Expression of the E-cadherin/catenin (alpha-, beta-, and gamma-) complex correlates with the macroscopic appearance of early gastric cancer.
E-cadherin and its associated cytoplasmic proteins, alpha-, beta-, and gamma-catenins, play an essential role in the control of epithelial differentiation. We have previously shown that loss or down-regulation of E-cadherin/catenin correlates with poor survival in advanced gastric adenocarcinoma. The aim of this study was to assess the expression of E-cadherin and catenins in early gastric cancers (EGCs). Immunohistochemical staining for E-cadherin and alpha-, beta-, and gamma-catenins was performed on 41 paraffin-embedded gastrectomy specimens of EGC using an indirect immunoperoxidase technique. The pattern of expression and cellular localization of the E-cadherin/catenin complex in tumour cells were correlated with the macroscopic appearance of the tumour according to the Japanese Endoscopic Society classification. The tumours were classified as follows: three type I (protruding) and 38 type II (superficial), of which ten were type IIa (elevated), one was type IIb (flat), and 27 were type IIc (depressed). E-cadherin and alpha-, beta-, and gamma-catenins were expressed at the cell-cell junctions in normal mucosa. Forty out of 41 tumours showed abnormal expression (loss of membranous immunoreactivity and/or nuclear staining) of at least one component of the E-cadherin catenin complex. Loss of E-cadherin immunoreactivity was more frequently seen in type IIb (1/1, 100%) and type IIc (27/27, 100%) than in type I (1/3, 33%) and type IIa (1/10, 10%) (p<0.01). Abnormal expression of E-cadherin and alpha-catenin was more frequently seen in diffuse-type than in intestinal type tumours (p<0.05). Abnormal immunoreactivity of beta- and gamma-catenin, including nuclear localization, was observed in 34% and 7.3% of tumours, respectively, but there was no significant correlation with tumour type or endoscopic appearance. In conclusion, abnormal expression of the E-cadherin/catenin complex occurs in EGC and seems to correlate with macroscopic appearances.
Ohene-Abuakwa
Y
Y
Division of Histopathology, Department of Pathology and Microbiology, University of Bristol, Bristol Royal Infirmary, Bristol, UK.
Noda
M
M
Perenyi
M
M
Kobayashi
N
N
Kashima
K
K
Hattori
T
T
Pignatelli
M
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051180:Desmoplakins; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
D014408:Biomarkers, Tumor; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin