Reduced E-cadherin expression is associated with invasiveness and unfavorable prognosis in breast cancer.
E-cadherin (E-cad) is a calcium-dependent, epithelial cell adhesion molecule whose reduced or lost expression has been associated with tumor dedifferentiation and increased metastatic potential in human carcinomas. The authors studied immunohistochemically E-cad expression in frozen sections of 362 breast carcinomas using a monoclonal antibody (HECD-1). The immunohistochemical detection of reduced E-cad expression was confirmed by mRNA in situ hybridization with two different oligonucleotide probes. THe proportion of tumors with reduced or lost E-cad expression increased significantly from pure intraductal carcinomas (20%, 4 of 20) through invasive ductal (IDCs; 52%, 124 of 239) to recurrent carcinomas (64%, 18 of 28; chi square test for trend, P = .004). Invasive lobular carcinomas (ILCs) and IDCs differed from each other in their E-cad expression. None of the ILCs (n=55) retained normal E-cad expression in contrast to 48% (115 of 239) of the IDCs. In 259 primary IDCs, reduced E-cad expression was associated with high histologic grade (chi square test for trend, P < .001), negative estrogen receptor status (ER; Fisher's exact test; P = .042), and marginally with axillary node involvement (Fisher's exact test, P = .063). In a subset of 109 primary IDC patients whose clinical follow-up was available (median follow-up 51 months), reduced E-cad expression was associated with shortened disease-free survival (DFS; Mantel-Cox test, P = .027). In Cox's multivariate regression analysis, progesterone receptor status (P = .018) and E-cad expression (P = .072) were selected as independent predictors of DFS. Our findings provide clinical evidence that loss of normal E-cad expression is an indicator of increased invasiveness and dedifferentiation in breast carcinoma. E-cad is a potentially important prognostic factor in primary IDCs.
Siitonen
S M
SM
Department of Clinical Chemistry, Tampere University Hospital, Finland.
Kononen
J T
JT
Helin
H J
HJ
Rantala
I S
IS
Holli
K A
KA
Isola
J J
JJ
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012334:RNA, Neoplasm / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
D000911:Antibodies, Monoclonal; D015820:Cadherins; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone