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Expression of the zinc-finger transcription factor Snail in adrenocortical carcinoma is associated with decreased survival.

Waldmann J, Feldmann G, Slater EP, Langer P, Buchholz M, Ramaswamy A, Saeger W, Rothmund M, Fendrich V - Br. J. Cancer (2008)

Bottom Line: Survival rates were significantly decreased in Snail-positive tumours compared to Snail-negative tumours: 10 out of 16 vs one out of eight patients succumbed to disease after a median follow up of 14.5 and 28.5 months, respectively (P=0.03).In conclusion, we describe for the first time that Snail is expressed in a large subset of ACCs.Furthermore, Snail expression is associated with decreased survival, advanced disease and higher risk of developing distant metastases.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Philipps-Universität Marburg, Marburg, Germany.

ABSTRACT
In this study, we evaluate whether Snail is expressed in adrenocortical cancer (ACC) and if its expression is related to patient outcome. One of the best known functions of the zinc-finger transcription factor Snail is to induce epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT plays a pivotal role in tumour progression and metastatic spread. Snail and E-cadherin expression were assessed by immunohistochemistry in 26 resected ACCs and real-time quantitative RT-PCR expression analysis was performed. Data were correlated with clinical outcome and in particular with overall patient survival. Seventeen of 26 (65%) ACC tumour samples expressed Snail when assessed by immunohistochemistry. Snail expression was neither detected in normal adrenocortical tissue, nor in benign adrenocortical adenomas. Expression levels were confirmed on the mRNA level by Real-Time-PCR. Survival rates were significantly decreased in Snail-positive tumours compared to Snail-negative tumours: 10 out of 16 vs one out of eight patients succumbed to disease after a median follow up of 14.5 and 28.5 months, respectively (P=0.03). Patients with Snail-expressing ACCs presented in advanced disease (11 out of 12 vs 6 out of 14, P=0.01) and tend to develop distant metastases more frequently than patients with negative staining (7 out of 11 vs two out of eight, P=0.19). In conclusion, we describe for the first time that Snail is expressed in a large subset of ACCs. Furthermore, Snail expression is associated with decreased survival, advanced disease and higher risk of developing distant metastases.

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Kaplan–Meier curve of patients with positive and negative Snail expression: Note the decreased survival of Snail-expressing ACCs. (A) Survival in 24 patients with ACC (two were excluded because of disease-unrelated death), P=0.02. (B) Survival in 20 patients with ACC (four were excluded as the follow-up was minor 12 months, two were excluded due to disease-unrelated death), P=0.01.
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fig5: Kaplan–Meier curve of patients with positive and negative Snail expression: Note the decreased survival of Snail-expressing ACCs. (A) Survival in 24 patients with ACC (two were excluded because of disease-unrelated death), P=0.02. (B) Survival in 20 patients with ACC (four were excluded as the follow-up was minor 12 months, two were excluded due to disease-unrelated death), P=0.01.

Mentions: Third, patients with Snail-expressing ACCs had a decreased survival rate (Figure 5A). Survival rates were significantly lower in Snail-positive tumours than in Snail-negative tumours (P=0.02). In addition, we analysed survival rates for patients with follow-up longer than 1 year to avoid bias because of missed metastases during shorter follow up (Figure 5B) and had very similar median follow up of 14.5 (snail positive) and 28.5 (snail negative) months in the groups. A decreased survival for patients with Snail-expressing tumours is in line with recent studies. In ovarian cancer, a high Snail mRNA expression predicted a shorter effusion-free survival in ovarian cancer (Elloul et al, 2005). In node-negative invasive ductal breast carcinomas, Snail mRNA expression correlated with disease-free and overall survival (Toyama et al, 2006). The decreased survival in our study might be either a consequence of the more advanced tumour stage and the presence of distant metastases in patients with Snail-positive tumours, or it might reflect an additional aggressiveness of the tumour cells.


