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Positive association of up‐regulated Cripto‐1 and down‐regulated E‐cadherin with tumour progression and poor prognosis in gastric cancer
Author(s) -
Zhong XY,
Zhang LH,
Jia SQ,
Shi T,
Niu ZJ,
Du H,
Zhang GG,
Hu Y,
Lu AP,
Li JY,
Ji JF
Publication year - 2008
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2008.02971.x
Subject(s) - cadherin , cancer , metastasis , medicine , immunohistochemistry , epithelial–mesenchymal transition , oncology , stage (stratigraphy) , cancer research , pathology , biology , genetics , cell , paleontology
Aims: Cripto‐1 may be capable of up‐regulating signalling molecules associated with epithelial‐to‐mesenchymal transition (EMT), an important event characterized by loss of E‐cadherin during malignant tumour progression and metastasis. The aim was to investigate the expression of Cripto‐1 and E‐cadherin in relation to clinicopathological features and patient prognosis of gastric cancer. Methods and results: The expression of Cripto‐1 and E‐cadherin was studied by immunohistochemistry in 118 gastric cancer cases. Up‐regulated Cripto‐1 (CR+) was found in 54% (64/118) of cases, whereas down‐regulated E‐cadherin (E‐cad−) was found in 70% (83/118) of cases. Either CR+ or E‐cad− was associated with lymph node metastasis, liver metastasis and late TNM stage ( P < 0.05). Patients with either CR− or E‐cad+ showed higher 5‐year survival rates than those with CR+ or E‐cad− ( P = 0.0012 and P = 0.0017, respectively). When combined, evaluation of these two proteins, simultaneous CR+ and E‐cad− (CR+/E‐cad−) in cancer was strongly associated with the above three aggressive clinicopathological features ( P < 0.001) and indicated the worst patient survival ( P = 0.0001). Multivariate analysis revealed that CR+/E‐cad− was an independent prognostic factor in gastric cancer. Conclusions: Combined analysis of Cripto‐1 and E‐cadherin has significant value in evaluating the metastatic potential of gastric cancer and predicting patient prognosis.