Zagouri et al. BMC Cancer 2010, 10:409 http://www.biomedcentral.com/1471-2407/10/409 R E S E A R C H A R T I C L E Open Access Decreased Hsp90 expression in infiltrative lobular carcinoma: an immunohistochemical study Flora Zagouri1,2, Theodoros Sergentanis1, Afrodite Nonni1,3, Christos Papadimitriou1,2, Anastasia Pazaiti1, Nikolaos V Michalopoulos1, Panagiotis Safioleas1, Andreas Lazaris2, George Theodoropoulos1, Effstratios Patsouris2, George Zografos1* Abstract Background: Elevated Hsp90 expression has been documented in breast ductal carcinomas, whereas decreased Hsp90 expression has been reported in precursor lobular lesions. This study aims to assess Hsp90 expression in infiltrative lobular carcinomas of the breast. Methods: Tissue specimens were taken from 32 patients with infiltrative lobular carcinoma. Immunohistochemical assessment of Hsp90 was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. Concerning Hsp90 assessment: i) the percentage of positive cells and ii) the intensity were separately analyzed. Subsequently, the Allred score was adopted and calculated. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3). Statistical analysis followed. Results: All infiltrative lobular carcinoma foci mainly presented with a positive cytoplasmic immunoreaction for Hsp90. Compared to the adjacent normal ducts and lobules, infiltrative lobular carcinoma exhibited a statistically significant decrease in Hsp90 expression, both in terms of Hsp90 positive cells (%) and Allred score (74.2 ± 11.2 vs. 59.1 ± 14.2 p = 0.0001; 7.00 ± 0.95 vs. 6.22 ± 1.01, p = 0.007, Wilcoxon matched-pairs signed-ranks test). Concerning the intensity of Hsp90 immunostaining only a marginal decrease was noted (2.16 ± 0.68 vs. 1.84 ± 0.63, p = 0.087, Wilcoxon matched-pairs signed-ranks test). Conclusion: ILC lesions seem to exhibit decreased Hsp90 expression, a finding contrary to what might have been expected, given that high Hsp90 expression is a trait of invasive ductal carcinomas. Background Hsp90 is an abundant protein in mammalian cells [1]. It forms several discrete complexes, each containing dis- tinct groups of cochaperones that assist protein folding and refolding during stress, protein transport and degra- dation [2]. Hsp90 interacts with a variety of proteins that play key roles in breast neoplasia; including estrogen receptors (ER), tumor suppressor p53 protein, angiogen- esis transcription factor HIF-1alpha, antiapoptotic kinase Akt, Raf-1 MAP kinase and a variety of receptor tyrosine kinases, such as erbB2 (reviewed in [3]). Elevated Hsp90 expression has been documented in breast ductal carcinomas [4-6] as contributing to the * Correspondence: gzografo@med.uoa.gr 1Breast Unit, 1stDepartment of Propaedeutic Surgery, Hippokratio Hospital, School of Medicine, University of Athens, Athens, Greece Full list of author information is available at the end of the article proliferative activity of breast cancer cells. Hsp90 over- expression has been proposed as a mechanism through which breast cancer cells become resistant to various stress stimuli [6]. In this context, higher Hsp90 expres- sion may represent a marker of poor prognosis [7]. Given the above, it would appear that pharmacological inhibition of Hsps can provide therapeutic opportunities in the field of cancer treatment [8-12]; 17- allylamino, 17-demethoxygeldanamycin (17-AAG), the first Hsp90 inhibitor to undergo clinical development, has yielded promising results [3,13]. As the above demonstrates, a wide variety of studies on Hsp90 expression in breast cancer have emerged; nevertheless, there is a marked scarcity of data on Hsp90 expression in lobular neo- plasia/infiltrative lobular carcinomas in particular. Contrary to what might have been expected, our pre- vious work in lobular neoplasia (LN) has demonstrated © 2010 Zagouri et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.