Abstract 1487: Evaluation of the relationship between e-cadherin expression and proliferative activity at the invasive front of esophageal squamous cell carcinoma.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Introduction Esophageal squamous cell carcinoma (ESCC) has a poor prognosis mainly because it is usually in an advanced stage at the time of diagnosis. The epithelium-mesenchyme transition (EMT), when epithelial cells loss their original characteristics and acquire mesenchymal phenotype, is indicated first by the loss of E-cadherin expression. The EMT is considered the main event in tumor progression and metastasis. In vitro studies have demonstrated that e-cadherin downregulation can lead to cell proliferation. This finding has not been evaluated in human tumors. This study aimed to elucidate whether tumor cells that have undergone EMT at the invasive front of the ESCC are in proliferative state. Material and Methods Samples of 58 ESCC cases were double stained by immunohistochemistry (IHQ) for E-cadherin (BD Bioscience) and Ki67 (ROCHE) antibodies using the Automated System Ventana BenchMark XT (ROCHE). IHC analysis was performed using Aperio ScanScope XT (APERIO) with the Algorithm ColorDeconvolution. In each case E-cadherin and Ki67 expression were evaluated in the tumor core and at the invasive front, separately. Positivity was divided into strong, moderate and weak positive according to intensity staining. For each case a score was given based on the formula with the percentages of each positivity group [Score = 1x (% Weak) + 2x (% Moderate) + 3x (% Strong)]. Results and Discussion Analysis of the IHQ double-stain for E-cadherin showed that 51 (87.9%) cases had a high expression at the tumor core when compared with invasive front and in 7 (12.1%) cases were found high expression at the invasion front (p<0,001). The median values for E-cadherin double-stain scores were 184.2 and 163.0 at invasive front and tumor core, respectively (p<0.001). Analyses of the Ki67 double-stain showed that 19 (32.7%) cases showed a high expression at tumor core and 39 (67.3%) cases showed a high expression at the invasive front (p<0,001). Proliferation rates, represented by Ki67 expression, showed median values of 8.1 and 6.8 at the invasive front and tumor core, respectively (p=0.052). Spearman correlation between the IHQ double and single-stain was moderately positive (p <0.001). Conclusion Tumor cells at the invasive front showed an increased proliferation rate as they lose the E-cadherin expression and at the tumor core showed an higher expression of E-cadherin and a lower expression of Ki67. However, some cases showed a different behavior with a higher expression of E-cadherin at the invasive front and a elevated rate proliferation at tumor core. A more complex mechanism in the dynamics of E-cadherin and Ki67 expressions could be acting during EMT. Further studies are necessary to the better understanding of the complexity of this mechanism. Citation Format: Juliano Jampietro, Yukie Sato-Kuwabara, Jose Humberto H.T.G. Fregnani, Felipe Coimbra, Claudia Malheiros Coutinho Camillo, Fernando Augusto Soares. Evaluation of the relationship between e-cadherin expression and proliferative activity at the invasive front of esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1487. doi:10.1158/1538-7445.AM2013-1487