Abstract

A set of basal cell carcinoma samples, removed by Mohs micrographic surgery and pathologically identified as having an aggressive subtype, have been analyzed using time-of-flight secondary ion mass spectrometry (SIMS). The SIMS analysis employed a gas cluster ion beam (GCIB) to increase the sensitivity of the technique for the detection of intact lipid species. The GCIB also allowed these intact molecular signals to be maintained while surface contamination and delocalized chemicals were removed from the upper tissue surface. Distinct mass spectral signals were detected from different regions of the tissue (epidermis, dermis, hair follicles, sebaceous glands, scar tissue, and cancerous tissue) allowing mass spectral pathology to be performed. The cancerous regions of the tissue showed a particular increase in sphingomyelin signals that were detected in both positive and negative ion mode along with increased specific phosphatidylserine and phosphatidylinositol signals observed in negative ion mode. Samples containing mixed more and less aggressive tumor regions showed increased phosphatidylcholine lipid content in the less aggressive areas similar to a punch biopsy sample of a nonaggressive nodular lesion.

Highlights

  • Basal cell carcinoma (BCC) is the most common cancer in humans.1 The BCC incidence is reported to be between 77 and 158 per 100 000 person years in Europe.2 The incidence in Sweden has increased almost tenfold over the last 30 years

  • The erosion rate, and analysis depth, was not measured for this sample but for comparison this would correspond to the removal of approximately 75 nm of Irganox 1010.14,21,22

  • It is shown that the use of gas cluster ion beam (GCIB) allows detection of intact lipid species at high primary ion dose density so intact molecular imaging can be performed

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Summary

INTRODUCTION

Basal cell carcinoma (BCC) is the most common cancer in humans. The BCC incidence is reported to be between 77 and 158 per 100 000 person years in Europe. The incidence in Sweden has increased almost tenfold over the last 30 years. In regards to BCC, studies have shown that there are significantly increased levels of total lipids and phospholipids in these tumors when compared to healthy skin tissue.. The ionization efficiency of secondary species is low when used at low energy, GCIBs provided a Â30–50 increase in intact lipid signal per primary ion on rodent brain compared with C60þ when both beams were accelerated through 40 kV.. The ionization efficiency of secondary species is low when used at low energy, GCIBs provided a Â30–50 increase in intact lipid signal per primary ion on rodent brain compared with C60þ when both beams were accelerated through 40 kV.14 These technological advances have greatly enhanced the capabilities of SIMS for probing complex biological systems such as drug effects on Drosophila brain, chemical changes in breast cancer biopsy tissue, bacteria, and cardiolipins in rodent brain.. Differences between high and low aggressive tumors were identified

Tissue preparation
ToF-SIMS analysis
Multivariate analysis
Investigating dose-dependent signal from the tissue
Maximum autocorrelation factor analysis
Cross patient comparison
SUMMARY AND CONCLUSIONS

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