Y-Box binding protein 1 expression in breast cancer and its correlation with hormone receptors and other prognostic markers

Taruna Bansal; Nadeem Tanveer; Usha Rani Singh; Sonal Sharma; Navneet Kaur

doi:10.4103/JLP.JLP_58_18

Journal of Laboratory Physicians, Table of Contents

CC BY-NC-ND 4.0 · J Lab Physicians 2018; 10(04): 420-425
DOI: 10.4103/JLP.JLP_58_18

Original Article

Y-Box binding protein 1 expression in breast cancer and its correlation with hormone receptors and other prognostic markers

Taruna Bansal

Department of Pathology, University College of Medical Sciences, New Delhi, India

,

Nadeem Tanveer

Department of Pathology, University College of Medical Sciences, New Delhi, India

,

Usha Rani Singh

Department of Pathology, University College of Medical Sciences, New Delhi, India

,

Sonal Sharma

Department of Pathology, University College of Medical Sciences, New Delhi, India

,

Navneet Kaur

Department of Surgery, University College of Medical Sciences, New Delhi, India

› Author Affiliations

Abstract

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Abstract

INTRODUCTION: The present histologic and immunohistochemical prognostic markers of breast carcinoma do not effectively identify the subset of patients with poor prognosis. Y-Box binding protein 1 (YB1) is a novel biomarker which may identify and aid in targeted personalized therapy for such patients.

MATERIALS AND METHODS: The study was conducted on histopathology specimens of 74 patients of breast carcinoma who had undergone modified radical mastectomy. YB1 immunohistochemistry (IHC) was performed on manual tissue microarray blocks (each having 15 cores). The YB1 expression was quantified in terms of “immunoreactive score” which was correlated with clinical parameters, hormone receptor status, and Her2neu overexpression by IHC. The Her2neu status of the equivocal cases was further evaluated by fluorescent in situ hybridization (FISH).

RESULTS: YB1 was positive in 36/74 (48.6%) cases. On IHC and analysis by FISH, 25/74 (34%) cases had Her2neu overexpression. Estrogen receptor (ER) and progesterone receptor (PR) positivity was found in 42% and 36.5% cases, respectively. YB1 immunopositivity was negatively correlated with ER and PR expression, but showed a significant positive correlation with Her2neu expression. No correlation was found with other clinical parameters, tumor stage, and grade, except lymph node involvement, which showed a positive association with YB1 expression. Triple-negative breast carcinoma constituted 25.6% of the total cases, out of which 73.6% were YB1 positive.

CONCLUSION: This study found that YB1 has an association with Her2neu expression. It may in future provide a therapeutic target in Her2neu overexpressing tumors.

Keywords

Manual tissue microarray - triple-negative breast carcinoma - Y-Box binding protein 1

