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http://purl.uniprot.org/citations/18281538http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18281538http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

The predictive role of the quantification of thymidylate synthase (TS) in tumors treated with antifolate drugs, such as 5-fluorouracil (5-FU), has been extensively reported in a variety of human tumors. Neuroendocrine tumors (NET) represent potential targets of antifolate agents, but no data on TS expression level in these tumors are currently available.

Experimental design

A series of 116 NETs were collected, including 58 gastroenteropancreatic (GEP) and 58 lung NETs. In 24 well-differentiated GEP neuroendocrine carcinomas (WD-NEC), a 5-FU-based treatment was given. Total RNA was extracted from microdissected paraffin blocks. TS mRNA quantification was done by real-time PCR, whereas protein expression was evaluated by immunohistochemistry.

Results

By means of both quantification by real-time PCR and immunohistochemistry, a higher TS expression in pulmonary small cell lung cancer and large cell NEC compared with typical and atypical carcinoids was observed (P < 0.01). Similarly, in GEP tumors, a higher TS expression in poorly differentiated carcinomas than both WD-NEC and benign tumors (P < 0.01) was found. In patients with WD-NEC treated with 5-FU, high TS mRNA levels were associated with shorter time to progression (P = 0.002) and overall survival (P = 0.04). This negative prognostic role was confirmed in multivariate analysis adjusting for major prognostic variables (P = 0.01). No association between TS mRNA and survival was observed in WD-NEC patients not receiving 5-FU.

Conclusions

This study, for the first time, (a) reports the differential TS expression in the spectrum of NETs and (b) indicates TS as a possible predictive marker of treatment efficacy in WD-NEC patients treated with 5-FU."xsd:string
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http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/author"Ferrero A."xsd:string
http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/author"Papotti M."xsd:string
http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/author"Volante M."xsd:string
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http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/author"Righi L."xsd:string
http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/author"Dogliotti L."xsd:string
http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/author"Scagliotti G.V."xsd:string
http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/author"Rapa I."xsd:string
http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/author"Ceppi P."xsd:string
http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/author"Rosas R."xsd:string
http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/name"Clin Cancer Res"xsd:string
http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/pages"1059-1064"xsd:string
http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/title"Thymidylate synthase expression in gastroenteropancreatic and pulmonary neuroendocrine tumors."xsd:string
http://purl.uniprot.org/citations/18281538http://purl.uniprot.org/core/volume"14"xsd:string
http://purl.uniprot.org/citations/18281538http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18281538
http://purl.uniprot.org/citations/18281538http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18281538
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