Altered expression and localization of PKC eta in human breast tumors

Protein kinase C (PKC) eta is a PKC isoform whose upregulation is associate d with differentiation in many epithelial tissues, including the rat mammar y gland. The purpose of this study was to examine whether PKC eta is altere d, in expression or localization, in human breast cancer. Paraffin sections of 49 in situ breast lesions, 29 invasive breast tumors, and nine normal b reast biopsies were examined for PKC eta expression by immunohisto chemistr y. Adjacent regions of normal epithelium, and in situ lesions that were pre sent adjacent to invasive lesions were also analyzed. In normal epithelium, regardlessof the presence of adjacent in situ or invasive lesions, PKC eta was present in the cytoplasm of the luminal epithelium, and increased inar eas of normal lobular development, similar to normal rat mammary gland. PKC eta staining intensity was homogeneous in normal lobules, but heterogeneou s in in situ and invasive lesions, being focally increased in cells with ab errant nuclear morphology. In situ lesions were similar to adjacent normal epithelium in average staining intensity, regardless of whether invasion wa s also present. However, the invasive lesions themselves were significantly decreased in staining intensity compared to adjacent in situ lesions. In a ddition, 75% of invasive breast cancer lesions showed decreased staining re lative to adjacent normal epithelium, compared to 37% of in situ lesions. T he invasive tumors which possessed high PKC eta staining were associated wi th positive lymph node status. These results demonstrate that quantitative and qualitative alterations in PKC eta occur in human breast cancers.