Epithelial ovarian cancer is the leading cause of death among female genital malignancies. Reduced expression of the cell adhesion molecule E-cadherin was previously shown to be associated with adverse prognostic features. The role of the E-cadherin repressor Snail in ovarian cancer progression remains to be elucidated. We analysed formalin-fixed and paraffin-embedded specimens of 48 primary ovarian tumours and corresponding metastases for expression of E-cadherin and Snail by immunohistochemistry. We found a significant correlation between E-cadherin expression in primary cancers and their corresponding metastases (Po0.001). This correlation was found for Snail expression as well (Po0.001). There was a significant (P ¼ 0.008) association of reduced E-cadherin expression in primary ovarian cancer with shorter overall survival. Similarly, Snail expression in corresponding metastases (P ¼ 0.047) was associated with reduced overall survival of the patients. Additionally, the group of patients showing reduced E-cadherin and increased Snail immunoreactivity in primary tumours and corresponding metastases, respectively, had a significantly higher risk of death (P ¼ 0.002 and 0.022, respectively) when compared to the patient group with the reference expression profile E-cadherin positive and Snail negative. Taken together, the results of our study show that the E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients.

Epithelial-mesenchymal transition (EMT), a normal developmental process, is known to play a crucial role in tumor progression. Molecules involved in this process, such as the E-cadherin repressor Snail, facilitate migration and invasion of carcinoma cells. A growing number of studies addressing the expression of Snail in clinical samples have been reported and are discussed in this review. A total of 2,112 cases from 9 different tumor types were evaluated. So far, a clear picture has emerged only in some cancer types analyzed with regard to overexpression of Snail and clinical-pathological parameters. Currently, it seems that Snail may play a role in hormone-dependent carcinomas but may be of minor importance in gastrointestinal cancers for tumor dedifferentiation and the maintenance of the invasive phenotype. It should be kept in mind, however, that the threshold for Snail activity does not have to be the same in every tumor type analyzed. The recent introduction of well-characterized novel monoclonal antibodies reacting with the short-lived nuclear Snail protein may help to establish a potential clinical usefulness for this master molecule of EMT, at least for certain types of cancer.

Transcriptional E-cadherin down-regulation can be mediated by Snail, a zinc finger transcription factor. To be able to examine nuclear Snail immunoreactivity in archival human cancers, we established a monoclonal antibody against the purified human Snail protein. The specificity of the selected rat antibody Sn9H2 was demonstrated by Western blot analysis using extracts from different cell lines and by immunofluorescence and immunohistochemistry of primary tissues. Subsequently, a series of 340 adenocarcinomas of the upper gastrointestinal tract, including tumours from the oesophagus (n=154), cardia (n=102) and stomach (n=84), arranged in tissue microarrays, were examined for Snail expression and were correlated to E-cadherin expression and clinico-pathological parameters. Nuclear Snail immunoreactivity was seen in 27 tumours (7.9%) and tended to be more frequent in oesophageal adenocarcinomas (11.1%) than in cardiac (6.9%) or gastric (3.6%) carcinomas (p=0.0428). In 35% of the Snail-positive cases, E-cadherin immunoreactivity was lost. No correlation was found for nuclear Snail expression and tumour grade, Lauren's classification, WHO classification, tumour stage and tumour size. The pattern of Snail expression observed with our new hybridoma, Sn9H2, which is currently the only antibody that reacts with endogenous nuclear (active) Snail, suggests only a minor role of Snail in tumours of the upper gastrointestinal tract.

Endometrial cancer is the most common gynecologic cancer in the developed world. The cell-adhesion protein E-cadherin acts as a tumor-suppressor protein and is down-regulated by the transcription factor Snail, whose expression was shown to be associated with estrogen receptor signaling. This study aimed to investigate the expression of E-cadherin, Snail, and estrogen-receptor alpha in 87 primary tumors and 26 metastases of endometroid endometrial carcinomas. Reduced E-cadherin immunoreactivity was seen in 44.8% of the primary tumors and 65.4% of the metastases with a statistical correlation to higher tumor grade (P=0.003) only in metastatic lesions. About 28.7% of primary tumor specimens showed a positive Snail immunoreactivity that was correlated with reduced estrogen-receptor alpha expression (P=0.047). Positive Snail immunoreactivity was also seen in 53.8% of the metastases where it was correlated with higher tumor grade (P=0.003) and abnormal E-cadherin expression (P=0.003). Interestingly, a Snail expressing endometrial carcinoma-cell line showed a higher migration potential than a variant of this cell line with low levels of Snail. Taken together, our data are in line with a proposed role for Snail in endometrial tumor progression.

Spindle cell carcinoma (SpCC) is a biphasic tumor composed of squamous cell carcinoma (SCC) and a malignant spindle cell component. There is mounting evidence that SpCC is a monoclonal neoplasm originating from a stem cell giving rise to both components. We tested the hypothesis that spindle cell phenotype might be related to the cadherin-catenin complex, which forms adherens junctions between cells. We analyzed the immunohistochemical expression of E- and N-cadherin, alpha-, beta- and gamma-catenin, and Snail-1, a transcription repressor of E-cadherin, in 30 cases of SpCC, and 30 cases of SCC of the head and neck. In SpCC, cadherin and catenin expression was similar in the SCC component, whereas in the spindle cell component, loss of E-cadherin and neo-expression of N-cadherin was found in 19 cases, loss of cadherins in seven, and their co-expression in four cases. Catenin expression were altered in 18 SpCCs. Snail-1 was found in 19 SpCC cases. In SCC, E-cadherin and catenins were expressed in all cases, and N-cadherin focally in five cases. Snail-1 was observed in the stroma. To summarize, in SpCC, there is an altered expression of the cadherin-catenin complex, associated with morphological transition from epithelial to spindle cell phenotype. These features are reminiscent of epithelial-mesenchymal transition (EMT). Our study thus indicates that EMT might play an important role in the pathogenesis of SpCC. This conclusion is further supported by our finding of Snail-1 expression, a potent inducer of EMT, in more than half SpCC cases.