The Precise Diagnosis of Cancer Invasion/Metastasis via 2D Laser Ablation Mass Mapping of Metalloproteinase in Primary Cancer Tissue.

Abstract

Cancer invasion and metastasis remain the major causes of over 90% of patient deaths. Molecular imaging methods such as computed tomography (CT)/magnetic resonance imaging (MRI) can precisely assess primary regional lymph node invasion and distant organ metastasis via body scanning; however, such diagnostic methods are often utilized too late for cancer therapy. To date, pathologic methods mainly provide information on differentiation/proliferation and potential drug therapy biomarkers of primary tumors rather than precisely reveal tumor regional invasion and distant metastasis in the body. We hypothesized that quantification of membrane type-1 matrix metalloproteinase (MT1-MMP) levels in primary tumor tissue will provide a precise assessment of tumor regional lymph node invasion and remote organ metastasis. In this work, we developed peptide-coated Au clusters with intrinsic red fluorescence and a specific mass signal. When these clusters labeled MT1-MMP in tumor tissue sections derived from the xenograft lung carcinoma model, human lung carcinoma and human renal carcinoma, we could directly observe MT1-MMP via optical fluorescence microscopy and quantitatively detect the MT1-MMP expression level via laser ablation inductively coupled plasma mass spectrometry 2D mapping (2D-LA-Mass Mapping). By observing and quantifying the MT1-MMP expression level in primary human lung carcinoma and human renal carcinoma tissue sections, we precisely assessed the risk of primary tumor invasion/metastasis. Importantly, the accuracy of this pathologic method was verified by CT/MRI molecular imaging of cancer patients and traditional hematoxylin and eosin (H&E) staining/immunohistochemistry (IHC)/immunofluorescence (IF) pathologic studies of primary tumor tissues.