Proteomic membrane profiling of malignant and benign adrenal tumours

Hanna Eriksson, Johan Lengqvist, Janne Lehtiö and Magnus Kjellman (Department of Surgery, KI, Solna, Sweden)

The adrenal cortex is responsible for synthesizing and secreting several different classes of hormones, including glucocorticoids, mineralocorticoids, and sex steroids. These hormones and their metabolites play essential roles in regulating multiple processes throughout the body, including glucose metabolism, fluid-electrolyte balance, inflammation, wound healing and sexual development. Adrenocortical neoplasms are classified as adenomas or carcinomas. Adrenocortical carcinoma is a rare neoplasm with a worldwide incidence of approximately two per million inhabitants. These neoplasms are aggressive with a poor prognosis; the overall 5-year survival rate has been estimated as less than 40%. Adrenocortical adenomas are much more frequent and have a better prognosis. It is often hard to distinguish between adenomas and carcinomas. Up to date, the most important feature to predict malignant behavior is tumor size; carcinomas are usually larger, weigh more, and frequently have necrosis. On the other hand, only two out of one million tumors develop into malignant cancers. A complete surgical resection is currently the only cure for malignant neoplasms and thus, these patients are subjects for surgery with the concomitant risks and high costs that could be avoided if biomarkers were available.

The aim of this project is to investigate the differences in the microsomal proteome of adrenocortical adenomas and carcinomas. Differences in the plasma membrane proteome could be used for developing imaging analyses. Material is obtained from surgeries performed at the Karolinska University Hospital. Sub-cellular protein fractions are prepared and proteins are digested into peptides. These peptides are labeled with iTRAQ and subsequently separated according to pI. Proteins are identified and quantified with mass spectrometry.

Last updated: 2008-01-10