Immunohistochemical Expression of AIM1 in Normal Prostate and in Primary and Metastatic Prostate Carcinoma
Michael C Haffner, Srinivasan Yegnasubramanian, George J Netto, Alcides Chaux. Norte University, Asunción, Paraguay; Johns Hopkins University, Baltimore, MD
Background: Absent in melanoma 1 (AIM1) is a novel actin interacting protein that shows tumor suppressor function in prostate cancer. We have recently shown that loss of AIM1 increases actin remodeling and promotes cell invasion and cell motility in prostate epithelial cells. Herein we evaluated the expression pattern of AIM1 in normal prostate epithelium, primary prostate cancer, and lymph node metastases.
Design: To evaluate the expression pattern of AIM1in human tissues we developed a novel AIM1 specific antibody and validated its specificity. To assess the co-localization of AIM1 and actin we performed co-immunofluorescence labeling. We used immunohistochemistry to evaluate AIM1 expression in a set of 59 normal prostate tissues, 68 primary adenocarcinoma and 52 lymph node metastases. AIM1 expression was evaluated separately in the membrane and in the cytoplasm. For both, an H-score was used to evaluate stain intensity (0-3+) and extent (0%-100%).
Results: In normal prostate epithelial cells AIM1 strongly co-localized with the actin cytoskeleton resulting in a membranous staining pattern. In primary and metastatic prostate adenocarcinoma the distribution of AIM1 was dramatically altered, and AIM1 showed diffuse cytoplasmatic staining and a strongly decreased co-localization with the actin cytoskeleton. Membranous AIM1 expression was significantly higher in normal prostate epithelium compared to prostate cancer (P=0.0001). Conversely, cytoplasmic AIM1 expression was significantly higher in prostate cancer compared to normal prostate epithelium (P=0.0001). Scores for membranous and cytoplasmic AIM1 expression are summarized in Figure 1.
Conclusions: These observations suggest that redistribution of AIM1 – from a membranous staining pattern in the normal epithelium to a diffuse cytoplasmatic localization in invasive lesions – is an almost universal phenotype of prostate adenocarcinoma. It remains to be shown if this mislocalization of AIM1 is directly mechanistically linked with tumor cell invasion and metastatic dissemination.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 126, Wednesday Morning