R. Heimann et al., Separating favorable from unfavorable prognostic markers in breast cancer:The role of E-cadherin, CANCER RES, 60(2), 2000, pp. 298-304
Distant metastases are the major cause of morbidity and mortality in women
with breast cancer. The ability to predict the metastatic proclivity is ess
ential in choosing the optimal treatment, Tumor size and grade, which are f
requently used markers in node-negative breast cancer patients, are inadequ
ate markers for prognosis and individualized treatment design. The steps in
metastatic progression include angiogenesis, invasion, and changes in adhe
sion characteristics. We del eloped a strategy for choosing biomarkers repr
esenting these steps in malignant progression to identify patients with occ
ult metastases who will need chemotherapy and spare those women whose tumor
s have not developed the capacity to spread. To evaluate the added signific
ance of E-cadherin to that of nm23-H1 and angiogenesis in determining metas
tatic proclivity, we used archival material from 168 node-negative breast c
ancer patients who were treated with mastectomy without any adjuvant chemot
herapy or hormone therapy, Immunohistochemistry was used to detect E-cadher
in and nm23-H1 expression, whereas angiogenesis was determined by microvess
el count (MVC) after immunohistochemical staining, The median follow-up is
14 years. We found that E-cadherin is better in identifying the poor progno
sis patients. The 14-year disease-free survival (DFS) is 84%, 80%, and 56%
in patients with high, intermediate, and lon E-cadherin, The worst prognosi
s group using nm23-H1 and MVC as biomarkers has a 14-year DFS of 62%. In th
is group, if E-cadherin is low, the 14-year DFS is further decreased to 44%
. Nm23-H1 and MVC are better in identifying the good prognosis patients. Th
e long-term DFS is >90% if MVC is low or if nm23-H1 is high. Multivariate a
nalysis shows that E-cadherin, nm23-H1, and MVC are more significant progno
stic biomarkers than tumor size or grade. Loss of E-cadherin appears to be
a latter step in the metastatic progression compared to angiogenesis and th
e loss of nm23-H1 expression.