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

Serum proteome analysis for profiling protein markers associated with carcinogenesis and lymph node metastasis in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC), one of the most common cancers in population with Chinese or Asian progeny, poses a serious health problem for southern China. It is unfortunate that most NPC victims have had lymph node metastasis (LNM) when first diagnosed. We believe that the 2D based serum proteome analysis can be useful in discovering new biomarkers that may aid in the diagnosis and therapy of NPC patients. To filter the tumor specific antigen markers of NPC, sera from 42 healthy volunteers, 27 non-LNM NPC patients and 37 LNM NPC patients were selected for screening study using 2D combined with MS. Pretreatment strategy, including sonication, albumin and immunoglobulin G (IgG) depletion, was adopted for screening differentially expressed proteins of low abundance in serum. By 2D image analysis and MALDI-TOF-MS identification, twenty-three protein spots were differentially expressed. Three of them were further validated in the sera using enzyme-linked immunosorbent assay (ELISA). Our research demonstrates that HSP70, sICAM-1 and SAA, confirmed with ELISA at sera and immunohistochemistry, are potential NPC metastasis-specific serum biomarkers which may be of great underlying significance in clinical detection and management of NPC

Imaging in situ breast carcinoma (with or without an invasive component) with technetium-99m pentavalent dimercaptosuccinic acid and technetium-99m 2-methoxy isobutyl isonitrile scintimammography

INTRODUCTION: The aim of the study was to retrospectively define specific features of the technetium-99m pentavalent dimercaptosuccinic acid ((99m)Tc-(V)DMSA) and technetium-99m 2-methoxy isobutyl isonitrile ((99m)Tc-Sestamibi [(99m)Tc-MIBI]) distribution in ductal breast carcinoma in situ and lobular breast carcinoma in situ (DCIS/LCIS), in relation to mammographic, histological and immunohistochemical parameters. MATERIALS AND METHODS: One hundred and two patients with suspicious palpation or mammographic findings were submitted preoperatively to scintimammography (a total of 72 patients with (99m)Tc-(V)DMSA and a total of 75 patients with (99m)Tc-Sestamibi, 45 patients receiving both radiotracers). Images were acquired at 10 min and 60 min, and were evaluated for a pattern of diffuse radiotracer accumulation. The tumor-to-background ratios were correlated (T-pair test) with mammographic, histological and immunohistochemical characteristics. RESULTS: Histology confirmed malignancy in 46/102 patients: 20/46 patients had DCIS/LCIS, with or without coexistent invasive lesions, and 26/46 patients had isolated invasive carcinomas. Diffuse (99m)Tc-(V)DMSA accumulation was noticed in 18/19 cases and (99m)Tc-Sestamibi in 6/13 DCIS/LCIS cases. Epithelial hyperplasia demonstrated a similar accumulation pattern. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value for each tracer were calculated. Solely for (99m)Tc-(V)DMSA, the tumor-to-background ratio was significantly higher at 60 min than at 10 min and the diffuse uptake was significantly associated with suspicious microcalcifications, with the cell proliferation index ≥ 40% and with c-erbB-2 ≥ 10%. CONCLUSION: (99m)Tc-(V)DMSA showed high sensitivity and (99m)Tc-Sestamibi showed high specificity in detecting in situ breast carcinoma ((99m)Tc-(V)DMSA especially in cases with increased cell proliferation), and these radiotracers could provide clinicians with preoperative information not always obtainable by mammography

Gene therapy for carcinoma of the breast: Pro-apoptotic gene therapy

The dysregulation of apoptosis contributes in a variety of ways to the malignant phenotype. It is increasingly recognized that the alteration of pro-apoptotic and anti-apoptotic molecules determines not only escape from mechanisms that control cell cycle and DNA damage, but also endows the cancer cells with the capacity to survive in the presence of a metabolically adverse milieu, to resist the attack of the immune system, to locally invade and survive despite a lack of tissue anchorage, and to evade the otherwise lethal insults induced by drugs and radiotherapy. A multitude of apoptosis mediators has been identified in the past decade, and the roles of several of them in breast cancer have been delineated by studying the clinical correlates of pathologically documented abnormalities. Using this information, attempts are being made to correct the fundamental anomalies at the genetic level. Fundamental to this end are the design of more efficient and selective gene transfer systems, and the employment of complex interventions that are tailored to breast cancer and that are aimed concomitantly towards different components of the redundant regulatory pathways. The combination of such genetic modifications is most likely to be effective when combined with conventional treatments, thus robustly activating several pro-apoptotic pathways

Assessment of voice quality after carotid endarterectomy

Objectives: vocal cord paralysis is considered a rare complication of carotid endarterectomy (CEA), but alteration in voice quality may be more common. The aim of this prospective study was to evaluate the effect of CEA on voice quality and to correlate any changes with the extent of the dissection. Design - Material - Methods: thirty-five patients who underwent CEA were divided in two groups, according to the level of surgical dissection performed. The high-level dissection group was comprised of those patients that required mobilisation of hypoglossal nerve and division of the posterior belly of digastric muscle. The low-level dissection group included the rest. All the patients’ voices were recorded and analysed digitally before CEA, one and three months after the operation. Voice data were measured for standard deviation of fundamental frequency, jitter, shimmer and normalised noise energy (NNE). All patients underwent a laryngeal examination pre- and post-operation. Results: none of the patients had any vocal cord dysfunction on laryngoscopy. Significant changes of voice quality (jitter, shimmer, NNE) were noticed in the high-level dissection group (p &lt; 0.05) one month after the operation: Two months later, the voice changes had subsided, but still significant disturbances remained (jitter, shimmer). Conclusions: voice-related disturbances are far more common following CEA than is generally believed and, although they seem to for the most part temporary, they deserve attention. Specifically, high-level surgical dissection seems to be a risk factor of postoperative vocal impairment