Hsp90 in the continuum of breast ductal carcinogenesis: Evaluation in precursors, preinvasive and ductal carcinoma lesions

BMC Cancer

Research Article

Andreas Lazaris¹  Effstratios Patsouris¹  Afrodite Nonni¹  George C Zografos²  Philip Domeyer²  George Theodoropoulos²  Anastazia Pazaiti²  Eleni Zogafos²  Theodoros N Sergentanis²  Nikolaos V Michalopoulos²  Flora Zagouri³  Christos A Papadimitriou⁴ 

[1] 1st Department of Pathology, School of Medicine, University of Athens, Greece;Breast Unit, 1st Department of Propaedeutic Surgery, Hippokratio Hospital, School of Medicine, University of Athens, Greece;Breast Unit, 1st Department of Propaedeutic Surgery, Hippokratio Hospital, School of Medicine, University of Athens, Greece;Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece;Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece;

关键词: Invasive Ductal Carcinoma;    Hsp90 Expression;    Atypical Ductal Hyperplasia;    Lobular Neoplasia;    Allred Score;   

DOI  :  10.1186/1471-2407-10-353

 received in 2009-12-26, accepted in 2010-07-05,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundHsp90 (heat shock protein90) is a chaperone protein essential for preserving and regulating the function of various cellular proteins. Elevated Hsp90 expression seems to be a trait of breast cancer and may be an integral part of the coping mechanisms that cancer cells exhibit vis-à-vis stress. This manuscript tries to examine the immunohistochemical expression of Hsp90 all along the continuum of breast ductal lesions encompassing ductal hyperplasia without atypia (DHWithoutA), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC).MethodsTissue specimens were taken from 30 patients with DHWithoutA, 31 patients with ADH, 51 with DCIS and 51 with IDC. 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 the percentage of positive cells and the intensity were separately analyzed. Subsequently, the Allred score was calculated. Post hoc analysis on the correlations between Hsp90 Allred score and possible predictors (grade, nodal status, tumor size, ER Allred score, PR Allred score, c-erbB-2 status and triple negative status) was conducted in IDC.ResultsHsp90 exhibited mainly cytoplasmic immunoreactivity. Hsp90 Allred score exhibited an increasing trend along the continuum of breast ductal lesions (Spearman's rho = 0.169, p = 0.031). Compared to the adjacent normal ducts and lobules, no statistically significant differences were noted in DHwithoutA, ADH and DCIS. Hsp90 expression (intensity, positive cells, Allred score) was higher in IDC, compared to the adjacent normal tissue. Higher Hsp90 expression was observed in grade 2/3 IDCs (borderline association) and tumors of larger size. At the univariable analysis, higher Hsp90 expression was associated with higher ER Allred score, PR Allred score and c-erbB-2 positivity in IDC. Triple-negative IDCs exhibited significantly lower Hsp90 expression. The multivariable logistic regression model revealed that between the three markers, solely ER Allred score and c-erbB-2 positivity were independently associated with higher Hsp90 expression in IDC.ConclusionThe above point to significant variability in Hsp90 expression with significant implications upon the effectiveness and limitations of anti-Hsp90 drugs.

【 授权许可】

Unknown   
© Zagouri et al; licensee BioMed Central Ltd. 2010. This article is published under license to 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.