Clinical significance of E-cadherin as a prognostic marker in thyroid carcinomas.

Abstract

The aim of this study was to evaluate the expression of E-cadherin as a potential marker for the prognosis of thyroid carcinomas. In normal thyroid (n = 8), the expression of E-cadherin messenger ribonucleic acid levels was uniformly high and seemed to be restricted to thyrocytes. Steady-state messenger ribonucleic acid levels and immunostaining were both completely lost in undifferentiated thyroid carcinomas (n = 7) and were variably reduced in differentiated thyroid carcinomas (n = 44). In a follow-up study during a mean of 4.5 +/- 1.4 yr, E-cadherin messenger ribonucleic acid and immunohistochemical expression were compared with the initial clinicopathological parameters and with locoregional recurrence and the development of nodal or distant metastases in differentiated thyroid carcinomas. Immunohistochemical expression of E-cadherin was greatly reduced with the progression to primary tumor stage 4 (pT4) tumors. In parallel, patients with pT4 tumors had a higher rate of locoregional tumor recurrence and distant metastasis than did the group of patients with pT1-3 tumors. In 5 of 29 patients with pT4 tumors, positive E-cadherin staining of more than 30% of the cells was detected. None of these patients showed signs of a regional recurrence or distant metastases during an observation period of 4.3 +/- 1.1 yr. In 13 patients with E-cadherin-positive tumors, none developed new distant metastases which was in contrast to 7 of the group of 31 patients with less than 30% E-cadherin-positive cells. Thus, E-cadherin expression seems to be associated with the dedifferentiation, progression, and metastatic spread of thyroid carcinomas and may be a useful marker for the prognosis of these tumors.

E-cadherin expression is more associated with histopathological type of thyroid cancer than with the metastatic potential of tumors

“…On the other hand, Naito et al (2001) found that E-CAD expression was preserved significantly less often in papillary cancer with lymph node metastasis than in node-negative cases, but E-CAD expression did not correlate significantly with other clinical factors including tumor diameter, extracapsular tumor extension or histological differentiation [12]. These and our results are thus in contrast to those reported by Brabant, von Wasilewski, Scheumman, Walgenbach and Batistatou [8][9][10][11]31]. Brabant et al (1993) observed lower or undetectable E-CAD immunoreactivity in tumors presenting lymph node metastases, distant metastases or local recurrence [8].…”

“…Others accept a well defined limit of the percentage of positively stained cells to distinguish reduction of E-CAD expression. Scheumman et al (1995) set such a limit at 30% of positive cells in tumor [9]. Naito et al (2001) treated E-CAD expression as preserved if more than 50% of cells were stained, and Kato et al (2002) raised that limit to 70% of tumor cells [12,18].…”

“…Evaluation of E-CAD in the thyroid has focused on the relation of E-CAD expression to size of tumor, lymph nodules involvement or presence of metastasis, but the reported results are not consistent [8][9][10][11][12][13][14][15]. In only some of those reports has the expression of E-CAD been evaluated in relation to histologic subtype of papillary thyroid cancer or the pattern of local invasion in follicular cancers (minimally invasive versus widely invasive) [16][17][18][19][20][21].…”

Tyrosine kinase receptor RON in human pancreatic cancer

“…6 EMT has also been implicated in tumor progression and metastasis formation and is associated with a worse clinical prognosis. [7][8][9] In epithelial cells, activation of RON leads to increased cell invasion and migration, properties associated with EMT. Although RON has been studied in breast, colon, and ovarian cancers, where it has been shown to be overexpressed, [10][11][12] there are no reports on the role of RON in pancreatic cancer.…”

NATH, a novel gene overexpressed in papillary thyroid carcinomas

“…Increased expression of fibronectin (Ryu et al, 1997;Takano et al, 1998) and cathepsin B (Shuja et al, 1999) is also associated with the PTC phenotype. The cyclindependent kinase inhibitor p27/kip1 protein (Resnick et al, 1998) and the adhesion molecule E-cadherin (Scheumman et al, 1995;von Wasielewski et al, 1997) are examples of genes down-regulated in PTC versus non-neoplastic thyroid tissue. A recent microarray study, using oligonucleotides representing more than 12 000 genes, showed highly consistent gene expression profiles in PTC (Huang et al, 2001).…”