Advertisement

Breast Cancer Research and Treatment

, Volume 174, Issue 1, pp 113–120 | Cite as

ANXA2 expression in African American triple-negative breast cancer patients

  • Lee D. GibbsEmail author
  • Pankaj Chaudhary
  • Kelsey Mansheim
  • Richard J. Hare
  • Rebecca A. Mantsch
  • Jamboor K. Vishwanatha
Preclinical study
  • 126 Downloads

Abstract

Purpose

Our aim was to determine the role of Annexin A2 (AnxA2), which we have previously found to contribute to the aggressiveness of TNBC, with AA TNBC patients and clinical outcome.

Methods

We analyzed TCGA breast cancer database (n = 1098) to observe AnxA2 expression within breast cancer subtypes and is correlation with overall survival. Further, we examined breast tissue specimens (n = 119) through chromogenic in situ hybridization (CISH) and specimen were scored independently by two pathologists in a blinded study.

Results

In our TCGA analysis, high expression of AnxA2 was correlated with poor survival in patients with TNBC. AnxA2 gene expression was not correlated with poor survival in other breast cancer subtypes. AnxA2 average CISH intensity score (CISH score = 0, null expression to 3, high expression) for TNBC was significantly higher in comparison to estrogen receptor and/or progesterone receptor positive, human epidermal growth factor positive, and non-malignant tissues. Furthermore, AnxA2 average score was significantly higher in AA TNBC patients (CISH average score = 2.45 ± 0.3266) in comparison to Caucasian TNBC patients (CISH average score = 1.1 ± 0.4069).

Conclusion

AnxA2 is overexpressed in TNBC, implicating AnxA2 as a contributor to the aggressive biology of TNBC in AA women.

Keywords

Triple-negative breast cancer African American Annexin A2 Prognosis Biomarker 

Notes

Author contributions

LDG, PC and JKV conceived and designed the experiments. LDG, KM, RJH, RAM, and JKV performed the research and analyzed the data. LDG, PC, and JKV interpreted the data. LDG, PC, and JKV contributed to IRB approval and procurement of breast tissues. LDG wrote the paper. All authors read and approved the final manuscript.

Funding

Research reported in this publication was supported by of the National Institutes of Health under the National Cancer Institute Award Number R01CA220273 and National Institute on Minority Health and Health Disparities Award Number P20MD006882. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10549_2018_5030_MOESM1_ESM.jpg (4.8 mb)
Supplemental Figure S1 (JPG 4,935 KB) Positive and Negative Controls for chromogenic in situ hybridization. CISH Scramble (top panel), Beta-Actin (middle panel), and H&E (bottom panel) staining of TMA aggressive cancer tumor sections.

References

  1. 1.
    American Cancer Society (n.d.) How common is breast cancer? American Cancer Society. N.p. 12 Mar 2017Google Scholar
  2. 2.
    Jemal A et al (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90CrossRefGoogle Scholar
  3. 3.
    Schneider B et al (2008) Triple-negative breast cancer: risk factors to potential targets. Clin Cancer Res 14(24):8010–8018CrossRefGoogle Scholar
  4. 4.
    Albain K et al (2009) Racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group. J Natl Cancer Inst 101:984CrossRefGoogle Scholar
  5. 5.
    Rakha EA, Chan S (2011) Metastatic triple-negative breast cancer. Clin Oncol 23(9):587–600CrossRefGoogle Scholar
  6. 6.
    Bauer KR et al (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype. Cancer 109(9):1721–1728CrossRefGoogle Scholar
  7. 7.
    Irshad S, Ellis P, Tutt A (2011) Molecular heterogeneity of triple-negative breast cancer and its clinical implications. Curr Opin Oncol 23(6):566–577CrossRefGoogle Scholar
  8. 8.
    Metzger-Filho O et al (2012) Dissecting the heterogeneity of triple-negative breast cancer. J Clin Oncol 30(15):1879–1887CrossRefGoogle Scholar
  9. 9.
    Millis SZ et al (2015) Predictive biomarker profiling of> 6000 breast cancer patients shows heterogeneity in TNBC, with treatment implications. Clin Breast Cancer 15(6):473–481CrossRefGoogle Scholar
  10. 10.
    Bareche Y et al (2018) Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis. Ann Oncol 29:895–902CrossRefGoogle Scholar
  11. 11.
    de Graauw M et al (2008) Annexin A2 phosphorylation mediates cell scattering and branching morphogenesis via cofilin activation. Mol Cell Biol 28(3):1029–1040CrossRefGoogle Scholar
  12. 12.
    Gerke V, Creutz CE, Moss SE (2005) Annexins: linking Ca2+ signalling to membrane dynamics. Nat Rev Mol Cell Biol 6(6):449–461CrossRefGoogle Scholar
  13. 13.
    Grieve AG, Moss SE, Hayes MJ (2012) Annexin A2 at the interface of actin and membrane dynamics: a focus on its roles in endocytosis and cell polarization. Int J Cell Biol.  https://doi.org/10.1155/2012/852430 Google Scholar
  14. 14.
    Valapala M, Vishwanatha JK (2011) Lipid raft endocytosis and exosomal transport facilitate extracellular trafficking of annexin A2. J Biol Chem 286(35):30911–30925CrossRefGoogle Scholar
  15. 15.
    Kpetemey M et al (2015) MIEN1, a novel interactor of Annexin A2, promotes tumor cell migration by enhancing AnxA2 cell surface expression. Mol Cancer 14(1):156CrossRefGoogle Scholar
  16. 16.
    Chuthapisith S et al (2009) Annexins in human breast cancer: possible predictors of pathological response to neoadjuvant chemotherapy. Eur J Cancer 45(7):1274–1281CrossRefGoogle Scholar
  17. 17.
    Bharadwaj A, Bydoun M, Holloway R, Waisman D (2013) Annexin A2 heterotetramer: structure and function. Int J Mol Sci 14(3):6259–6305CrossRefGoogle Scholar
  18. 18.
    Lokman NA, Ween MP, Oehler MK, Ricciardelli C (2011) The role of annexin A2 in tumorigenesis and cancer progression. Cancer Microenviron 4(2):199–208CrossRefGoogle Scholar
  19. 19.
    Jeon YR et al (2013) Identification of annexin II as a novel secretory biomarker for breast cancer. Proteomics 13(21):3145–3156CrossRefGoogle Scholar
  20. 20.
    Sharma MR et al (2006) Angiogenesis-associated protein annexin II in breast cancer: selective expression in invasive breast cancer and contribution to tumor invasion and progression. Exp Mol Pathol 81(2):146–156CrossRefGoogle Scholar
  21. 21.
    Chaudhary P, Thamake SI, Shetty P, Vishwanatha JK (2014) Inhibition of triple-negative and Herceptin-resistant breast cancer cell proliferation and migration by Annexin A2 antibodies. Br J Cancer 111(12):2328–2341CrossRefGoogle Scholar
  22. 22.
    Wang CY, Lin CF (2014) Annexin A2: its molecular regulation and cellular expression in cancer development. Disease Markers.  https://doi.org/10.1155/2014/308976 Google Scholar
  23. 23.
    Shetty PK et al (2012) Reciprocal regulation of annexin A2 and EGFR with Her-2 in Her-2 negative and herceptin-resistant breast cancer. PLoS ONE 7(9):e44299CrossRefGoogle Scholar
  24. 24.
    Cancer Genome Atlas Network (2012) Comprehensive molecular portraits of human breast tumors. Nature 490(7418):61.CrossRefGoogle Scholar
  25. 25.
