HER2 overexpression in various tumor types, focussing on its relationship to the development of invasive breast cancer

To date, poor standardization in HER2 status evaluation has precluded relia ble comparison of overexpression rates in different tumors. However, standa rdized methodologies have been introduced recently for these analyses, and have identified frequencies of 51%, 44%, 26% and 25% in Wilm's tumor, bladd er, pancreatic and breast carcinoma, respectively. Other tumors tested had frequencies below 20%. The frequency was greater than that predicted by gen e amplification data in some tumor types, which may indicate overexpression due to gene deregulation, rather than gene amplification. Analysis of a la rge retrospective series of breast carcinomas demonstrated an association b etween HER2 positivity and a number of other prognostic markers. Together, these variables identify a subset of tumors with poor prognosis and early r elapse post-surgery. HER2 expression is relatively stable, with 95% concord ance between the HER2 status of primary and metastatic lesions. However, co ntralateral tumors are unrestricted with regard to HER2 status. Preliminary data indicate that the HER2 status of a hormone receptor-positive tumor ma y fluctuate according to the menstrual cycle. It is anticipated that the em erging wealth of standardized data for HER2 status will help to elucidate t he role of HER2 in tumor progression.