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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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Steady state Snail mRNA levels were determined by real-time RT–PCR in a subset of 10 samples.
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fig4: Steady state Snail mRNA levels were determined by real-time RT–PCR in a subset of 10 samples.

Mentions: We found that Snail is expressed in about two-third of a large series of ACCs. Snail-expressing cells were mostly found at the invasive front of the ACCs as seen in tumours induced in the skin of mice (Cano et al, 2000) and recently described by our group in neuroendocrine tumours of the ileum (Fendrich et al, 2007). At this site, tumour cells migrate into and invade the surrounding tissue either as single cells or in collective clusters and give evidence of an EMT (Zhou et al, 2004). Snail-positive invasive fronts were observed in 8 of 17 Snail-positive ACCs (Figure 1). In normal adrenocortical tissue, Snail expression was mostly absent apart from a distinct cell population close to the capsule (Figure 3C). We confirmed Snail expression levels by RT–PCR with cDNA derived from whole tumour samples (Figure 4). Expression levels correlated with data established by IHC although a discrimination of specific tumour regions as invasive areas could only have been achieved by microdissection.


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)

Steady state Snail mRNA levels were determined by real-time RT–PCR in a subset of 10 samples.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Steady state Snail mRNA levels were determined by real-time RT–PCR in a subset of 10 samples.
Mentions: We found that Snail is expressed in about two-third of a large series of ACCs. Snail-expressing cells were mostly found at the invasive front of the ACCs as seen in tumours induced in the skin of mice (Cano et al, 2000) and recently described by our group in neuroendocrine tumours of the ileum (Fendrich et al, 2007). At this site, tumour cells migrate into and invade the surrounding tissue either as single cells or in collective clusters and give evidence of an EMT (Zhou et al, 2004). Snail-positive invasive fronts were observed in 8 of 17 Snail-positive ACCs (Figure 1). In normal adrenocortical tissue, Snail expression was mostly absent apart from a distinct cell population close to the capsule (Figure 3C). We confirmed Snail expression levels by RT–PCR with cDNA derived from whole tumour samples (Figure 4). Expression levels correlated with data established by IHC although a discrimination of specific tumour regions as invasive areas could only have been achieved by microdissection.

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