Correlated Alterations in Prostate Basal Cell Layer and Basement Membrane
AJ Liu, YG Man, WA Gardner. Beijing 301 Hospital, Beijing, China; Armed Forces Institute of Pathology and American Registry of Pathology, Washington, DC
Background: It has ben speculated that focal basal cell disruption (FBCLD) induced auto-immunoreactions represent a contributing factor for human prostate tumor progression and invasion (Man and Gardner. Med Hypoth 70: 387-408, 2008; Man and Gardner. Intern J Biol Sci 246-258,2008). Since the basement membrane surrounds and attaches to the basal cell layer, our current study assessed whether FBCLD would impact the physical integrity of the associated basement membrane.
Design: Paraffin sections from 25-human prostate tumors with both pre-invasive and invasive components were subjected to immunohistochemistry with an innovative double immunostaining protocol, to simultaneously elucidate the basal cell layer with basal cell phenotypic markers cytokeratin (CK) 34E12 and p63, and the basement membrane with corresponding markers collagen IV and laminins. The physical integrity of the basement membrane near FBCLD (defined as the absence of basal cells resulting in a gap greater than the combined size of at least three basal cells) was examined to determine the extent of correlated alterations.
Results: The frequency of FBCLD varied significantly among cases. Although most FBCLD were seen in prostatic intraepithelial neoplasia (PIN), about 30% of FBCLD were seen in hyperplastic or normal appearing ducts or acini. Of a total of 89 FBCLD detected, 76 (85 %) showed correlated alterations in the overlying basement membrane, which included distinct focal disruption or fragmentation. The basement membrane overlying the remaining 13 (15%) FBCLD showed varying degrees of attenuation or reduction of the immunostaining intensity, compared to its adjacent counterpart overlying the non-disrupted basal cell layer. Focal disruptions in both the basal cell layer and basement membrane generally occurred near morphologically distinct basal cells that lacked expression of tumor suppressor p63.
Conclusions: These findings suggest that focal disruptions in the basal cell layer and alterations in the basement membrane may be a correlated event, and that basal cells may contribute to the production of the basement membrane ((Supported by in part by grants DAMD17-01-1-0129, DAMD17-01-1-0130, PC051308 from Congressionally Directed Medical Research Programs, BCTR0706983 from The Susan G. Komen Breast Cancer Foundation to Dr. Yan-gao Man, and 2006CB910505 from the Ministry of Chinese Science and Technology Department to Drs. Xichen Zhang, Yan-gao Man, and Guiyuan Li).
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 208, Tuesday Afternoon