Immunohistochemical expression of AIM1 in normal prostate and in primary and metastatic prostate carcinoma
Year: 2016
Type: other
Abstract: INTRODUCTION: 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. MATERIAL & METHODS: 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. 336 tissue microarray spots were analyzed: 52 spots corresponded to lymph nodes, 138 spots to nontumor prostate, and 146 spots to prostate carcinoma. AIM1 expression was evaluated separately in the membrane and in the cytoplasm. An H-score was used to evaluate stain intensity (0-3+) and extent (0%-100%), for both membranous and cytoplasmic staining. Scores between nontumor prostate, prostate cancer, and lymph node metastasis were compared using the Kruskal-Wallis test, adjusting for tied values. Pairwise comparisons were done using the Mann-Whitney U test. 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). CONCLUSIONS: 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.
Institution: Universidad del Norte
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W2725825262