Clinicopathological significance of CADM4 expression, and its correlation with expression of E-cadherin and Ki-67 in colorectal adenocarcinomas.
OBJECTIVE
Cell adhesion molecule 4 (CADM4) is a novel tumour suppressor. The purpose of this study was to investigate the correlation between its expression and the expression of E-cadherin and Ki-67 in colorectal adenocarcinomas, as well as its effect on patient survival.


METHODS
We evaluated CADM4 expression in tissue microarrays of 513 colorectal adenocarcinomas by immunohistochemistry.


RESULTS
CADM4 was highly expressed in 210 of the 513 colorectal adenocarcinomas; expression was reduced in 185 cases and absent in the remaining cases. Loss of CADM4 expression was correlated with larger tumour size (6.2±2.1 cm vs 5.3±2.0 cm, p<0.001), mucinous tumour type (61.5% vs 20.9%, p<0.001), lymph node metastasis (31.4% vs 20.9%, p=0.022), higher Dukes stage (25.5% vs 19.6%, p=0.044), poorer differentiation (38.5% vs 18.8%, p<0.001), absence of E-cadherin expression (28.5% vs 16.0%, p=0.007) and presence of Ki-67 expression (27.3% vs 12.3%, p<0.001). In univariable Cox regression analysis, absence of CADM4 expression was associated with poorer overall survival (HR 0.712; 95% CI 0.512 to 0.989, p=0.042) and disease-free survival (HR 0.732; 95% CI 0.546 to 0.981, p=0.037). In multivariate analysis with the Cox proportional hazards model, CADM4 expression was not an independent prognostic factor of overall survival (HR 0.726; 95% CI 0.516 to 1.021, p=0.066) and disease-free survival (HR 0.762; 95% CI 0.563 to 1.033, p=0.080).


CONCLUSIONS
Loss of CADM4 expression is relatively frequent in colorectal adenocarcinomas and may play an important role in cancer progression and patient survival.
Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Se Min
SM
Jang
Hulin
H
Han
Young Jin
YJ
Jun
Si-Hyong
SH
Jang
Kyueng-Whan
KW
Min
Jongmin
J
Sim
Hye In
HI
Ahn
Kang Hong
KH
Lee
Ki-Seok
KS
Jang
Seung Sam
SS
Paik
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000401:mortality; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C498601:CADM4 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D019394:Ki-67 Antigen