Expression of E-cadherin, beta-catenin, cathepsin D, gelatinases and their inhibitors in invasive ductal breast carcinomas.
BACKGROUND
E-cadherin, beta-catenin, cathepsin D, matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 are all invasion-related proteins. The expression patterns of these proteins in invasive ductal breast carcinomas, and their associations with known clinicopathological parameters, tumor recurrence and expressions of estrogen receptor (ER), progesterone receptor (PR), PS2 and c-erbB2 were not well studied in Chinese patients.


METHODS
In a set of 94 invasive ductal breast carcinomas, protein expressions of these molecular markers were investigated by immunohistochemistry, and their associations with known clinicopathological parameters, tumor recurrence and expressions of ER, PR, PS2 and c-erbB2 were also examined. In addition, the interrelationship between the expressions of these proteins were studied.


RESULTS
Preserved membrane E-cadherin expression was associated with late tumor stage and tumor recurrence, whereas the reduced junctional beta-catenin associated with positive lymph node status and c-erbB2 overexpression. Positive staining of cathepsin D in tumor stromal cells displayed a significant association with late tumor stage. High expression of MMP-2 in cancer cells was associated with large tumor size and PR positive expression. TIMP-2 expression was positively associated with tumor recurrence. In addition, inter-relationship between the expressions of these biomarkers was also assessed. Cathepsin D staining in cancer cells was inversely correlated with its staining in stromal cells, and also inversely correlated with MMP-2 staining in tumor stromal cells. MMP-2 expression in stromal cells displayed an inverse correlation with TIMP-2 expression. MMP-9 expression displayed parallel associations with TIMP-1 and TIMP-2 expression.


CONCLUSIONS
Evaluation of E-cadherin, beta-catenin, cathepsin D, MMP-2 and TIMP-2 expression may be of some help in more accurately predicting the prognosis of invasive ductal breast carcinomas.
Zhang
Yun-Gang
YG
Department of Pathology, Peking University Health Science Center, Beijing, China.
DU
Juan
J
Tian
Xin-Xia
XX
Zhong
Yan-Feng
YF
Fang
Wei-Gang
WG
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D015820:Cadherins / Q000032:analysis*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000473:pathology; D002402:Cathepsin D / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D051176:beta Catenin / Q000032:analysis*
D015820:Cadherins; D019715:Tissue Inhibitor of Metalloproteinase-1; D051176:beta Catenin; D019716:Tissue Inhibitor of Metalloproteinase-2; D002402:Cathepsin D; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9