Metastatic cancer cells from c-erbB-2 negative primary breast cancer maintain the original c-erbB-2/HIF1alpha phenotype.
The expression of c-erbB-2 and HIF1alpha proteins is linked with an aggressive tumor phenotype and poor survival in breast cancer. In the present study we investigated whether this ominous effect is a result of c-erbB-2/HIF1alpha expressing clone appearance within the primary tumor, by examining the c-erbB-2/HIF1alpha expression status in the primary tumor, node metastasis and cancer cells invading into the lymphovascular spaces. The metastasizing cancer cell clones, whether migrating to the lymph nodes or entering into the systemic circulation maintained the original c-erbB-2/HIF1alphaphenotype of the primary tumor. Migrating c-erbB-2/HIF1alpha negative tumors do so through activation of alternative biologic pathways and not through positive clone appearance. These results strongly support the concept that targeted therapies against c-erbB-2 or against HIF1alpha can be guided with precision by the primary tumor c-erbB-2/HIF1alpha status without demanding the detection of the metastatic tumor phenotype.
Giatromanolaki
Alexandra
A
Department of Pathology, Democritus University of Thrace Medical School, Alexandroupolis 68100, Greece. targ@her.forthnet.gr
Koukourakis
Michael I
MI
Simopoulos
Costantinos
C
Sivridis
Efthimios
E
D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis / Q000235:genetics*; D010641:Phenotype; D014407:Tumor Cells, Cultured
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit