Möllerström et al. BMC Cancer 2010, 10:296 http://www.biomedcentral.com/1471-2407/10/296 R E S E A R C H A R T I C L E Open Access RUespea-rcrheargticulelation of cell cycle arrest protein BTG2 correlates with increased overall survival in breast cancer, as detected by immunohistochemistry using tissue microarray Elin Möllerström*1, Anikó Kovács2, Kristina Lövgren3, Szilard Nemes4, Ulla Delle1, Anna Danielsson1, Toshima Parris1, Donal J Brennan5, Karin Jirström6, Per Karlsson7 and Khalil Helou1 Abstract Background: Previous studies have shown that the ADIPOR1, ADORA1, BTG2 and CD46 genes differ significantly between long-term survivors of breast cancer and deceased patients, both in levels of gene expression and DNA copy numbers. The aim of this study was to characterize the expression of the corresponding proteins in breast carcinoma and to determine their correlation with clinical outcome. Methods: Protein expression was evaluated using immunohistochemistry in an independent breast cancer cohort of 144 samples represented on tissue microarrays. Fisher's exact test was used to analyze the differences in protein expression between dead and alive patients. We used Cox-regression multivariate analysis to assess whether the new markers predict the survival status of the patients better than the currently used markers. Results: BTG2 expression was demonstrated in a significantly lower proportion of samples from dead patients compared to alive patients, both in overall expression (P = 0.026) and cell membrane specific expression (P = 0.013), whereas neither ADIPOR1, ADORA1 nor CD46 showed differential expression in the two survival groups. Furthermore, a multivariate analysis showed that a model containing BTG2 expression in combination with HER2 and Ki67 expression along with patient age performed better than a model containing the currently used prognostic markers (tumour size, nodal status, HER2 expression, hormone receptor status, histological grade, and patient age). Interestingly, BTG2 has previously been described as a tumour suppressor gene involved in cell cycle arrest and p53 signalling. Conclusions: We conclude that high-level BTG2 protein expression correlates with prolonged survival in patients with breast carcinoma. Background Breast cancer is the most common malignancy among women, and accounted for approximately 1.15 million new cases and 411,000 deaths worldwide in 2002 [1]. During the last decade, the survival rate for breast cancer patients has increased dramatically due to earlier detec- tion and new treatment protocols [2]. Presently, various clinical and pathological markers including axillary lymph node status, hormone receptor status, histological * Correspondence: elin.mollerstrom@neuro.gu.se 1 Department of Oncology, Institute of Clinical Sciences, Blå stråket 2, University of Gothenburg, SE-413 45 Göteborg, Sweden Full list of author information is available at the end of the article grade, tumour size, patient age, HER2 expression and vascular invasion are used to predict breast cancer prog- nosis and provide accurate treatment [3]. However, these markers are insufficient and approximately 20 to 30% of breast cancer patients will die from the disease within five years of diagnosis [4]. It is, therefore, of great importance to identify novel molecular markers to further refine prognosis and response to treatment. Gene expression analysis has been used to develop gene expression signa- tures that predict clinical outcome in breast cancer patients [5-9]. Previously, we analysed breast tumours from lymph node-negative patients using gene expression microarray and array-CGH to identify genes with altered © 2010 Möllerström et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Com- mons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduc- tion in any medium, provided the original work is properly cited.