Determination of predictive markers related to micro-metastasis in breast cancer patients
Abstract of thesis entitled
?etermination of Predictive Markers Related to Micro-Metastasis in Breast Cancer Patients?Submitted by
for the degree of Master of Philosophy
at The University of Hong Kong
in November 2004
Breast cancer is the most common malignancy in women, both in Hong Kong and other developed countries, and is also a leading cause of female mortality, resulting in over 300,000 deaths annually. Metastasis is the single largest contributing factor to breast cancer mortality. Early detection of metastasis will improve breast cancer outcomes in many cases, and it is therefore important to improve detection techniques. Early detection of metastasis is now possible via new methods that detect so-called micro- metastasis. However, merely detecting micro- metastasis provides no information on the biological characteristics of disseminated cancer cells. In order to dissect the metastasis cascade in breast cancer patients, a more careful analysis is necessary to extract more information from these cell clusters. This study therefore attempts to identify the association between micro- metastasis in local and distant
homing sites, and most importantly, to determine a more exact relationship between primary tumors and micro- metastasis in different homing sites, emphasizing potential clinical applications.
A systemic study was conducted on clinical samples, including primary tumors, sentinel lymph nodes, blood and bone marrow. A series of genes (Her2/neu, COX-2, VEGF, PDGFB, PTEN) known to play important roles in breast cancer progression and metastasis was examined. Using magnetic enhancement assays, we showed that peripheral blood might be an ideal source for the detection of circulating tumor cells, partly because it offered a convenient sampling procedure and also because of its important predictive value in respect of bone marrow micro- metastasis. Our data also suggested that lymphogenic and hematogenic spread might be two independent metastatic pathways in breast cancer.
More importantly, the current study provides clinical evidence that the overexpression of Her2/neu, COX-2 and VEGF and loss of expression of PTEN was associated with the presence of micro- metastasis in SLN, while PDGFB was associated with micro- metastasis in blood and BM, suggesting that they may be of value for the diagnosis of micro- metastasis situated in different homing sites. The study of gene expression suggested that COX-2 detected by quantitative RT-PCR is associated with SLN detected by H& E, and that protein expression detected by IHC can predict micrometastatic spread. Further work may provide the information to enable early tumor cell dissemination to be predicted with greater accuracy, and enable us to stratify breast cancer patients at high risk of metastasis to be for different treatment modalities and identify those at lower risk who may not need further systemic therapy.
School:The University of Hong Kong
School Location:China - Hong Kong SAR
Source Type:Master's Thesis
Keywords:metastasis diagnosis tumor markers breast cancer genetic aspects
Date of Publication:01/01/2005