Neuroendocrine cancer of the kidney: Clinical implications of expression microarray analysis

Abstract

20093 Background: Conventional clinical trial strategies cannot be used to develop new therapies for rare malignancies. Neuroendocrine neoplasms of the kidney are extremely rare. Here we compare the gene expression profiles of a neuroendocrine tumor from a 32 year old male with a horseshoe kidney, a large renal primary and metastatic thyroid lesions to the profiles of other cancers. Response to systemic therapy is also reported. The ultimate objective of this project is to identify new therapeutic targets for patient-specific cancer therapy. Methods: After informed consent, tissue from the patient was analyzed by cytology and immunohistochemistry. Total RNA was isolated from formalin-fixed paraffin-embedded archival reference tissues with Arcturus Paradise Reagents. Gene expression was analyzed with Affymetrix X3P arrays of the entire expressed genome. A supervised significance analysis of microarrays (SAM) procedure, using 400 data permutations, was performed to identify gene products that were differentially expressed. Clinical outcomes were documented in the patient’s medical record on the basis of standard medical imaging. Results: Cytology, immunohistochemistry and microarray studies revealed similar patterns for the primary and metastatic lesions. Gene expression profiles of the patient’s kidney and thyroid lesions, as well as other kidney and neuroendocrine tumors, identified 11 genes overexpressed significantly in the neuroendocrine tumors. Each was associated with neuroendocrine biology. The patient had a mixed response to chemotherapy with gemcitabine and cisplatin and progressive disease after 3 monthly treatments with sandostatin. He awaits assessment of response to metaiodobenzylguanidine (MIBG). Conclusions: Gene expression profiling was effective in characterizing an unusual case of renal cancer with metastasis to thyroid, though no new therapeutic target has yet been identified. Comparing response or resistance to therapy with microarray analysis may prove to be an effective strategy for developing patient-specific cancer therapy. This work was supported, in part, by a VA Merit Review Award. No significant financial relationships to disclose.