Downregulation and abnormal expression of E-cadherin and beta-catenin in nasopharyngeal carcinoma: close association with advanced disease stage and lymph node metastasis

Hum Pathol. 1999 Apr;30(4):458-66. doi: 10.1016/s0046-8177(99)90123-5.


Nasopharyngeal carcinoma (NPC) is predominantly of the undifferentiated histological subtype. Histological differentiation is of limited prognostic significance in NPC. Recent studies have suggested that downregulation of the cadherin-catenin cell adhesion complex may play a crucial role in the initial stage of cancer invasion and metastasis and is associated with poor prognosis in human cancers. Expression of E-cadherin has not been reported previously in NPC, and its prognostic value in NPC is unknown. The purpose of this study was to examine the expression pattern of E-cadherin and its associated partner, beta-catenin, in NPC and their possible applications as prognostic markers to predict the clinical outcome of NPC. Expression of the E-cadherin and beta-catenin was examined by immunohistochemical methods in 74 cases of primary NPC and 17 of their corresponding lymph node metastases. Normal nasopharyngeal epithelium showed strong and homogeneous immunocytochemical staining of E-cadherin and beta-catenin at the cell membranes and intercellular junctions. In contrast, primary NPC showed variable and heterogeneous staining patterns of E-cadherin and beta-catenin. Loss of membranous E-cadherin expression was significantly associated with advanced stages of diseases (P<.001). Eighty percent to ninety percent of NPC in stages IV and V (Ho's staging), respectively, showed a reduced (<35%) membranous staining of E-cadherin compared with normal nasopharyngeal epithelium. Expression of beta-catenin also was downregulated in advanced NPC. Ninety percent to one hundred percent of NPC in stages IV and V (Ho's staging) expressed a reduction (<35%) of imnmunocytochemical staining of beta-catenin. The expression pattern of beta-catenin staining was strongly associated with the expression of E-cadherin (P<.001). Unlike E-cadherin, nuclear staining of beta-catenin expression was observed in some of the primary NPC and lymph node metastasis. Reduced expression of E-cadherin and beta-catenin expression was associated with a shorter survival of NPC patients (P<.001). In advanced NPC patients (stages IV and V), a significant difference in survival was observed in tumors with higher or lower levels of E-cadherin expression (P=.0224, log-rank test). These observations suggests that expression of E-cadherin and beta-catenin may have prognostic values in NPC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cadherins / biosynthesis*
  • Carcinoma / metabolism*
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Cytoskeletal Proteins / biosynthesis*
  • Down-Regulation
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / metabolism
  • Lymphatic Metastasis
  • Middle Aged
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharynx / metabolism
  • Neoplasm Staging
  • Survival Rate
  • Trans-Activators*
  • beta Catenin


  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin