Separating favorable from unfavorable prognostic markers in breast cancer:The role of E-cadherin

Citation
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
Citations number
59
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
0008-5472 → ACNP
Volume
60
Issue
2
Year of publication
2000
Pages
298 - 304
Database
ISI
SICI code
0008-5472(20000115)60:2<298:SFFUPM>2.0.ZU;2-M
Abstract
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.