Extracellular Matrix Imaging of Breast Tissue Pathologies by MALDI Imaging Mass Spectrometry.

PURPOSE: We recently reported a new method accessing proteins from extracellular matrix by imaging mass spectrometry (ECM IMS). ECM IMS was evaluated for use in exploring breast tissue pathologies.

EXPERIMENTAL DESIGN: A tissue microarray (TMA) was analyzed that had 176 cores of biopsies and lumpectomies spanning breast pathologies of inflammation, hyperplasia, fibroadenoma, invasive ductal carcinoma and invasive lobular carcinoma and normal adjacent to tumor (NAT). NAT was compared to subtypes by area under the receiver operating curve (ROC) >0.7. A lumpectomy was also characterized for collagen organization by microscopy and stromal protein distribution by IMS. LC-based high-resolution accurate mass (HRAM) proteomics was used to identify proteins from the lumpectomy.

RESULTS: TMA analysis showed distinct spectral signatures reflecting a heterogeneous tissue microenvironment. Ninety-four peaks showed a ROC >0.7 compared to NAT; NAT had overall higher intensities. Lumpectomy analysis by IMS visualized a complex central tumor region with distal tumor regions. HRAM LC-based proteomics identified 39 stromal proteins. Accurate mass matches between image data and LC-based proteomics demonstrated a heterogeneous collagen type environment in the central tumor.

CONCLUSIONS: Data portray the heterogeneous stromal microenvironment of breast pathologies, including alteration of multiple collagen type patterns. ECM IMS is a promising new tool for investigating the stromal microenvironment of breast tissue including cancer. This article is protected by copyright. All rights reserved.