Heat shock protein90 in lobular neoplasia of the breast

<p>Abstract</p> <p>Background</p> <p>Heat shock protein 90 (Hsp90) overexpression has been implicated in breast carcinogenesis, with putative prognostic and therapeutic implications. The purpose of this study is to evaluate the immunohistochemical expression of Hsp90 and to examine whether Hsp90 expression is associated with estrogen receptor alpha (ER-alpha) and beta (ER-beta) immunostaining in lobular neoplasia (LN) of the breast.</p> <p>Methods</p> <p>Tissue specimens were taken from 44 patients with LN. Immunohistochemical assessment of Hsp90, ER-alpha and ER-beta was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. As far as Hsp90 evaluation is concerned: i) the percentage of positive cells, and ii) the intensity was separately analyzed. Additionally, the Allred score was adopted and calculated. Accordingly, Allred score was separately evaluated for ER-alpha and ER-beta. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3). Statistical analysis followed.</p> <p>Results</p> <p>Hsp90 immunoreactivity was mainly cytoplasmic in both the epithelial cells of normal breast (ducts and lobules) and LN. Some epithelial cells of LN also showed nuclear staining, but all the LN foci mainly disclosed a positive cytoplasmic immunoreaction for Hsp90. In addition, rare intralobular inflammatory cells showed a slight immunoreaction. The percentage of Hsp90 positive cells in the LN areas was equal to 67.1 ± 12.2%, whereas the respective percentage in the normal adjacent breast tissue was 69.1 ± 11.6%; the difference was not statistically significant. The intensity score of Hsp90 staining was 1.82 ± 0.72 in LN foci, while in the normal adjacent tissue the intensity score was 2.14 ± 0.64. This difference was statistically significant (p = 0.029, Wilcoxon matched-pairs signed-ranks test). The Hsp90 Allred score was 6.46 ± 1.14 in the LN foci, significantly lower than in the normal adjacent tissue (6.91 ± 0.92, p = 0.049, Wilcoxon matched-pairs signed-ranks test). Within the LN foci, the Hsp90 Allred score was neither associated with ER-alpha, nor with ER-beta percentage.</p> <p>Conclusion</p> <p>Hsp90 was lower in LN foci both at the level of intensity and Allred score, a finding contrary to what might have been expected, given that high Hsp90 expression is detected in invasive breast carcinomas. Hsp90 deregulation does not seem to be a major event in LN pathogenesis.</p

Decreased Hsp90 expression in infiltrative lobular carcinoma: an immunohistochemical study

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 a

Is zero underestimation feasible? Extended Vacuum-assisted breast biopsy in solid lesions – a blind study

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Quantitative measurement of olivine composition in three dimensions using helical-scan X-ray micro-tomography

Olivine is a key constituent in the silicate Earth; its composition and texture informs petrogenetic understanding of numerous rock types. Here we develop a quantitative and reproducible method to measure olivine composition in three dimensions without destructive analysis, meaning full textural context is maintained. The olivine solid solution between forsterite and fayalite was measured using a combination of three-dimensional (3D) X-ray imaging techniques, 2D backscattered electron imaging, and spot-analyses using wavelength-dispersive electron probe microanalysis. The linear attenuation coefficient of natural crystals across a range of forsterite content from ∼73–91 mol% were confirmed to scale linearly with composition using 53, 60, and 70 kV monochromatic beams at I12-JEEP beamline, Diamond Light Source utilizing the helical fly-scan acquisition. A polychromatic X-ray source was used to scan the same crystals, which yielded image contrast equivalent to measuring the mol% of forsterite with an accuracy of 3 mm domains within a large crystal of San Carlos forsterite that varies by ∼2 Fo mol%. This offers a solution to an outstanding question of inter-laboratory standardization, and also demonstrates the utility of 3D, non-destructive, chemical measurement. To our knowledge, this study is the first to describe the application of XMT to quantitative chemical measurement across a mineral solid solution. Our approach may be expanded to calculate the chemistry of other mineral systems in 3D, depending upon the number, chemistry, and density of end-members

p63 expression in benign and malignant breast lesions

The p63 gene encodes six protein isoforms. The transactivating isoforms have similar actions with p53, while the N-isoforms inhibit transcription activation by p53 and transactivating isoforms. p63 is expressed in stratified epithelia and in basal cells of the prostate and salivary glands. In mammary epithelium p63 has been shown to be expressed only in the myoepithelial layer. In the present study we investigated the immunohistochemical expression of p63, in benign and malignant breast lesions, and compared it with known myoepithelial cell markers. Our material consisted of 140 benign and 126 malignant breast lesions. We used the antibodies anti-p63, anti-a-smooth muscle actin, anti-S-100 protein and anti-cytokeratin 14. In all benign lesions, p63 immunoreactivity was noted in the myoepithelial cell layer surrounding the luminal epithelial cells. A less continuous peripheral rim of myoepithelial cells was also highlighted with p63- staining in all situ carcinomas. All invasive breast carcinomas were devoided of peripheral p63 staining. Interestingly, strong nuclear p63 immunoreactivity was noted in a small fraction (5-15%) of epithelial cells in all cases of papillomatosis, in 62.5% of in situ ductal papillary-type carcinomas and in 33.3% of invasive papillary carcinomas. Comparable staining was observed with S-100. The stromal cells were unreactive to p63. Our findings suggest that p63 is a sensitive and specific myoepithelial marker, and may be included in immunohistochemical panels aiming to identify myoepithelial cells in problematic breast lesions. Regarding papillary neoplasms, it is possible that tumor cells acquire and exhibit at least in part a myoepithelial differentiation program

p63 expression in benign and malignant breast lesions

The p63 gene encodes six protein isoforms. The transactivating isoforms have similar actions with p53, while the N-isoforms inhibit transcription activation by p53 and transactivating isoforms. p63 is expressed in stratified epithelia and in basal cells of the prostate and salivary glands. In mammary epithelium p63 has been shown to be expressed only in the myoepithelial layer. In the present study we investigated the immunohistochemical expression of p63, in benign and malignant breast lesions, and compared it with known myoepithelial cell markers. Our material consisted of 140 benign and 126 malignant breast lesions. We used the antibodies anti-p63, anti-alpha-smooth muscle actin, anti-S-100 protein and anti-cytokeratin 14. In all benign lesions, p63 immunoreactivity was noted in the myoepithelial cell layer surrounding the luminal epithelial cells. A less continuous peripheral rim of myoepithelial cells was also highlighted with p63-staining in all situ carcinomas. All invasive breast carcinomas were devoided of peripheral p63 staining. Interestingly, strong nuclear p63 immunoreactivity was noted in a small fraction (5-15%) of epithelial cells in all cases of papillomatosis, in 62.5% of in situ ductal papillary-type carcinomas and in 33.3% of invasive papillary carcinomas. Comparable staining was observed with S-100. The stromal cells were unreactive to p63. Our findings suggest that p63 is a sensitive and specific myoepithelial marker, and may be included in immunohistochemical panels aiming to identify myoepithelial cells in problematic breast lesions. Regarding papillary neoplasms, it is possible that tumor cells acquire and exhibit at least in part a myoepithelial differentiation program.Histol Histopatho