gelsolin expression in the DCIS component and size (< versus great er than or equal to 15 mm) of the invasive tumor. In conclusion, reduced ge lsolin protein is detectable in at least half of breast lesions which have progressed to DCIS. The trend between increasing gelsolin loss and malignan t progression from normal epithelium to DCIS to invasive breast cancer (P < 0.0001) suggests additional investigation is needed to determine the poten tial of altered gelsolin expression as a marker for prognosis and for thera peutic interventions in breast cancer.