Prognostic and diagnostic value of epithelial to mesenchymal transition markers in pulmonary neuroendocrine tumors

BMC Cancer

Jose A Galván³  Aurora Astudillo²  Aitana Vallina³  Guillermo Crespo¹  Maria Victoria Folgueras²  Maria Victoria González⁴ 

[1] Oncology Department, University Hospital of Burgos, c/ Islas Baleares, 3, 09006 Burgos, Spain

[2] Pathology Department, University Central Hospital of Asturias, 33006 Oviedo, Spain

[3] Tumor Bank Laboratory, University Institute of Oncology Principality of Asturias, CajAstur Welfare Project (IUOPA, c/ Celestino Villamil s/n, 33006 Oviedo, Asturias, Spain

[4] University Institute of Oncology Principality of Asturias, CajAstur Welfare Project (IUOPA), c/ Julián Clavería s/n, 33006 Oviedo, Asturias, Spain

关键词: Foxc2;    Snail;    β-catenin;    E-cadherin;    Epithelial-Mesenchymal transition;    Pulmonary neuroendocrine tumors;   

Others  :  1118065
DOI  :  10.1186/1471-2407-14-855

 received in 2013-11-11, accepted in 2014-11-07,  发布年份 2014

【 摘 要 】

Background

Pulmonary neuroendocrine tumors (Pulmonary NETs) include a wide spectrum of tumors, from the low-grade typical carcinoid (TC) and the intermediate-grade atypical carcinoid (AC), to the high-grade large-cell neuroendocrine carcinoma (LCNEC) and the small-cell carcinoma (SCLC). Epithelial Mesenchymal Transition (EMT) is a process initially recognised during several critical stages of embryonic development, which has more recently been implicated in promoting carcinoma invasion and metastasis. The initial stage of the EMT process begins with the deregulation of adhesion molecules, such as E-cadherin, due to transcriptional repression carried out by factors such as Snail family members, Twist and Foxc2.

Methods

Immunohistochemistry for EMT markers and E-cadherin/ β-catenin complex in 134 patients with pulmonary NETs between 1990 – 2009. Analysis of potential associations with clinicopathological variables and survival.

Results

Pulmonary NETs of high malignant potential (LCNEC and SCLC) had reduced expression of the adhesion molecules and high level expression of transcriptional repressors (Snail1, Snail2, Twist and Foxc2). Snail high expression levels and the loss of E-cadherin/β-catenin complex integrity had the strongest negative effect on the five-year survival rates. E-cadherin/β-catenin complex integrity loss independently predicted lymph node involvement and helped in Atypical Carcinoid (AC) vs Typical Carcinoid (TC) differential diagnosis. Importantly, among the TC group, the loss of E-cadherin/β-catenin complex integrity identified patients with an adverse clinical course despite favourable clinicopathological features.

Conclusion

The immunohistochemical determination of E-cadherin/β-catenin complex integrity loss and EMT markers in the clinical setting might be a potential useful diagnostic and prognostic tool especially among the TC patients.

【 授权许可】

   
2014 Galván et al.; licensee BioMed Central Ltd.

【 图 表 】

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