In situ identification and localization of IGHA2 in the breast tumor microenvironment by mass spectrometry.
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.
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Suki
S
Kang
Heysun
H
Maeng
Baek Gil
BG
Kim
Gao Ming
GM
Qing
Yoon Pyo
YP
Choi
Hak Yong
HY
Kim
Pan Soo
PS
Kim
Yangsun
Y
Kim
Young Hwan
YH
Kim
Young Deuk
YD
Choi
Nam Hoon
NH
Cho
D014408:Biomarkers, Tumor; D001940:Breast / Q000737:chemistry / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry* / Q000378:metabolism; D002352:Carrier Proteins / Q000032:analysis* / Q000737:chemistry; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis* / Q000737:chemistry; D007150:Immunohistochemistry; D057054:Molecular Imaging / Q000379:methods; D009362:Neoplasm Metastasis; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods; D059016:Tumor Microenvironment / Q000502:physiology*
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D007143:Immunoglobulin Heavy Chains