title: Expression analysis of genes involved in DNA repair or synthesis in mixed neuroendocrine/nonneuroendocrine carcinomas.
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.
authors: Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, Italy.
authors: Marco
authors: M
authors: Volante
authors: Valentina
authors: V
authors: Monica
authors: Nadia
authors: N
authors: Birocco
authors: Maria Pia
authors: MP
authors: Brizzi
authors: Simone
authors: S
authors: Busso
authors: Lorenzo
authors: L
authors: Daniele
authors: Stefano
authors: S
authors: La Rosa
authors: Luisella
authors: L
authors: Righi
authors: Anna
authors: A
authors: Sapino
authors: Alfredo
authors: A
authors: Berruti
authors: Giorgio V
authors: GV
authors: Scagliotti
authors: Mauro
authors: M
authors: Papotti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016019:Survival Analysis; D014565:Urogenital Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology