High-grade neuroendocrine carcinoma of the lung shows increased thymidylate synthase expression compared to other histotypes

J Surg Oncol. 2010 Jul 1;102(1):11-7. doi: 10.1002/jso.21576.

Abstract

Background: Thymidylate synthase (TS) expression has been reported in various tumors, including non-small-cell lung carcinoma (NSCLC), but not in high-grade neuroendocrine (HGNE) carcinoma of the lung.

Methods: We measured TS expression in surgically resected pulmonary tumors, comparing HGNE carcinomas of the lung (13 large-cell neuroendocrine carcinomas, 8 small-cell lung carcinomas) with squamous cell carcinoma and adenocarcinoma of the lung using laser-capture microdissection for tissue isolation, real-time polymerase chain reaction (PCR), and immunohistochemistry. We also measured TS mRNA expression in small-cell lung carcinoma (SCLC) and NSCLC cell lines using real-time PCR.

Results: At both mRNA and protein levels, TS expression was significantly higher in squamous cell carcinoma compared to adenocarcinoma. Moreover, TS expression was significantly higher in HGNE carcinomas of the lung compared to squamous cell carcinoma. A significant correlation was found between mRNA and protein expression. TS mRNA expression in SCLC cell lines was significantly higher than in NSCLC cell lines.

Conclusions: TS expression was higher in HGNE carcinomas of the lung than in squamous cell carcinoma, which was higher than in adenocarcinoma. This information may be useful in predicting the effects of TS-inhibiting agents in patients with NSCLC and HGNE carcinomas of the lung.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Large Cell / enzymology*
  • Carcinoma, Large Cell / genetics
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Neuroendocrine / enzymology*
  • Carcinoma, Neuroendocrine / genetics
  • Carcinoma, Neuroendocrine / pathology
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Small Cell Lung Carcinoma / enzymology
  • Small Cell Lung Carcinoma / genetics
  • Small Cell Lung Carcinoma / pathology
  • Thymidylate Synthase / genetics
  • Thymidylate Synthase / metabolism*

Substances

  • RNA, Messenger
  • Thymidylate Synthase