AI Article Synopsis

  • Mixed neuroendocrine/nonneuroendocrine carcinomas are complex tumors with unclear features and no definitive prognostic markers, prompting a study on their pathology and gene expression related to DNA repair.
  • The research involved analyzing 42 mixed carcinoma cases and 45 controls, focusing on specific genes using real-time PCR, revealing significant molecular differences between mixed and pure tumors.
  • Findings suggest that a dominant nonneuroendocrine component and high levels of thymidylate synthase in tumors correlate with better patient survival, indicating the potential for tailored treatment strategies based on these molecular characteristics.

Article Abstract

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 IIa 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 IIa 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.

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Source
http://dx.doi.org/10.1159/000375449DOI Listing

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