Article

Delay to formalin fixation effect on breast biomarkers.

Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Modern Pathology (Impact Factor: 6.36). 10/2009; 22(11):1457-67. DOI: 10.1038/modpathol.2009.117
Source: PubMed

ABSTRACT Delay to formalin fixation may invalidate hormone receptors and HER2 analyses. Invalid results of tumor markers could significantly alter the type of adjuvant therapy a patient receives and potentially impact outcome. The purpose of this study was to determine the effects of progressive delay to formalin fixation on breast cancer biomarkers. Ten palpable invasive breast cancers were resected and underwent immediate gross evaluation. For each case, the procured tumor was divided into eight parts and consecutively fixed after 0, 10, 30 min, 1, 2, 4, and 8 h; one section was kept in saline and stored overnight at 4 degrees C. Two tissue microarray blocks were constructed. Estrogen and progesterone receptors and HER2 immunohistochemistry and fluorescence in situ hybridization were carried out. Statistical analyses including non-parametric sign test, exact McNemar's test and Page's L test were used. All 10 cases were invasive ductal carcinomas. Q score > or =6 was identified in five cases for estrogen receptor and four for progesterone receptor. Mean Q score started to decline at the 2 h mark for estrogen receptor and 1 h mark for progesterone receptor. Lowest score was at 8 h mark for estrogen receptor and overnight for progesterone receptor. HER2 fluorescence in situ hybridization started to be compromised for interpretation at the 1 h mark and became statistically significant at the 2 h mark (P<0.03). To avoid delay to formalin fixation as a factor negatively affecting on breast biomarkers, we recommend not to delay formalin fixation for more than 1 h and not to store specimens overnight.

Full-text

Available from: Sheila N J Sait, Jun 04, 2014
0 Followers
 · 
98 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although the analysis of hormone receptors and HER-2/neu has usually been performed on primary tumors only, a growing body of evidence suggests that substantial discordance exists between primary and metastatic disease for estrogen receptors (30-40%) and HER-2/neu (10-30%). This discordance may reflect alterations in pathologic assessment techniques, changes between primary and metastatic breast cancer, differences within a heterogenous tumor, or the effect of treatment. The etiology of discordance is poorly understood and frequently may reflect tumor heterogeneity along with lack of standardized preanalytic and analytic variables. Standardization of diagnostic variables can improve diagnostic reproducibility. Because of the emergence of targeted hormonal and HER-2/neu therapies, tumor biomarkers assume a pivotal role in treatment decisions. The loss of sensitivity to hormones or HER-2/neu may suggest tumor resistance; whereas, the acquisition of hormone receptors and HER-2/neu provides potential new treatment targets which can improve overall patient outcomes.
    Cancer biomarkers: section A of Disease markers 01/2012; 12(6):219-30. DOI:10.3233/CBM-130317 · 1.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and aim: Core needle biopsies (CNB) are now routinely performed for the clinical approach of patients with suspected breast cancer (BC). We explored the degree of concordance between CNB and surgical excised specimens (SES) regarding histological type, grade and immunohistochemistry (IHC) status. Patients and methods: We included 162 patients who underwent CNB before surgical resection. Immunohistochemistry for ER, PR, HER2 and Ki-67 was performed. Kappa test was used to obtain the concordance rate between CNB and SES regarding their histological type, grade and IHC profile. Sensitivity, specificity, PPV and NPV were calculated for CNB, considering SES as gold standard. Results: The concordance rate for histological type was 82.76% (κ = 0.49; p < 0.00). The general agreement for ER was 87.3% (κ = 0.71; p < 0.00). Nine cases were positive to PR in CNB and negative in SES, while the opposite occurred in 15 cases. We detected the highest concordance rate for HER2 expression (91.6%, κ = 0.74; p < 0.00). The calculated NPV was 98.5% for HER2 expression. Conclusions: We demonstrate that a CNB is a reliable tool for the diagnostic work-up of BC patients. A HER2 negative result should be reassuring for the clinician; however every hormone receptor negative in CNB should be regularly re-tested.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Digital pathology and the adoption of image analysis have grown rapidly in the last few years. This is largely due to the implementation of whole slide scanning, advances in software and computer processing capacity and the increasing importance of tissue-based research for biomarker discovery and stratified medicine. This review sets out the key application areas for digital pathology and image analysis, with a particular focus on research and biomarker discovery. A variety of image analysis applications are reviewed including nuclear morphometry and tissue architecture analysis, but with emphasis on immunohistochemistry and fluorescence analysis of tissue biomarkers. Digital pathology and image analysis have important roles across the drug/companion diagnostic development pipeline including biobanking, molecular pathology, tissue microarray analysis, molecular profiling of tissue and these important developments are reviewed. Underpinning all of these important developments is the need for high quality tissue samples and the impact of pre-analytical variables on tissue research is discussed. This requirement is combined with practical advice on setting up and running a digital pathology laboratory. Finally, we discuss the need to integrate digital image analysis data with epidemiological, clinical and genomic data in order to fully understand the relationship between genotype and phenotype and to drive discovery and the delivery of personalized medicine.
    Methods 11/2014; 70(1). DOI:10.1016/j.ymeth.2014.06.015 · 3.22 Impact Factor