Expression of Annexin A3 in cancer

Abstract Annexin A3 (ANXA3) is a member of the annexin family of calcium-dependent phospholipid-binding proteins and plays a major role in various membrane-related processes. ANXA3 expression was analyzed by immunohistochemistry (IHC) on tissue microarrays (TMAs) containing 17,285 samples from 148 different tumor types. ANXA3 staining was seen in 10,223 (75.9%) of the 13,472 interpretable tumors and was considered weak in 16.3%, moderate in 10.1%, and strong in 49.4% of cases. Of 148 tumor categories, 128 showed ANXA3 expression in at least one case, and 110 included at least one case with strong staining. High ANXA3 expression was linked to high grade ( p < 0.0001), muscle invasive growth (pTa vs. pT2-4; p < 0.0001) and high pT-stage ( p = 0.0267) in urothelial carcinoma; lymphatic invasion ( p = 0.0307) in colorectal adenocarcinoma; high pT-stage ( p = 0.0211) in gastric adenocarcinoma; high pT-stage ( p < 0.0001), nodal positivity ( p = 0.0004) and high grade ( p < 0.0001) in hepatocellular carcinoma; and high pT-stage ( p = 0.0410) in papillary thyroid carcinoma. Low ANXA3 expression was linked with lymphatic invasion ( p < 0.0001) in urothelial carcinoma, high tumor grade in invasive breast carcinoma of no special type ( p < 0.0001); high UICC- ( p = 0.0008) and pT-stage ( p < 0.0001) in clear cell renal cell carcinoma; high ISUP grade ( p = 0.0135), high UICC- ( p = 0.0073) and pT-stage ( p = 0.0003) in papillary renal cell carcinoma; advanced pT-stage ( p = 0.0464) in pancreatic ductal adenocarcinoma; high pT-stage ( p = 0.0056) and mismatch repair deficiency ( p < 0.0001) in colorectal adenocarcinoma; and high pT-stage ( p = 0.0427) in endometrioid endometrial carcinoma. It is concluded, that ANXA3 is abundantly expressed across a broad spectrum of cancer entities and that it exerts a tissue-dependent oncogenic or tumor-suppressive role.