| Summary: | This thesis examines some aspects of the molecular pathology of breast cancer. Disregulation of the c-erb B2 oncogene was related to several histopathological and biochemical features of breast cancer. Other genes, specifically THRA1 and urokinase plasminogen activator were investigated for disregulation and possible interaction with c-erb B2 in the biology of breast cancer. A differential PCR technique for the detection of c-erb B2 gene amplification, was tested and validated for use on paraffin embedded methacarn fixed breast cancer tissues. Tissues from 314 breast cancers and 43 control samples were assessed for c-erb B2 gene amplification by dPCR. In clinical material the results were not affected by the DNA contribution of normal tissue elements or by cancer DNA ploidy change. C-erb B2 gene amplification was detected in 55% of invasive cancers and in 66% of <I>in situ</I> cancers. C-erb B2 protein overexpression in breast cancer cells, as determined by specific immunohistochemistry, was only detected in 11% of invasive cancers and 43% of <I>in situ</I> cancers. Comparisons show that a substantial number of cancers with c-erb B2 amplification lack detectable protein overexpression. The nature of c-erb B2 gene disregulation in breast cancer appears to be complex and multiple combinations of biological events are suggested. A model for the involvement of c-erb B2 in breast cancer progression is proposed. Mechanisms of c-erb B2 gene amplification and interaction with other cellular proteins are discussed.
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