EXPRESSION OF PLAKOGLOBIN IN LUNG-CANCER - FREQUENCY AND PROGNOSTIC-SIGNIFICANCE

Loss of homotypic cell adhesion is an important prerequisite for invas ion and metastasis of epithelial tumor cells. The function of E-cadher in, which mediates epithelial cell-cell adhesion, is regulated by a co mplex of proteins bound to its cytoplasmic tail, including a-, b-, g-c atenins and plakoglobin (PG). The present study was designed to assess whether downregulation of plakoglobin expression occurs in human non- small cell lung carcinomas (NSCLC) and whether this change is associat ed with an unfavorable prognosis. Using immunohistochemistry with mono clonal antibody (mAb) PG 5.1 to PG, absence or severely reduced expres sion of PG (i.e., less than 30% of positive tumor cells) was observed in 39 of 97 patients (40.2%) with completely resected primary NSCLC (s tages T1-3, N1-2, MO). There was no significant correlation to any of the analyzed clinicopathologic factors such as histologic type, grade or size of the primary tumor, and lymph node involvement. After a medi an observation period of 39 months (12-56 mo.), univariate Kaplan-Meie r analysis showed that patients with PG-deficient primaries tended to have a shortened disease-free survival(p=0.06). This correlation was s tatistically significant in patients with adenocarcinomas (p=0.010), l ocally restricted primary tumors (pT 1/2, p = 0.017), and negative lym ph nodes (pNO, p = 0.036). Analysis of the overall survival in these s ubgroups also revealed significant associations between deficient pc e xpression and poor outcome (p less than or equal to 0.036). Multivaria te analysis was performed for the largest subgroup of patients with pT 1/2 tumors (n = 66), demonstrating that PG expression was a strong, in dependent predictor of tumor relapse (p = 0.002). Thus, deficient expr ession of PG is a frequent, early event in the progression of NSCLC, w hich appears to predict an unfavorable prognosis in patients at earlie r stages of their disease.