Analysis of 320 gastroenteropancreatic neuroendocrine tumors identifies TS expression as independent biomarker for survival

Autor: Soyeon Ahn, Jihun Kim, Steven N. Hochwald, Min Chen, Frederic J. Kaye, Kyungah Maeng, Woo Ho Kim, Carmen J. Allegra, Maria Zajac-Kaye, Hye Seung Lee
Rok vydání: 2013
Předmět:
Zdroj: International journal of cancer. 135(1)
ISSN: 1097-0215
Popis: Thymidylate synthase (TS), a critical enzyme for DNA synthesis and repair, is both a potential tumor prognostic biomarker as well as a tumorigenic oncogene in animal models. We have now studied the clinical implications of TS expression in gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and compared these results to other cell cycle biomarker genes. Protein tissue arrays were used to study TS, Ki-67, Rb, pRb, E2F1, p18, p21, p27 and menin expression in 320 human GEP-NETs samples. Immunohistochemical expression was correlated with univariate and multivariate predictors of survival utilizing Kaplan Meier and Cox proportional hazards models. Real time RT-PCR was used to validate these findings. We found that 78 of 320 GEP-NETs (24.4%) expressed TS. NETs arising in the colon, stomach and pancreas showed the highest expression of TS (47.4%, 42.6% and 37.3%, respectively), whereas NETs of the appendix, rectum and duodenum displayed low TS expression (3.3%, 12.9% and 15.4%, respectively). TS expression in GEP-NETs was associated with poorly differentiated endocrine carcinoma, angiolymphatic invasion, lymph node metastasis and distant metastasis (p
Databáze: OpenAIRE