LA-ICP-MS analysis reveals differences in chemotherapeutic drug distribution in surgically resected pleural mesothelioma

Background and Purpose: Pleural mesothelioma (PM) is a highly aggressive thoracic tumor with poor prognosis. Although reduced tissue drug accumulation is one of the key features of platinum (Pt) resistance, little is known about Pt distribution in human PM. Experimental Approach: We assessed Pt levels of blood samples and surgically resected specimens from 25 PM patients who had received neoadjuvant Pt-based chemotherapy (CHT). Pt levels and tissue distributions were measured by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and correlated with clinicopathological features. Key Results: In surgically resected PM specimens, mean Pt levels were significantly higher in the non-tumorous (fibrotic) areas (vs. tumorous regions, p<0.001). No major heterogeneity of Pt distribution was seen within the tumorous areas. Pt levels correlated neither with microvessel area (MVA) nor with apoptosis rate in the tumorous or in the non-tumorous regions. A significant positive correlation was found between serum and both full tissue section and tumorous area average Pt levels (r=0.415, p=0.039 and r=0.532, p=0.006, respectively). Furthermore, a significant negative correlation was detected between serum Pt concentrations and elapsed time from the last cycle of CHT (r=-0.474, p=0.017). Serum Pt levels correlated negatively with overall survival (OS) (p=0.029). Conclusion and Implications: There are major differences in the drug distribution between tumorous and non-tumorous areas of PM specimens. Serum Pt levels significantly correlate with full section- and tumorous areas average Pt levels, elapsed time from the last CHT cycle, and OS. Further studies investigating clinicopathological factors that modulate tissue Pt concentration and distribution are warranted.