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Proceedings Paper

Histology-directed MALDI mass spectrometry for the diagnostic pathology
Author(s): Hark Kyun Kim; In-Hoo Kim
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Paper Abstract

With the advent of targeted agents, it has become clinically important to distinguish histologic types of non-small cell lung cancers (NSCLCs) using biopsy samples. We investigated whether direct tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis on lipid may classify histology of NSCLCs. Twentyone pairs of frozen, resected NSCLCs were analyzed using histology-directed, MALDI MS. 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. Squamous cell carcinomas and adenocarcinomas, two major histologic types of NSCLC, were found to have different lipid profiles. Discriminatory lipids correctly classified the histology of 80.4% of independent NSCLC surgical tissue samples (41 out of 51) in validation set, suggesting that lipid profiles can classify NSCLCs according to the histologic type. We also found that protein and lipid MALDI MS profiles can classify 30 breast cancers according to the intrinsic subtypes. Immunohistochemistry-defined, luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by cross validation P values < 0.01. Discriminatory proteins and lipids classified tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in 100 random test sets. Potential advantages of this label-free approach may include small tissue requirement, relatively rapid procedure, and low reagent cost. Day-today variation of this technology is also acceptable, with the Pearson correlation of 0.95. Taken together, these results suggest the possible clinical utility of histology-directed, lipid and protein MALDI MS.

Paper Details

Date Published: 24 October 2012
PDF: 6 pages
Proc. SPIE 8548, Nanosystems in Engineering and Medicine, 854823 (24 October 2012); doi: 10.1117/12.1000001
Show Author Affiliations
Hark Kyun Kim, National Cancer Ctr. (Korea, Republic of)
In-Hoo Kim, National Cancer Ctr. (Korea, Republic of)

Published in SPIE Proceedings Vol. 8548:
Nanosystems in Engineering and Medicine
Sang H. Choi; Jin-Ho Choy; Uhn Lee M.D.; Vijay K. Varadan, Editor(s)

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