Decreased Hsp90 expression in infiltrative lobular carcinoma: an immunohistochemical study

Abstract

BackgroundElevated 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.MethodsTissue 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.ResultsAll 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).ConclusionILC 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.

Heat Shock Protein 90 (Hsp90) Expression and Breast Cancer

“…Contrary to the pathological findings published by our team [ 48 , 49 , 50 ], as well as by other research groups [ 45 , 46 , 47 , 51 ], according to which Hsp90 exhibits significant variability along both series, such a finding was not replicated at the level of Hsp90 serum concentrations [ 56 ].…”

“…Elevated Hsp90 expression has been documented in breast ductal carcinomas [ 44 , 45 , 46 , 47 , 48 ], whilst a significantly decreased Hsp90 expression has been shown in infiltrative lobular carcinomas and lobular neoplasia [ 49 , 50 ].…”

The Prognostic Significance of Hsp70/Hsp90 Expression in Breast Cancer: A Systematic Review and Meta-analysis

“…data indicated a reduction also evident between IDC and DCIS, as well as DCIS and normal breast tissue. Especially concerning lobular lesions Zagouri et al showed a significantly lower Hsp90 expression in lobular neoplasia and invasive lobular carcinomas, compared to the noncancerous breast tissue (32,33).…”

Ratio of proliferation markers and HSP90 gene expression as a predictor of pathological complete response in breast cancer neoadjuvant chemotherapy

“…The association of HSP90 gene expression with different pathological and clinical features of breast cancer has not yet been studied extensively in the novel setting of molecular subtypes of this disease. However, additionally to the suggestions that the role may be particularly associated with HER2-positive disease, there were also observations that HSP90 exhibits low expression in the lobular histotype [35].…”