The Effect of Cold Ischemia Time and/or Formalin Fixation on Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor-2 Results in Breast Carcinoma
Aims. To compare the results of estrogen and progesterone receptors (ER, PR), and human epidermal growth factor receptor-2 (HER2) expression status on biopsy and excision specimens and to evaluate the effect of cold ischemia time and/or formalin fixation on these biomarkers. Methods. Breast carcinomas that were diagnosed between 2007 and 2009 by core needle biopsy, and subsequently excised in our institution, were included in the study. Data regarding the tumor morphology, grade, and ER, PR, and HER2 status were retrospectively collected from the pathology reports. Results. Five out of 149 (3.4%) cases with ER-positive receptor status in the biopsy specimen became ER-negative in the subsequent excision specimen. Nine out of 126 (7.1%) cases with PR-positive receptor status in the biopsy specimen became PR-negative in the excision specimen. Receptor status change was predominantly seen in tumors with low ER and PR receptor expression. HER2 results were consistent between biopsy and excision specimens in all cases tested. Conclusions. Cold ischemia time and/or formalin fixation affect mainly ER and PR testing with low Allred scores and support the implementation of the ASCO/CAP guidelines. HER2 results, however, were not affected in our limited number of patients. 1. Introduction Breast cancer is one of the best examples where antibody-defined tumor markers are used as both prognostic and predictive factors. Prognostic factors are independently associated with the clinical outcome, whereas predictive factors are independently associated with response or lack of response to a particular treatment. Estrogen receptor (ER) expression is a positive prognostic marker of outcome and a strong predictive marker of response to hormone-based therapies such as tamoxifen [1, 2]. Similarly, progesterone receptor (PR) expression is correlated with better prognosis and higher response to hormone-based treatments and increases the predictive power of ER [3–5]. Yet another important marker in the evaluation of breast cancer is the human epidermal growth factor receptor-2 (HER2; c-erbB-2), which is a member of the epidermal growth factor receptor family. HER2 overexpression and/or gene amplification have been shown to be a poor prognostic factor in breast cancer [6, 7]. HER2 status is also predictive for sensitivity to anthracycline-based chemotherapies and relative resistance to cytoxan-based and tamoxifen-based adjuvant therapies [8]. Moreover, it is essential for the therapeutic decisions regarding the use of agents targeting the HER2 gene product such as the humanized,
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