) The high cure rate of germ cell tumors (GCTs) challenges us to identify patients destined to fail standard therapies. We hypothesize that PCR for beta-HCG and AFP RNA can detect circulating GCT cells and provide prognostic information based on the metastatic potential of GCTs.
The specific aims of this proposal are:
Specific Aim 1 : Evaluate PCR for beta-HCG as a diagnostic tool in predicting disease relapse after autologous marrow and stem cell transplantation (AuBMT) for GCTs. In a pilot study, beta-HCG PCR detected circulating tumor cells in the apheresis products of approximately one-third of GCT patients undergoing AuBMT. We hypothesize that detection of circulating tumor cells will predict relapse after AuBMT.
We aim to test this hypothesis and also determine if beta-HCG PCR can be utilized to monitor tumor cell depletion methods, specifically CD34 selection.
Specific Aim 2 : Evaluate PCR for beta-HCG as a prognostic tool in patients undergoing initial chemotherapy and those treated with surgery alone. Our preliminary evidence indicates that mRNA for beta-HCG can be detected in the blood of certain GCT patients at diagnosis. We hypothesize that beta- HCG PCR at diagnosis can be used to predict relapse after standard GCT therapies. We proposed to study the same patients undergoing initial chemotherapy treatment being evaluated in Projects 1-3 and analyzed in the prognostic models being tested in Core B.
Specific Aim 3 : Define beta-HCG gene expression within the beta-HCG locus in GCTs and develop alternate diagnostic tools in detecting circulating GCT cells in tumors that do not express beta-HCG. The beta-HCG gene locus contains six gene copies. We propose to evaluate GCT samples for the expression of beta-HCG genes within the beta-HCG gene locus and determine whether detected difference can be exploited for diagnostic and predictive testing. Also, approximately one-third of GCT in advanced GCT patients do not express beta-HCG but may express other molecules. We will evaluate expression of alpha fetoprotein (AFP) as an alternative molecular marker in patients whose tumors do not express beta-HCG.
