Annexin A8 Is Up-Regulated During Mouse Mammary Gland Involution and Predicts Poor Survival in Breast Cancer

Abstract

Purpose: Microarray studies have linked Annexin A8 RNA expression to a ''basal cell^like'' subset of breast cancers, including BRCA1-related cancers, that are characterized by cytokeratin 5 (CK5) and CK17 expression and show poor prognosis. We assessed Annexin A8's contribution to the overall prognosis and its expression in normal, benign, and cancerous tissue and addressed Annexin A8's physiologic role in the mammary gland. Experimental Design: Using microarrays and reverse transcription-PCR, the Annexin A8 expression was studied during mouse mammary gland development and in isolated mammary structures. Reverse transcription-PCR on cultured human luminal and basal cells, along with immunocytochemistry on normal and benign breast tissues, was used for cellular localization. Annexin A8's prognostic relevance and its coexpression with CK5 were assessed on tissue arrays of 1,631cases of invasive breast cancer. Coexpression was further evaluated on a small cohort of 14 BRCA1-related breast cancers. Results: Annexin A8 was up-regulated during mouse mammary gland involution and in pubertal ductal epithelium. Annexin A8 showed preferred expression in cultured basal cells but predominant luminal expression in normal human breast tissue in vivo. Hyperplasias and in situ carcinomas showed a strong staining of basal cells. Annexin A8 expression was significantly associated with grade (P < 0.0001), CK5 (P < 0.0001), and estrogen receptor status (P < 0.0001); 85.7% BRCA1-related breast tumors coexpressed Annexin A8 and CK5. Conclusion: Annexin A8 is involved in mouse mammary gland involution. In humans, it is a luminally expressed protein with basal expression in cell culture and in hyperplasia/ductal carcinoma in situ. Expression in invasive breast carcinomas has a significant effect on survival (P = 0.03) but is not independent of grade or CK5.

Analysis of Integrin β4 Expression in Human Breast Cancer: Association with Basal-like Tumors and Prognostic Significance

“…This hypothesis is supported by strong evidence from the analysis of gene expression in yeast and emerging data in mammalian cells (23). The h4 signature (Table 3), as well as the h4-related gene list (Supplementary Table S1), includes known markers of basal-like breast cancers, such as K5 and K14 (38), Sox9 (19), P-cadherin (39), laminin (40), fascin (40), epidermal growth factor receptor (41), and Annexin A8 (42), and genes that are expressed primarily in basal myoepithelial cells of the mammary gland, such as WT-1 (43) and S100A2 (Table 3; Supplementary Table S1; ref. 44).…”

Aberrant expression of annexin A10 is closely related to gastric phenotype in serrated pathway to colorectal carcinoma

“…8 ANX expression has been correlated with patient survival and tumor stage. 8,12,13 Therefore, human ANXs can exhibit oncogenic and/or tumor-suppressing activities, depending on the cell context. In previous studies, we have shown that ANXA10 is a protein specifically expressed in the gastric mucosa, the Brunner gland of the duodenum and the urothelium.…”

Allelic Transcripts Dosage Effect in Morphologically Normal Ovarian Cells from Heterozygous Carriers of a BRCA1/2 French Canadian Founder Mutation

“…In humans, Annexin A8 co-expresses with CK5 and CK17 in a basal cell-like subset of human breast carcinoma with poor survival. Moreover, 85.7% of BRCA1-related breast tumors co-expressed Annexin A8 and CK5 (46). Interestingly, our results indicate a putative association of Annexin A8-like 2 with ovarian tumor progression in BRCA1 carriers.…”

“…These peptides share a common structural domain, the annexin core, which consists of 4 or more copies of annexin repeats, responsible for their calcium-regulated membrane-binding activity (46). Annexin A8 was shown to display phospholipid-and F-actin-binding properties, suggesting its involvement in the structural organization of actin-associated membrane domains (47).…”