Breast angiosarcomas that are not related to previous radiotherapy are very rare. Surgical resection is the primary treatment for these tumors, but there is no general agreement on the extent of surgery. The role of multimodality adjuvant treatment also remains controversial. The aim of this study was to summarize the available data from the largest published series of patients in terms of management and outcome. We also sought to identify prognostic factors influencing patient survival. We have included studies presenting detailed data on multimodality therapy and survival of patients with breast angiosarcoma. Ten studies presenting data on 280 patients were included in the review. Seventy-five percent of patients underwent a total mastectomy and 25% had breast-conserving treatment (BCT). In 42% of patients, an axillary node dissection was combined with mastectomy or BCT. Thirty-six percent of patients received chemotherapy and 35% were treated with radiotherapy in an adjuvant or neoadjuvant setting. Survival varied significantly according to tumor size and grade. Adjuvant multimodality therapy may improve the outcome in selected patients with breast angiosarcoma. Tumor size, grade, and margin status are the most important prognostic factors for survival.
BackgroundHER2 and TOP2A parameters (gene status, mRNA and protein expression) have individually been associated with the outcome of patients treated with anthracyclines. The aim of this study was to comprehensively evaluate the prognostic/predictive significance of the above parameters in early, high-risk breast cancer patients treated with epirubicin-based, dose-dense sequential adjuvant chemotherapy.MethodsIn a series of 352 breast carcinoma tissues from patients that had been post-operatively treated with epirubicin-CMF with or without paclitaxel, we assessed HER2 and TOP2A gene status (chromogenic in situ hybridization), mRNA expression (quantitative reverse transcription PCR), as well as HER2 and TopoIIa protein expression (immunohistochemistry).ResultsHER2 and TOP2A amplification did not share the same effects on their downstream molecules, with consistent patterns observed in HER2 mRNA and protein expression according to HER2 amplification (all parameters strongly inter-related, p values < 0.001), but inconsistent patterns in the case of TOP2A. TOP2A gene amplification (7% of all cases) was not related to TOP2A mRNA and TopoIIa protein expression, while TOP2A mRNA and TopoIIa protein were strongly related to each other (p < 0.001). Hence, TOP2A amplified tumors did not correspond to tumors with high TOP2A mRNA or TopoIIa protein expression, while the latter were characterized by high Ki67 scores (p = 0.003 and p < 0.001, respectively). Multivariate analysis adjusted for nodal involvement, hormone receptor status, Ki67 score and HER2/TOP2A parameters revealed HER2/TOP2A co-amplification (21.2% of HER2 amplified tumors) as an independent favorable prognostic factor for DFS (HR = 0.13, 95% CI: 0.02-0.96, p = 0.046); in contrast, increased HER2/TOP2A mRNA co-expression was identified as an independent adverse prognostic factor for both DFS (HR = 2.41, 95% CI: 1.31-4.42, p = 0.005) and OS (HR = 2.83, 95% CI: 1.42-5.63, p = 0.003), while high TOP2A mRNA expression was an independent adverse prognostic factor for OS (HR = 2.06, 95% CI: 1.23-3.46, p = 0.006). None of the parameters tested was associated with response to paclitaxel.ConclusionsThis study confirms the favorable prognostic value of HER2/TOP2A co-amplification and the adverse prognostic value of high TOP2A mRNA expression extending it to the adjuvant treatment setting in early high-risk breast cancer. The strong adverse prognostic impact of high HER2/TOP2A mRNA co-expression needs further validation in studies designed to evaluate markers predictive for anthracyclines.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12611000506998.
Background: NUCKS (Nuclear, Casein Kinase and Cyclin-dependent Kinase Substrate) is a nuclear, DNA-binding and highly phosphorylated protein. A number of reports show that NUCKS is highly expressed on the level of mRNA in several human cancers, including breast cancer. In this work, NUCKS expression on both RNA and protein levels was studied in breast tissue biopsies consisted of invasive carcinomas, intraductal proliferative lesions, benign epithelial proliferations and fibroadenomas, as well as in primary cultures derived from the above biopsies. Specifically, in order to evaluate the level of NUCKS protein in correlation with the histopathological features of breast disease, immunohistochemistry was employed on paraffin sections of breast biopsies of the above types. In addition, NUCKS expression was studied by means of Reverse Transcription PCR (RT-PCR), real-time PCR (qRT-PCR) and Western immunoblot analyses in the primary cell cultures developed from the same biopsies.
Background: Integrins are transmembrane adhesion receptors that provide the physical link between the actin cytoskeleton and the extracellular matrix. It has been well established that integrins play a major role in various cancer stages, such as tumor growth, progression, invasion and metastasis. In breast cancer, integrin alphavbeta3 has been associated with high malignant potential in cancer cells, signaling the onset of widespread metastasis. Many preclinical breast cancer studies are based on established cell lines, which may not represent the cell behavior and phenotype of the primary tumor of origin, due to undergone genotypic and phenotypic changes. In the present study, short-term primary breast cancer cell cultures were developed. Integrin alphavbeta3 localization was studied in correlation with F-actin cytoskeleton by means of immunofluorescence and immunogold ultrastructural localization. Integrin fluorescence intensities were semi-quantitatively assessed by means of computerized image analysis, while integrin and actin expression was evaluated by Western immunoblotting.
IntroductionAdrenal myelolipomas are relatively rare, non-functioning benign tumours composed of mature fatty and active hematopoietic elements. They can be asymptomatic, even if their size is massive. Diagnosis is relatively simple using ultrasound, computed tomography and magnetic resonance imaging. Surgical resection through an extraperitoneal approach is advocated in cases of symptomatic or large myelolipomas exceeding 5-cm in diameter. Their low incidence seems to be increasing from 0.2% to 10% during the last decade.Case presentationWe present a case of a giant adrenal myelolipoma in a 68-year-old Caucasian male, who was presented with left lumbar pain. Renal ultrasound, CT and MRI demonstrated a well demarcated mass, with a maximum diameter of 10-cm. The differential diagnosis comprised the adrenal myelolipoma, the retroperitoneal liposarcoma and the renal angiomyolipoma. Thus, the patient was subjected to a left adrenalectomy.ConclusionMultiple theories have been proposed for the increasing frequency and natural course of the adrenal myelolipoma, with chronic adrenal stimulation and the contemporary stressful lifestyle to be the most appealing. Surgical treatment is advocated through an extraperitoneal approach because of the quicker recovery of the patient and the smaller postoperative complication rate.
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