Focal prostate basal cell layer disruptions and leukocyte infiltration are correlated events: Implications for tumor invasion

1775 The normal human prostate epithelium is physically separated from the stroma by both the basal cell layer and basement membrane. Due to this structural feature, the disruption of both the basal cell layer and basement membrane is an absolute pre-requisite for tumor invasion and metastasis. The disruption of the basement membrane is believed to result from an elevated production of proteolytic enzymes by the tumor and/or stromal cells, while the mechanism for basal cell layer disruptions is elusive. In a previous study, we found that a subset of mammary ductal carcinoma in situ contained focal disruptions in their myoepithelial (ME) cell layers, and that over 97% of these ME disruptions were subjacent to leukocytes (Yousefi et al. AIMM, in press). As the basal cell layer is believed to be equivalent to the ME cell layer, this study attempts to assess whether a similar event occurs in pre-invasive prostate tumors. Consecutive sections were prepared from prostate tumors containing simultaneous normal, prostatic intraepithelial neoplasia, and organ-confined carcinoma. Two immediate adjacent sections from each of 16 selected cases were double immunostained, one for cytokeratin (CK) 34betaE12 plus leukocyte common antigen, the other for CK 34betaE12 plus Ki-67. Acini and ducts lined by over 40 epithelial cells were examined for a focal basal layer disruption, defined as the absence of basal cells resulting in a gap equal to or greater than the combined size of 3 basal or epithelial cells. Focal basal cell layer disruption was found in all the cases, while the frequency among cases varied from less than 5% to over 15% of the acini and ducts examined. Focal leukocyte infiltration was seen in over 90% of the acini and ducts with focal basal cell layer disruptions, while in only about 30% of the acini and ducts without focal basal cell layer disruptions (p