TY - JOUR
T1 - Cadherins and catenins in clival chordomas
T2 - Correlation of expression with tumor aggressiveness
AU - Triana, Aymara
AU - Sen, Chandranath
AU - Wolfe, David
AU - Hazan, Rachel
PY - 2005/11
Y1 - 2005/11
N2 - The local invasiveness and occasional rapid growth of chordomas, despite optimal treatment, highlight the need to develop ways to predict their biologic behavior. Alterations in adhesion proteins have been shown to participate in proliferation, invasiveness, and metastasis in epithelial tumors. We therefore analyzed the expression of E-cadherin, N-cadherin, as well as their cytosolic binding proteins α-catenin, β-catenin, and γ-catenin, in 51 paraffin archived and 17 cryopreserved chordoma specimens. In the majority of chordomas, E-cadherin and N-cadherin expression was inversely correlated, whereas β-catenin and γ-catenin expression was directly correlated. By multivariate analysis, N-cadherin up-regulation correlated with a diminished recurrence-free survival, and E-cadherin down-regulation strongly correlated with increased probabilities of death as determined by the Kaplan-Meier log-rank test. There was a 3.28-fold increased probability of having a tumor recurrence and a 10.98-fold increased probability of dying when, respectively, N-cadherin was up-regulated and E-cadherin down-regulated. These results suggest that changes in the relative expression of the cadherin-catenin complex reflect chordoma aggressiveness; and that decreased expression of E-cadherin and increased expression of N-cadherin may underlie the transition from a less to a more aggressive tumor phenotype.
AB - The local invasiveness and occasional rapid growth of chordomas, despite optimal treatment, highlight the need to develop ways to predict their biologic behavior. Alterations in adhesion proteins have been shown to participate in proliferation, invasiveness, and metastasis in epithelial tumors. We therefore analyzed the expression of E-cadherin, N-cadherin, as well as their cytosolic binding proteins α-catenin, β-catenin, and γ-catenin, in 51 paraffin archived and 17 cryopreserved chordoma specimens. In the majority of chordomas, E-cadherin and N-cadherin expression was inversely correlated, whereas β-catenin and γ-catenin expression was directly correlated. By multivariate analysis, N-cadherin up-regulation correlated with a diminished recurrence-free survival, and E-cadherin down-regulation strongly correlated with increased probabilities of death as determined by the Kaplan-Meier log-rank test. There was a 3.28-fold increased probability of having a tumor recurrence and a 10.98-fold increased probability of dying when, respectively, N-cadherin was up-regulated and E-cadherin down-regulated. These results suggest that changes in the relative expression of the cadherin-catenin complex reflect chordoma aggressiveness; and that decreased expression of E-cadherin and increased expression of N-cadherin may underlie the transition from a less to a more aggressive tumor phenotype.
KW - Aggressiveness
KW - Cadherin
KW - Catenins
KW - Chordoma
KW - Expression
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U2 - 10.1097/01.pas.0000180447.25141.a4
DO - 10.1097/01.pas.0000180447.25141.a4
M3 - Article
C2 - 16224208
AN - SCOPUS:27244456520
SN - 0147-5185
VL - 29
SP - 1422
EP - 1434
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 11
ER -