Background: Annexin A2 (ANXA2) is absent or expressed focally in the prostate epithelium of moderately differentiated tumors but is highly expressed in a subset of poorly differentiated tumors. We observed earlier that ANXA2 transcription is negatively regulated by ERG in prostate cancer (CaP) cells. Here we examined whether Annexin A2 expression in prostate tumors correlates with aggressive CaP or disease progression, whether prostate tumors of Caucasian American (CA) and African American (AA) patients have distinct Annexin A2 expression profiles, and if the levels of Annexin A2 in sera is correlated to its expression in tumor tissues. We also speculated on the underlying mechanism likely to regulate ANXA2 expression in the absence of ERG.

Methods: We evaluated Annexin A2 and ERG expression in index tumors on whole-mounted prostate sections and tissue microarrays derived from radical prostatectomies of 176 patients by immunohistochemistry. Both cohorts were matched for post RP follow-up, pathologic stage, and race. ERG and Annexin A2 expression status in tumors were correlated to Gleason score, biochemical recurrence and metastasis. We measured, by enzyme-linked immunosorbent assay (ELISA), Annexin A2 proteins levels in sera of 94 controls and 222 patients, matched for race and Gleason sum. Correlation between promoter methylation and gene expression profiles of ANXA2 from TCGA studies were also examined.

Results: A significant association was found between ANXA2(+) index tumors and higher Gleason Grade Group (GG) 4 and 5, and worse pathologic stage (pT 3-4). Moreover, ERG(-)/ANXA2(+) tumors were found to be associated with Gleason GG 4 and 5, and ERG(+)/ANXA2(-) tumors with Gleason GG 1 and 2. However, unlike ERG expression, which is more prevalent in prostate tumors of CA men, Annexin A2 expression was not associated with race. Trends toward earlier occurrence of BCR and worse metastasis-free survival were observed among ANXA2(+) cases. Significantly higher levels of secreted Annexin A2 were detected in the sera healthy controls than in CaP patients. Analysis of TCGA prostate cancer dataset revealed an inverse association between methylation of the ANXA2 promoter region and ANXA2 expression in prostate tumor tissues.

Conclusion: The association between high Annexin A2 expression in prostate tumors with higher grade and stage suggests a potential for its use as a biomarker for aggressive CaP and to stratify patients after radical prostatectomy.

Citation Format: Shyh-Han Tan, Denise Young, Wei Huang, Amina Ali, Lakshmi Ravindranath, Kurt Christen, Kevin Babcock, Huai-Ching Kuo, Yongmei Chen, Jacob Kagan, Sudhir Srivastava, Albert Dobi, Srinivasan Alagarsamy, Gyorgy Petrovics, David G. McLeod, Jennifer Cullen, Inger L. Rosner, Isabell A. Sesterhenn, Shiv Srivastava. Annexin A2 expression level correlates with adverse pathology and disease progression in prostate cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C023.