A Molecular Assessment of Tumor Margins by MALDI Mass Spectrometry in Renal Carcinoma
Oppenheimer, Stacey Renee
The identification of tumor margins is vital for successful patient outcome, preventing local recurrence and ensuring long-term survival. Current techniques used to assess tumor margins for successful tumor removal require contrast agents and histological analyses; however, many tumors recur due to incomplete tumor removal or a precursor lesion left behind which may subsequently evolve into an invasive tumor. Antibody-based approaches to assessing tumor margins often suffer from unknown cross-reactivities, while nuclear staining procedures are limited to visualization of the morphological characteristics of cells. The rate of tumor recurrence post resection suggests that there are underlying molecular changes that go undetected in conventional diagnostic methods. To determine and better understand the molecular changes in and around the tumor margin requires the application of molecular technologies. MALDI MS is a molecular technology that has the specificity and sensitivity to monitor and identify molecular signatures indicative of these processes. Profiling and imaging MALDI MS technology has been applied to multiple diseased tissues and, with biocomputational tools, has resulted in the identification of disease-state and patient prognostic-specific protein patterns. The study presented in this thesis utilized profiling MALDI MS to assess molecular distributions within the tumor, adjacent normal, and histological tumor margin in clear cell renal cell carcinoma biopsies to characterize atypical molecular features present in the normal appearing tissue outside the histological tumor margin. Results indicated that the histologically normal appearing tissue adjacent to the histological tumor border expresses molecular characteristics of the tumor. Protein identification revealed that several constituents of the mitochondrial electron transport system were involved. These proteins were under-expressed in tumor and the surrounding normal tissue, suggesting a crucial role of the mitochondrial electron transport chain in clear cell renal cell carcinoma tumor invasion. This study demonstrates the advantage of using MALDI MS to characterize molecular signatures in the tumor microenvironment. Further, the methods used for this study can be adapted to the molecular assessment of tumor margins in other cancers as well.