Expression of the zinc-finger transcription factor Snail in adrenocortical carcinoma is associated with decreased survival.

Waldmann J, Feldmann G, Slater EP, Langer P, Buchholz M, Ramaswamy A, Saeger W, Rothmund M, Fendrich V - Br. J. Cancer (2008)

Kaplan–Meier curve of patients with positive and negative Snail expression: Note the decreased survival of Snail-expressing ACCs. (A) Survival in 24 patients with ACC (two were excluded because of disease-unrelated death), P=0.02. (B) Survival in 20 patients with ACC (four were excluded as the follow-up was minor 12 months, two were excluded due to disease-unrelated death), P=0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600683&req=5

fig5: Kaplan–Meier curve of patients with positive and negative Snail expression: Note the decreased survival of Snail-expressing ACCs. (A) Survival in 24 patients with ACC (two were excluded because of disease-unrelated death), P=0.02. (B) Survival in 20 patients with ACC (four were excluded as the follow-up was minor 12 months, two were excluded due to disease-unrelated death), P=0.01.
Mentions: Third, patients with Snail-expressing ACCs had a decreased survival rate (Figure 5A). Survival rates were significantly lower in Snail-positive tumours than in Snail-negative tumours (P=0.02). In addition, we analysed survival rates for patients with follow-up longer than 1 year to avoid bias because of missed metastases during shorter follow up (Figure 5B) and had very similar median follow up of 14.5 (snail positive) and 28.5 (snail negative) months in the groups. A decreased survival for patients with Snail-expressing tumours is in line with recent studies. In ovarian cancer, a high Snail mRNA expression predicted a shorter effusion-free survival in ovarian cancer (Elloul et al, 2005). In node-negative invasive ductal breast carcinomas, Snail mRNA expression correlated with disease-free and overall survival (Toyama et al, 2006). The decreased survival in our study might be either a consequence of the more advanced tumour stage and the presence of distant metastases in patients with Snail-positive tumours, or it might reflect an additional aggressiveness of the tumour cells.

Bottom Line: Survival rates were significantly decreased in Snail-positive tumours compared to Snail-negative tumours: 10 out of 16 vs one out of eight patients succumbed to disease after a median follow up of 14.5 and 28.5 months, respectively (P=0.03).In conclusion, we describe for the first time that Snail is expressed in a large subset of ACCs.Furthermore, Snail expression is associated with decreased survival, advanced disease and higher risk of developing distant metastases.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Philipps-Universität Marburg, Marburg, Germany.

ABSTRACT
In this study, we evaluate whether Snail is expressed in adrenocortical cancer (ACC) and if its expression is related to patient outcome. One of the best known functions of the zinc-finger transcription factor Snail is to induce epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT plays a pivotal role in tumour progression and metastatic spread. Snail and E-cadherin expression were assessed by immunohistochemistry in 26 resected ACCs and real-time quantitative RT-PCR expression analysis was performed. Data were correlated with clinical outcome and in particular with overall patient survival. Seventeen of 26 (65%) ACC tumour samples expressed Snail when assessed by immunohistochemistry. Snail expression was neither detected in normal adrenocortical tissue, nor in benign adrenocortical adenomas. Expression levels were confirmed on the mRNA level by Real-Time-PCR. Survival rates were significantly decreased in Snail-positive tumours compared to Snail-negative tumours: 10 out of 16 vs one out of eight patients succumbed to disease after a median follow up of 14.5 and 28.5 months, respectively (P=0.03). Patients with Snail-expressing ACCs presented in advanced disease (11 out of 12 vs 6 out of 14, P=0.01) and tend to develop distant metastases more frequently than patients with negative staining (7 out of 11 vs two out of eight, P=0.19). In conclusion, we describe for the first time that Snail is expressed in a large subset of ACCs. Furthermore, Snail expression is associated with decreased survival, advanced disease and higher risk of developing distant metastases.

Show MeSH
Related in: MedlinePlus