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

Galván JA, Astudillo A, Vallina A, Crespo G, Folgueras MV, González MV - BMC Cancer (2014)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Surgery Department, Faculty of Medicine and Health Sciences, University of Oviedo, c/ Julián Clavería s/n, 33006 Oviedo, Asturias, Spain. gonzalezvictoria@uniovi.es.

ABSTRACT

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.

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Related in: MedlinePlus

Cumulative Kaplan–Meier survival curves stratified of patients diagnosed with TC, according to E-cadherin/β-catenin complex.
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Fig6: Cumulative Kaplan–Meier survival curves stratified of patients diagnosed with TC, according to E-cadherin/β-catenin complex.

Mentions: Typical carcinoid (TC) tumors have better prognosis than other pulmonary NETs. However, some of these patients follow an unfavourable clinical course, unpredictable from the available clinicopathological features, including lymph node status. In our series, only 1/5 patients with an unfavourable course had affected nodes. With the aim of finding some molecular factors that could help in the identification of this subgroup, we performed a survival analysis on the TC series. The mean follow-up time for this group was 106 months (range 14-242 months) and 92.4% had tumour free lymph nodes. There was a difference in ten year survival rates when these patients were stratified by E-cadherin/β-catenin complex integrity (94% complex preserved vs 56% complex altered p = 0.03) (Figure 6). This result could provide tools that assist the clinician to identify patients with TC of poor prognosis.Figure 6


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

Galván JA, Astudillo A, Vallina A, Crespo G, Folgueras MV, González MV - BMC Cancer (2014)

Cumulative Kaplan–Meier survival curves stratified of patients diagnosed with TC, according to E-cadherin/β-catenin complex.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4256901&req=5

Fig6: Cumulative Kaplan–Meier survival curves stratified of patients diagnosed with TC, according to E-cadherin/β-catenin complex.
Mentions: Typical carcinoid (TC) tumors have better prognosis than other pulmonary NETs. However, some of these patients follow an unfavourable clinical course, unpredictable from the available clinicopathological features, including lymph node status. In our series, only 1/5 patients with an unfavourable course had affected nodes. With the aim of finding some molecular factors that could help in the identification of this subgroup, we performed a survival analysis on the TC series. The mean follow-up time for this group was 106 months (range 14-242 months) and 92.4% had tumour free lymph nodes. There was a difference in ten year survival rates when these patients were stratified by E-cadherin/β-catenin complex integrity (94% complex preserved vs 56% complex altered p = 0.03) (Figure 6). This result could provide tools that assist the clinician to identify patients with TC of poor prognosis.Figure 6

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Surgery Department, Faculty of Medicine and Health Sciences, University of Oviedo, c/ Julián Clavería s/n, 33006 Oviedo, Asturias, Spain. gonzalezvictoria@uniovi.es.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus