Reduced expression of plakoglobin indicates an unfavorable prognosis in subsets of patients with non-small-cell lung cancer.
OBJECTIVE
Plakoglobin is thought to play a key role in cadherin-mediated epithelial cell adhesion, because it is a common component of desmosomal and nondesmosomal adherens junctions. Because loss of homotypic cell adhesion is an important early step in invasion and metastasis of solid tumors, we evaluated the frequency and prognostic significance of a deficient expression of plakoglobin in human lung cancer.


METHODS
At primary surgery, representative specimens of the primary tumor were obtained from 96 consecutive patients with completely resected non-small-cell lung carcinoma (NSCLC) without overt distant metastases. Cryostat sections of these specimens and metastatic lymph nodes were stained with monoclonal antibody (mAb) PG 5.1 against plakoglobin, using an immunoperoxidase technique. Patients were monitored for a median of 39 months (range, 12 to 56) after surgery.


RESULTS
Absent or severely reduced expression of plakoglobin (ie, < 30% positive tumor cells) was observed in 39 patients (40.6%). There was no significant correlation to established risk factors, such as the histology, extension, and histologic grade of the primary tumor and metastatic lymph node involvement, or expression of alpha-catenin. Expression of plakoglobin in lymph node metastases ranged from 0% to greater than 60% positive tumor cells. Deficient plakoglobin expression on the primary tumor was significantly correlated to a shortened disease-free and overall survival in patients with adenocarcinomas, pT1-2 tumors, or negative lymph nodes (pN0). In patients with pT1-2 tumors, the independence of this prognostic influence from established risk factors was demonstrated by Cox regression analyses (disease-free survival, P = .002; overall survival, P = .038).


CONCLUSIONS
Deficient expression of plakoglobin appears to be an important event in the progression of NSCLC.
Pantel
K
K
Institut für Immunologie, Ludwig-Maximilians-Universität, München, Germany. Pantel@ifi.med.uni-muenchen.de
Passlick
B
B
Vogt
J
J
Stosiek
P
P
Angstwurm
M
M
Seen-Hibler
R
R
Häussinger
K
K
Thetter
O
O
Izbicki
J R
JR
Riethmüller
G
G
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000172:deficiency / Q000235:genetics; D051180:Desmoplakins; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016019:Survival Analysis; D051185:gamma Catenin
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D051185:gamma Catenin