ERBB family in breast cancer: Detection methods, clinical and prognostic significance, under-recognized mechanisms in their function

Historically the definition of an ERBB2 positive status was based on arbitrary assumptions. Even with the current level of clinical validation, it is reasonable to assume that it will be further refined into a more precise definition in the future. There is a need to develop alternative approaches to ERBB receptor family, in the first place to ERBB2 testing to overcome the limitation of the current assays and meet the demand of clinical practice. Ideally new ERBB assay should be accurate, robust, reliable, simple to use, cost-effective, easy to standardise and capable of high sample throughput. Our research project has carried out different methods and tests, trying to contribute to this persistent requirement. We approached this problem by comparison of molecular and immunolo-histochemical techniques to evaluate ERBB2 status at DNA, at mRNA and at protein level. We found high degree of concordance between ICH and FISH and mRNA techniques. Further we studied the relationship and eventual correlation between ERBB2 status and different clinical, pathological and biological factors. We studied and demonstrated the ERBB2 status on various populations as node negative, post-menopausal or metastatic breast cancer. Our team developed and validated a new method to measure ERBB2 gene expression at mRNA level, a method, which seems to fulfil and able to response the above mentioned criteria. At last, we widened this technique to investigate the mRNA expression for each member of the ERBB family and to examine their prognostic values in breast cancer. Our data illustrated different levels of expression of the ERBB genes in mammary carcinoma. These facts suggest to widen the use of classical detection test (ERBB2) to all members of the ERBB family, thus optimising the therapeutical approach of breast cancer patients.