Abstract
ANXA2 (Annexin A2 or Annexin II) is a calcium dependent phospholipid binding protein with diverse cellular functions. While ANXA2 is either absent or expressed focally in the prostate epithelium of well and moderately differentiated tumours, it is highly expressed in a subset of poorly differentiated tumours. Here we examined the association between ANXA2 expression and tumour progression, with consideration of ERG expression status and patient race (Caucasian American and African American). We evaluated ANXA2 and ERG expression in index tumours by immunohistochemistry of whole mounted prostate sections and tissue microarrays derived from radical prostatectomies of 176 patients, matched for long term post-radical prostatectomy follow-up of up to 22 years (median 12.6 years), race and pathological stage. Expression of ERG and ANXA2 was analysed for correlation with grade group (GG), and pathological T (pT) stage. Kaplan-Meier estimation curves were used to examine associations between ANXA2 or ERG expression and biochemical recurrence (BCR) free survival, and distant metastasis free survival. Significant associations were found between ANXA2(+) index tumours and poorest grade groups (GG 4-5, p=0.0037), and worse pathological stage (pT 3-4, p=0.0142). Patients with ANXA2(+) prostate tumours showed trends towards earlier BCR and metastatic progression. ANXA2(+)/ERG(-) tumours were found to be associated with GG 4-5; ANXA2(-)/ERG(+) tumours, with GG 1-2 (p=0.0036). ANXA2 expression was not associated with patient race. The association between high ANXA2 expression and prostate tumours of higher grade (GG 4-5) and stage (pT 3-4) suggests a potential use for ANXA2 as a prognostic biomarker of aggressive prostate cancer.
Highlights
In the United States, prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer associated death
We evaluated ANXA2 and ERG expression by IHC in tumours of adjacent whole mounted sections (Fig. 1A–F), and in tissue microarrays (TMA) cores double stained with ANXA2 and ERG (Fig. 1G–U) from a combined study cohort of 176 patients (Table 1), to determine whether their expression in prostate tumours correlated with race (AA and CA)
ANXA2 expression was detected on the membrane, and in the cytoplasm of luminal and basal cells of benign prostate epithelium (Fig. 1B,E,H,I)
Summary
In the United States, prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer associated death. African Americans, suffer the highest incidence and mortality rates.[1] Increasing evidence suggests that biological differences in ancestry contribute to this disparity.[2,3,4] Race or ethnicity dependent dysregulated expression of prostate cancer associated genes, such as ERG, AMACR, FOXP1, GSTP1, and NKX3-1, are known to predict risk of aggressive disease.[5,6] PTEN deletion,[2,3,7] and TMPRSS2-ERG gene fusion[8,9,10,11] are more prevalent in prostate cancer of Caucasians than of Africans or Asians. Our understanding of how ERG promotes oncogenesis has prompted efforts to treat prostate cancer by targeting ERG.[12,13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