    Gibbs LD, Vishwanatha JK (2018) Prognostic impact of AnxA1 and AnxA2 gene expression in triple-negative breast cancer. Oncotarget 9(2):2697CrossRefGoogle Scholar
  26. 26.
    Zhu Y, Qiu P, Ji Y (2014) TCGA-assembler: open-source software for retrieving and processing TCGA data. Nat Methods 11(6):599CrossRefGoogle Scholar
  27. 27.
    Madrid MA, Lo RW (2004) Chromogenic in situ hybridization (CISH): a novel alternative in screening archival breast cancer tissue samples for HER-2/neu status. Breast Cancer Res 6(5):R593CrossRefGoogle Scholar
  28. 28.
    Hudis CA, Gianni L (2011) Triple-negative breast cancer: an unmet medical need. Oncologist 16(Supplement 1):1–11CrossRefGoogle Scholar
  29. 29.
    Mavaddat N et al (2012) Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Prev Biomark 21(1):134–147CrossRefGoogle Scholar
  30. 30.
    Nanda R, Schumm LP, Cummings S, Fackenthal JD, Sveen L, Ademuyiwa F, Cobleigh M et al (2005) Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry. JAMA 294(15):1925–1933CrossRefGoogle Scholar
  31. 31.
    Chlebowski RT et al (2005) Ethnicity and breast cancer: factors influencing differences in incidence and outcome. J Natl Cancer Inst 97(6):439–448CrossRefGoogle Scholar
  32. 32.
    Kanaan YM et al (2014) Metabolic profile of triple-negative breast cancer in African-American women reveals potential biomarkers of aggressive disease. Cancer Genomics-Proteomics 11(6):279–294Google Scholar
  33. 33.
    Sturtz LA et al (2014) Outcome disparities in African American women with triple negative breast cancer: a comparison of epidemiological and molecular factors between African American and Caucasian women with triple negative breast cancer. BMC Cancer 14(1):62CrossRefGoogle Scholar
  34. 34.
    Dietze EC et al (2015) Triple-negative breast cancer in African-American women: disparities versus biology. Nat Rev Cancer 15(4):248–254CrossRefGoogle Scholar
  35. 35.
    Sørlie T et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci 98(19):10869–10874CrossRefGoogle Scholar
  36. 36.
    Sørlie T et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci 100(14):8418–8423CrossRefGoogle Scholar
  37. 37.
    Robinson TJW et al (2013) RB1 status in triple negative breast cancer cells dictates response to radiation treatment and selective therapeutic drugs. PLoS ONE 8(11):e78641CrossRefGoogle Scholar
  38. 38.
    Gordon V, Banerji S (2013) Molecular pathways: PI3K pathway targets in triple-negative breast cancers. Clin Cancer Res 19(14):3738–3744CrossRefGoogle Scholar
  39. 39.
    Witkiewicz AK et al (2012) RB-pathway disruption is associated with improved response to neoadjuvant chemotherapy in breast cancer. Clin Cancer Res 18(18):5110–5122CrossRefGoogle Scholar
  40. 40.
    Jiang Z et al (2011) RB1 and p53 at the crossroad of EMT and triple-negative breast cancer. Cell Cycle 10(10):1563–1570CrossRefGoogle Scholar
  41. 41.
    Prat A et al (2013) Molecular characterization of basal-like and non-basal-like triple-negative breast cancer. Oncologist 18(2):123–133CrossRefGoogle Scholar
  42. 42.
    Lindner R et al (2013) Molecular phenotypes in triple negative breast cancer from African American patients suggest targets for therapy. PloS ONE 8(11):e71915CrossRefGoogle Scholar
  43. 43.
    Maji S, Chaudhary P, Akopova I, Nguyen PM, Hare RJ, Gryczynski I, Vishwanatha JK (2017) Exosomal annexin II promotes angiogenesis and breast cancer metastasis. Mol Cancer Res 15(1):93–105CrossRefGoogle Scholar
  44. 44.
    Spratt DE et al (2016) Racial/ethnic disparities in genomic sequencing. JAMA Oncol 2(8):1070–1074CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Lee D. Gibbs
    • 1
    • 4
    Email author
  • Pankaj Chaudhary
    • 1
  • Kelsey Mansheim
    • 2
  • Richard J. Hare
    • 3
  • Rebecca A. Mantsch
    • 3
  • Jamboor K. Vishwanatha
    • 1
  1. 1.Institute for Molecular Medicine, Texas Center for Health DisparitiesUniversity of North Texas Health Science CenterFort WorthUSA
  2. 2.Department of PathologyBrookwood Baptist HealthBirminghamUSA
  3. 3.Department of PathologyMedical City Fort WorthFort WorthUSA
  4. 4.Keck School of Medicine of University of Southern CaliforniaLos AngelesUSA

Personalised recommendations