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

YG Man MD PhD^a, T Shen MD PhD^b, YG Zhao MD PhD^c, QX Sang PhD^c

^aDepartment of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC, United States, ^bDepartment of Pathology, Temple University Medical School, Philadelphia, PA, United States, ^cDepartment of Chemistry and Biochemistry, Florida University, Tallahassee, FL, United States

AIM: 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 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 identified a subset of mammary ductal carcinoma in situ that contained focal myoepithelial (ME) cell layer disruptions, and that over 97% of these focal disruptions were immediately subjacent to leukocytes (Yousefi et al. AIMM, In press), suggesting that focal leukocyte infiltration may play direct or indirect roles in ME disruptions. As the basal cells are believed to be equivalent to the ME cells, this study attempts to assess whether a similar event occurs in prostate tumors. METHODS: Consecutive sections were prepared from 16 patients with prostate tumors containing simultaneous normal, prostatic intraepithelial neoplasia, and organ-confined carcinoma. Two immediate adjacent sections from each case were double immunostained, one for cytokeratin (CK) 34 betaE12 plus leukocyte common antigen, the other for CK 34 betaE12 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. RESULTS: Focal basal cell layer disruption was found in all 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 focally disrupted basal cell layers, while in only about 30% of the acini and ducts without basal cell layer disruptions (p <0.01). A vast majority of the proliferating (Ki-67 positive) cells were located at or near the basal cell layer disruptions. Also, clusters of multiple proliferating cells were frequently seen in acini and ducts with leukocyte infiltration, while were barely detectable in acini and ducts without focal leukocyte infiltration. CONCLUSIONS: These findings suggest that leukocytes may play direct roles in basal cell layer disruptions and tumor invasion.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 898 (Oncogenesis).