Journal
NEUROENDOCRINOLOGY
Volume 101, Issue 2, Pages 151-160Publisher
KARGER
DOI: 10.1159/000375449
Keywords
Mixed carcinoma; Neuroendocrine carcinoma; Gene expression; Thymidylate synthase; Prognosis
Categories
Funding
- Italian Association for Cancer Research (AIRC) [IG 13567]
Ask authors/readers for more resources
Background: Mixed neuroendocrine/nonneuroendocrine carcinomas are heterogeneous tumors with poorly defined diagnostic and clinical features and without pathological or molecular markers of prognosis or markers predicting their response to therapy. We aimed at analyzing the pathological features and the expression of genes involved in DNA repair or synthesis in a cohort of patients with mixed carcinomas from different sites as compared to the patients' outcome. Methods: Relative cDNA quantification of ribonucleotide reductase, large subunit 1, excision repair cross-complementation group 1, thymidylate synthase and topoisomerase Ila genes was tested using real-time PCR on microdissected neuroendocrine and nonneuroendocrine tumor components of 42 mixed cases (from the lung as well as the gastrointestinal and genitourinary tracts) and on 45 control cases of pure neuroendocrine and nonneuroendocrine carcinomas. Results: The expression levels of all genes were stable comparing nonneuroendocrine and neuroendocrine components of mixed cases (except for topoisomerase Ha in lung samples) but significantly different as compared to control nonneuroendocrine and neuroendocrine tumors. In the multivariate analysis including all clinical and pathological parameters and gene expression levels available, a predominant nonneuroendocrine component, the administration of additional therapy other than surgery and a high thymidylate synthase expression in nonneuroendocrine tumor tissue were significantly associated with a lower risk of a patient's death. Conclusions: Our data show that mixed neuroendocrine/nonneuroendocrine carcinomas are different at the molecular level from their pure neuroendocrine and nonneuroendocrine counterparts, and detailed analyses of their clinical, pathological and molecular features may improve the clinical strategies for the treatment of these rare and underestimated tumors. (C) 2015S. Karger AG, Basel
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available