Abstract
E-cadherin has been identified as a tumor suppressor in many types of carcinoma. However, some studies recently suggested that the role and expression of E-cadherin might be more complex and diverse. In the present study, we evaluated the prognostic value of E-cadherin expression with reference to levels in membranes and cytoplasm, and the membrane/cytoplasm ratio, in hepatocellular carcinomas (HCCs) after curative hepatectomy. The expression of E-cadherin was assessed by immunohistochemistry in HCC tissue microarrays from 125 patients, and its prognostic values and other clinicopathlogical data were retrospectively analyzed. Patients were followed for a median period of 43.7 months (range 1 to 126 months). Univariate analysis demonstrated that a high membrane/cytoplasm (M/C) ratio of E-cadherin expression was associated with poor overall survival (OS) (P =0.001) and shorter time to recurrence (TTR) (P =0.038), as well as tumor size, intrahepatic metastasis, and TNM stage. In contrast, neither membrane nor cytoplasmic expression of E-cadherin was related with OS and TTR. Furthermore, multivariate analysis confirmed the M/C ratio to be an independent predictor of OS (P =0.031). ?2 tests additionally showed that the M/C ratio of E-cadherin expression was related with early stage recurrence (P =0.012), rather than later stage recurrence. The M/C ratio of E-cadherin expression is a strong predictor of postoperative survival and is associated with early stage recurrence in patients with HCC.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common aggressive malignant tumor in the world
We evaluated the prognostic value of E-cadherin expression with reference to levels in membranes and cytoplasm, and the membrane/cytoplasm ratio, in hepatocellular carcinomas (HCCs) after curative hepatectomy
In the present study of 125 diagnosed HCC with curative hepatectomy, we found that high E-cadherin membrane/cytoplasm ratio, but neither membrane nor cytoplasm E-cadherin expression, associating with large tumor size and intrahepatic metastasis, was an efficient poor prognosis predictive marker
Summary
Hepatocellular carcinoma (HCC) is the sixth most common aggressive malignant tumor in the world. Surgical resection is the preferred standard treatment for patients with resectable HCC, but high postoperative recurrence, especially early recurrence, and metastasis rate remain the major obstacles that influence long-term survival (Tang et al, 2004). Improving our understanding of the postoperation metastasis and recurrence mechanisms, and identifying recurrence markers of HCC is essential for improving clinical outcomes in treatment. E-cadherin is a 120kDa calcium-dependent transmembrane glycoprotein widely expressed at adhesion junctions in most normal epithelial tissues and well-differentiated cancer cells (Bussemakers et al, 1993). E-cadherin was identified as a tumor suppressor in many types of carcinoma (Ross et al, 1995; Cespedes et al, 2010; Montserrat et al, 2011)
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