Abstract 5268: Differences in ERG and ANXA2 expression between Caucasian Americans and African Americans highlight distinct pathologic features of prostate cancer progression

Abstract

Abstract Introduction: Annexin A2 (ANXA2) is a Ca2+-dependent phospholipid binding protein with multiple cellular functions that include the maintenance of epithelial cell polarity. It is expressed in the luminal and basal prostate epithelium. In PIN and in moderately differentiated tumors, it is either absent or expressed focally. In contrast, a high level of ANXA2 is detected in poorly differentiated high-grade tumors. TMPRSS2:ERG gene fusion that occurs in a majority of prostate cancers results in the overexpression of ERG. We have previously reported a reciprocal correlation between ERG and ANXA2 expression in tumor specimens from a cohort 40 Caucasian American (CA) patients and showed that this is regulated through transcriptional repression of ANXA2 by ERG. This study compares the correlation of ERG and ANXA2 status in CA and African Americans (AA) to prostate cancer progression. Methods: ERG and ANXA2 expression were evaluated on whole-mounted prostate sections from 40 CA and 40 AA patients and on tissue microarrays (TMA) derived from the radical prostatectomies (RP) of 99 patients (59 CA and 40 AA) by immunochemistry. Both cohorts were matched for post RP follow-up and pathologic stage. Patients were defined as ERG- or ANXA2+ when all of the TMA cores of a given subject were ERG- or ANXA2+. Conversely, patients were defined as ERG+ or ANXA2- when any of the cores were ERG+ or ANXA-. The ERG and ANXA2 status of tumors were correlated to Gleason score and prostate cancer recurrence. Recurrence was defined as 0.2 ng/ml of serum PSA, eight weeks after RP followed by a second PSA measurement of ≥0.2 ng/ml, the initiation of radiation or hormonal therapy, or metastasis. Results: In whole mount sections, a reciprocal correlation of ERG and ANXA2 expression was noted in a majority (80%) of the CAs. However, this was observed only in 55% of AA cases. ERG+ tumors were detected in 65% of CAs as compared to 25% of AAs. In the TMAs, tumor cores from CAs are more likely to be ERG+ (46%) than those from AAs (30%). When scored by patients, CA cases were twice as likely to be ERG+/ANXA2- than ERG-/ANXA2-, while AA cases were half as likely to be ERG+/ANXA2- than ERG-/ANXA2- (p = 0.02). Intriguingly, ERG+/ANXA2- status in AAs was associated with higher pathologic stage (p = 0.03) and higher recurrence rate (p = 0.04). Conclusion: A higher frequency of ERG+/ANXA2- tumors was observed in CA men, while ERG-/ANXA2- tumors were more frequent among AA men. Surprisingly, ERG+/ANXA2- status in AAs is associated with poorer pathologic stage and prostate cancer recurrence. Taken together, our results suggest potential utility of ERG+/ANXA2- status for early identification of prostate cancer progression in AA men. Citation Format: Shyh-Han Tan, Denise Young, Yongmei Chen, Albert Dobi, Jennifer Cullen, Gyorgy Petrovics, Isabell A. Sesterhenn, Shiv Srivastava. Differences in ERG and ANXA2 expression between Caucasian Americans and African Americans highlight distinct pathologic features of prostate cancer progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5268. doi:10.1158/1538-7445.AM2015-5268