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In situ identification and localization of IGHA2 in the breast tumor microenvironment by mass spectrometry

 Suki Kang  ;  Heysun Maeng  ;  Baek Gil Kim  ;  Gao Ming Qing  ;  Yoon Pyo Choi  ;  Hak Yong Kim  ;  Pan Soo Kim  ;  Yangsun Kim  ;  Young Hwan Kim  ;  Young Deuk Choi  ;  Nam Hoon Cho 
 JOURNAL OF PROTEOME RESEARCH, Vol.11(9) : 4567-4574, 2012 
Journal Title
Issue Date
Biomarkers, Tumor ; Breast/chemistry ; Breast/pathology ; Breast Neoplasms/chemistry* ; Breast Neoplasms/metabolism ; Carrier Proteins/analysis* ; Carrier Proteins/chemistry ; Female ; Humans ; Immunoglobulin Heavy Chains/analysis* ; Immunoglobulin Heavy Chains/chemistry ; Immunohistochemistry ; Molecular Imaging/methods ; Neoplasm Metastasis ; Reproducibility of Results ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods* ; Tandem Mass Spectrometry/methods ; Tumor Microenvironment/physiology*
breast cancer ; IGHA2 ; MALDI-MSI ; tissue MALDI MS/MS ; tumor microenvironment
Modifications in the tumor microenvironment (TME) play a major role in the establishment, progression, and metastasis of cancer. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is a powerful technique that enables the simultaneous identification and localization of biological compounds within tissues. To detect markers of early TME remodeling in invasive breast cancer, we used MALDI-MSI to compare the molecular profiles of tissues from the breast cancer interface zone, tumor zone, and normal-tissue zone. Using direct-tissue MALDI tandem mass spectrometry (MS/MS), we identified immunoglobulin heavy constant alpha 2 (IGHA2) as a new, zone-specific protein in the breast TME. The zone-specific expression of IGHA2 was verified by immunoblotting and immunohistochemical analysis. IGHA2 expression was consistently positive in tumor cells that were metastatic to regional nodes, with intense expression along the cytoplasmic borders. As a factor related to an increased percentage of nodes with tumor metastasis, IGHA2 expression was upregulated 3.745-fold in cases with an increased number of cancerous nodes (p = 0.0468). Our results provide the first evidence of IGHA2 as a marker of the early process of TME remodeling in invasive breast cancer. Furthermore, IGHA2 may be a novel marker for regional metastases in the lymph nodes of patients with breast cancer.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kang, Suki(강숙희) ORCID logo https://orcid.org/0000-0002-9957-3479
Gao, Ming Qing(고명청)
Kim, Baek Gil(김백길) ORCID logo https://orcid.org/0000-0001-6270-1433
Cho, Nam Hoon(조남훈) ORCID logo https://orcid.org/0000-0002-0045-6441
Choi, Young Deuk(최영득) ORCID logo https://orcid.org/0000-0002-8545-5797
Choi, Yoon Pyo(최윤표)
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