Imaging mass spectrometry to discriminate breast from pancreatic cancer metastasis in formalin‐fixed paraffin‐embedded tissues

Abstract

Diagnosis of the origin of metastasis is mandatory for adequate therapy. In the past, classification of tumors was based on histology (morphological expression of a complex protein pattern), while supportive immunohistochemical investigation relied only on few "tumor specific" proteins. At present, histopathological diagnosis is based on clinical information, morphology, immunohistochemistry, and may include molecular methods. This process is complex, expensive, requires an experienced pathologist and may be time consuming. Currently, proteomic methods have been introduced in various clinical disciplines. MALDI imaging MS combines detection of numerous proteins with morphological features, and seems to be the ideal tool for objective and fast histopathological tumor classification. To study a special tumor type and to identify predictive patterns that could discriminate metastatic breast from pancreatic carcinoma MALDI imaging MS was applied to multitissue paraffin blocks. A statistical classification model was created using a training set of primary carcinoma biopsies. This model was validated on two testing sets of different breast and pancreatic carcinoma specimens. We could discern breast from pancreatic primary tumors with an overall accuracy of 83.38%, a sensitivity of 85.95% and a specificity of 76.96%. Furthermore, breast and pancreatic liver metastases were tested and classified correctly.

Reliable Entity Subtyping in Non-small Cell Lung Cancer by Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry on Formalin-fixed Paraffin-embedded Tissue Specimens

“…Promising results using this technology could be obtained in several diseases and different types of cancer (9,(22)(23)(24).…”

Mass Spectrometry Imaging of Biomolecular Information

“…FFPE samples can be analyzed and imaged after direct tryptic digestion 154 or after heat-induced antigen retrieval, dewaxing an digestion 155 . MALDI MSI of FFPE tissue has been reported in great numbers recently 10,[156][157][158][159][160][161][162][163][164][165][166][167][168][169][170][171][172][173] . To mention just one example: ovarian cancer FFPE samples were investigated to describe progression, metastases and other factors of cancer development by topographic parameters and molecular information 169 .…”

MALDI mass spectrometry imaging: A cutting‐edge tool for fundamental and clinical histopathology

“…This method was described in detail in the Supporting data. Together with other mathematical methods, such as principal component analysis (PCA) , and other classification tools , MSI investigations are now strengthened by reliable statistics.…”