E-cadherin and alpha-catenin expression in human esophageal cancer.
Intercellular adhesion of the epithelial tissue is mainly regulated by the E-cadherin (E-cad) molecule. alpha-Catenin (alpha-cat) is one of the E-cad-associated cytoplasmic proteins that forms a linkage to the cytoskeleton and regulates E-cad function. To investigate the mechanism of dysfunction in cell-cell adhesion in cancerous tissues, we examined E-cad and alpha-cat expression by immunohistochemical staining on 46 human esophageal cancers using our specific monoclonal antibodies. By grading of E-cad and alpha-cat expression as uniformly positive (+), heterogeneous (+/-), or uniformly negative (-), the 46 tumors could be classified into 9 (20%) E-cad(+)/alpha-cat(+), 15 (33%) E-cad(+/-)/alpha-cat(+/-), 21 (46%) E-cad(+/-)/alpha-cat(-), and 1 (2%) E-cad(-)/alpha-cat(-). Twenty-five (54%) of the 46 tumors showed a similar expression of both molecules, while the other 21 tumors (46%) showed E-cad(+/-)/alpha-cat(-). Thus, although the expression of alpha-cat was significantly correlated with that of E-cad, in some tumors the reduction of alpha-cat was greater. Regarding the clinicopathological features, the reduction of alpha-cat expression, as well as that of E-cad, was significantly associated with tumor dedifferentiation, infiltrative growth, and lymph node metastasis (P < 0.01). Furthermore, the frequency of lymph node metastasis in E-cad(+/-)/alpha-cat(-) tumors was significantly higher (90%) than in E-cad(+)/alpha-cat(+) tumors (22%) (P < 0.01) or in E-cad(+/-)/alpha-cat(+/-) tumors (47%) (P < 0.05). These results suggest that not only E-cad but also alpha-cat are important regulators of intercellular adhesion and that alpha-cat is also involved in invasion and metastasis. In particular, reduction of alpha-cat expression is more correlated with invasive phenotype and lymph node metastasis than E-cad expression in human esophageal cancer.
Kadowaki
T
T
Department of Surgery II, Osaka University Medical School, Japan.
Shiozaki
H
H
Inoue
M
M
Tamura
S
S
Oka
H
H
Doki
Y
Y
Iihara
K
K
Matsui
S
S
Iwazawa
T
T
Nagafuchi
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000032:analysis*; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D051178:alpha Catenin
C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051178:alpha Catenin