Abstract
Parotid cancer is relatively rare, and malignancy varies; therefore, novel markers are needed to predict prognosis. Recent advances in matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), useful for visualization of lipid molecules, have revealed the relationship between cancer and lipid metabolism, indicating the potential of lipids as biomarkers. However, the distribution and importance of phospholipids in parotid cancer remain unclear. This study aimed to use MALDI-IMS to comprehensively investigate the spatial distribution of phospholipids characteristically expressed in human parotid cancer tissues. Tissue samples were surgically collected from two patients with parotid cancer (acinic cell carcinoma and mucoepidermoid carcinoma). Frozen sections of the samples were assessed using MALDI-IMS in both positive and negative ion modes, with an m/z range of 600-1000. The mass spectra obtained in the tumor and non-tumor regions were compared and analyzed. Ion images corresponding to the peak characteristics of the tumor regions were visualized. Several candidate phospholipids with significantly different expression levels were detected between the tumor and non-tumor regions. The number of unique lipid peaks with significantly different intensities between the tumor and non-tumor regions was 95 and 85 for Cases 1 and 2, respectively, in positive ion mode, and 99 and 97 for Cases 1 and 2, respectively, in negative ion mode. Imaging differentiated the characteristics that phospholipids were heterogeneously distributed in the tumor regions. Phospholipid candidates that are characteristically expressed in human parotid cancer tissues were found, demonstrating the localization of their expression. These findings are notable for further investigation of alterations in lipid metabolism of parotid cancer and may have potential for the development of phospholipids as biomarkers.
Highlights
Parotid cancer, the most common salivary gland cancer, has various histological types and grades of malignancy [1, 2]
hematoxylin and eosin (HE) staining in Case 1 revealed serous glandular cell-like tumor cells with hematoxylin-stained basophilic granules in the cytoplasm, which proliferated in a solid pattern (S1C Fig)
In Case 2, the tumor was approximately 4 cm in diameter, the cut surface was bifid, and numerous cystic spaces filled with mucus were observed (S1B Fig)
Summary
The most common salivary gland cancer, has various histological types and grades of malignancy [1, 2]. Because of its clinical and histological variety, it is difficult to estimate the malignancy grade and histological type preoperatively [3]. The improvement of clinical and pathological diagnosis, and prognostic estimation methods for parotid cancer are necessary to provide appropriate treatment according to the grade of malignancy. The carcinogenic mechanism of parotid cancer remains unclear because of its rarity and variety of histological types. The role of lipid molecules in biological functions has been clarified, and the importance of the relationship between cancer and lipid metabolism has attracted much attention [8,9,10]. The distribution and importance of phospholipids in parotid cancer remain unclear
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