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References

References
1 Liu X, Pogo BG. Inhibition of erbB-2-positive breast cancer cell growth by erbB-2 antisense oligonucleotides. Antisense Nucleic Acid Drug Dev 1996;6:9-16.
2 Lasham A, Samuel W, Cao H, Patel R, Mehta R, Stern JL, et al. YB-1, the E2F pathway, and regulation of tumor cell growth. J Natl Cancer Inst 2012;104:133-46.
3 Bouvet P, Matsumoto K, Wolffe AP. Sequence-specific RNA recognition by the xenopus Y-box proteins. An essential role for the cold shock domain. J Biol Chem 1995;270:28297-303.
4 Sakura H, Maekawa T, Imamoto F, Yasuda K, Ishii S. Two human genes isolated by a novel method encode DNA-binding proteins containing a common region of homology. Gene 1988;73:499-507.
5 Bargou RC, Jürchott K, Wagener C, Bergmann S, Metzner S, Bommert K, et al. Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression. Nat Med 1997;3:447-50.
6 Stein U, Jürchott K, Walther W, Bergmann S, Schlag PM, Royer HD, et al. Hyperthermia-induced nuclear translocation of transcription factor YB-1 leads to enhanced expression of multidrug resistance-related ABC transporters. J Biol Chem 2001;276:28562-9.
7 Evdokimova VM, Ovchinnikov LP. Translational regulation by Y-box transcription factor: Involvement of the major mRNA-associated protein, p50. Int J Biochem Cell Biol 1999;31:139-49.
8 Bergmann S, Royer-Pokora B, Fietze E, Jürchott K, Hildebrandt B, Trost D, et al. YB-1 provokes breast cancer through the induction of chromosomal instability that emerges from mitotic failure and centrosome amplification. Cancer Res 2005;65:4078-87.
9 Habibi G, Leung S, Law JH, Gelmon K, Masoudi H, Turbin D, et al. Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes. Breast Cancer Res 2008;10:R86.
10 Wu J, Stratford AL, Astanehe A, Dunn SE. YB-1 is a transcription/Translation factor that orchestrates the oncogenome by hardwiring signal transduction to gene expression. Transl Oncogenomics 2007;2:49-65.
11 Woolley AG, Algie M, Samuel W, Harfoot R, Wiles A, Hung NA, et al. Prognostic association of YB-1 expression in breast cancers: A matter of antibody. PLoS One 2011;6:e20603.
12 Fehm T, Morrison L, Saboorian H, Hynan L, Tucker T, Uhr J, et al. Patterns of aneusomy for three chromosomes in individual cells from breast cancer tumors. Breast Cancer Res Treat 2002;75:227-39.
13 Wang X, Guo XB, Shen XC, Zhou H, Wan DW, Xue XF, et al. Prognostic role of YB-1 expression in breast cancer: A meta-analysis. Int J Clin Exp Med 2015;8:1780-91.
14 Lantz E, Cunningham I, Higa GM. Targeting HER2 in breast cancer: Overview of long-term experience. Int J Womens Health 2010;1:155-71.
15 Ménard S, Fortis S, Castiglioni F, Agresti R, Balsari A. HER2 as a prognostic factor in breast cancer. Oncology 2001;61 Suppl 2:67-72.
16 Wu J, Lee C, Yokom D, Jiang H, Cheang MC, Yorida E, et al. Disruption of the Y-box binding protein-1 results in suppression of the epidermal growth factor receptor and HER-2. Cancer Res 2006;66:4872-9.
17 Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: Experience from a large study with long-term follow-up. Histopathology 1991;19:403-10.
18 Singletary SE, Connolly JL. Breast cancer staging: Working with the sixth edition of the AJCC cancer staging manual. CA Cancer J Clin 2006;56:37-47.
19 Chen N, Zhou Q. Constructing tissue microarrays without prefabricating recipient blocks: A novel approach. Am J Clin Pathol 2005;124:103-7.
20 Kononen J, Bubendorf L, Kallioniemi A, Bärlund M, Schraml P, Leighton S, et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 1998;4:844-7.
21 Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline update. Arch Pathol Lab Med 2014;138:241-56.
22 Zhao S, Wang Y, Guo T, Yu W, Li J, Tang Z, et al. YBX1 regulates tumor growth via CDC25a pathway in human lung adenocarcinoma. Oncotarget 2016;7:82139-57.
23 Moasser MM. The oncogene HER2: Its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene 2007;26:6469-87.
24 Mitri Z, Constantine T, O’Regan R. The HER2 receptor in breast cancer: Pathophysiology, clinical use, and new advances in therapy. Chemother Res Pract 2012;2012:743193.
25 Xie W, Yang J, Cao Y, Peng C, Ning H, Zhang F, et al. Expression of Y-box-binding protein 1 in Chinese patients with breast cancer. Tumour Biol 2012;33:63-71.
26 Davies AH, Barrett I, Pambid MR, Hu K, Stratford AL, Freeman S, et al. YB-1 evokes susceptibility to cancer through cytokinesis failure, mitotic dysfunction and HER2 amplification. Oncogene 2011;30:3649-60.
27 Fujii T, Kawahara A, Basaki Y, Hattori S, Nakashima K, Nakano K, et al. Expression of HER2 and estrogen receptor alpha depends upon nuclear localization of Y-box binding protein-1 in human breast cancers. Cancer Res 2008;68:1504-12.
28 Mylona E, Melissaris S, Giannopoulou I, Theohari I, Papadimitriou C, Keramopoulos A, et al. Y-box-binding protein 1 (YB1) in breast carcinomas: Relation to aggressive tumor phenotype and identification of patients at high risk for relapse. Eur J Surg Oncol 2014;40:289-96.