Characteristic lipid profiles of canine non-Hodgkin's lymphoma from surgical biopsy tissue sections and fine needle aspirate smears by desorption electrospray ionization – mass spectrometry

Abstract

Canine non-Hodgkin's lymphoma (NHL) is a heterogeneous group of cancers representing approximately 15% of all canine cancers. Further, canine NHL mimics human disease in regards to histopathology and clinical behavior and could function as a comparative model. Diagnosis is currently performed by histopathological evaluation of surgical biopsy specimens and fine needle aspirate (FNA) cytology, an alternative and less invasive method for diagnosis. Desorption electrospray ionization - mass spectrometry (DESI-MS) imaging was performed on tissue sections of surgical biopsies and FNA smears. Mass spectra acquired from normal lymph nodes and NHL tumors were explored using multivariate statistics (e.g. principal component analysis). Tissue sections yielded a predicted sensitivity of 100% for normal and 93.1% for tumor. Further, preliminary results suggest B-cell and T-cell lymphoma can be discriminated (CV sensitivity of 95.5% and 85.7%, respectively). Normal and B-cell NHL FNA samples analyzed by DESI produced spectra that were similar to spectra obtained from surgical biopsies. FNA samples were evaluated using a PCA-LDA classification system built using tissue section data, exploring if the chemical information obtained from the different sample types is similar and whether DESI-MS performed on FNA samples is of diagnostic value. FNA prediction rate for normal (85.7%) and B-cell NHL (89.3%) indicated that DESI-MS analysis of FNA, not previously explored, could provide rapid preliminary diagnosis. Certainly, MS provides complementary molecular information to be used in conjunction with histopathology/cytology, potentially improving diagnostic confidence. The methodology outlined here is applicable to canine NHL, further supports canine models of human NHL, and translation to humans is envisioned.

Lipid dynamics in zebrafish embryonic development observed by DESI-MS imaging and nanoelectrospray-MS

“…The capabilities of DESI for tissue and microscopic embryo analysis are increased significantly by the use of non-destructive solvent systems that allow desorption of lipids and small molecules while the intracellular and extracellular proteins are preserved, allowing multi-analytical approaches 13,14 . To date, DESI has been used to study prostate 15 , bladder, kidney 16 , gastric 17 , and brain cancers 18 , as well as lymphoma 19 . In each case, the recorded pattern of lipid signals allowed for differentiation of cancer from normal tissue.…”

Lipid and metabolite profiles of human brain tumors by desorption electrospray ionization-MS

“…To date, DESI-MS analysis of tissue and cytological smears has been only briefly explored (7,33). Smears are commonly performed by placing a minute amount of tissue onto a glass slide and then physically spreading the material to achieve a relatively uniform and diffuse layer of cellular material for staining and subsequent pathology.…”

“…Previous studies (3)(4)(5)(6)(7)(8)(9)(10)(11) have shown tissue discrimination by mass spectral profiles (m/z values and associated abundances) characteristic of different tissue types, including different disease states. Rapid and direct analysis of tissue provides molecular information on multiple compounds and is obtained on a timescale of seconds to a few minutes.…”

“…This feature allows integration of DESI-MS into current workflows and postacquisition pathology. DESI-MS has been used to study prostate cancer (3), bladder cancer (4), kidney cancer (5), seminoma (6), lymphoma (7), gastrointestinal cancer (8), and others. In each case, the recorded pattern of lipid signals allows the differentiation of cancer from normal tissue.…”

Ambient Mass Spectrometry Imaging Using Direct Liquid Extraction Techniques

“…161,168–171 In a related study, DESI MSI of surgical biopsies has been used for diagnostics of human breast cancer 171 and canine non-Hodgkin’s lymphoma. 172 …”