SummaryExpression of carboxypeptidase E, a prohormone processing enzyme in different cancer types was analyzed from data in the GEO profile database, and experimentally in pheochromocytomas. Microarray data from the GEO profile database indicated that significantly elevated levels of CPE mRNA was found in many non-endocrine cancers: cervical, colon rectal, renal cancers, Ewing sarcomas (bone cancer) and various types of astrocytomas and oligodendrogliomas, but expression of CPE mRNA was virtually absent in their respective counterpart normal tissues. Moreover there was a good correlation of high CPE mRNA expression with metastasis in cervical cancer and anaplastic oligodendrogliomas and neoplastic astrocytomas. Elevated CPE mRNA expression was found in neuroendocrine tumors in lung and pituitary adenomas, although the significance is unclear since endocrine and neuroendocrine cells normally express CPE. However studies of a neuroendocrine tumor, pheochromocytoma, revealed expression of not only wild type CPE, but a variant which was correlated with tumor behavior. Extremely high CPE mRNA copy numbers of the variant were found in very large or invasive tumors, both of which usually indicate poor prognosis. Thus, all the data suggest that CPE is involved in tumorogenesis and that it may play a role in promoting tumor growth and invasion. CPE could potentially serve as a diagnostic and prognostic biomarker for different cancer types.