[Predicting response to therapy in breast cancer]. / Vorhersage des Therapieansprechens beim Mammakarzinom.

Molecular staging of breast cancer with microarray technologies leads to different gene expression profiles distinguishing 4 special groups: luminal A and B subtype, HER2 subtype and basal subtype. These 4 groups show a different prognosis as well as different behaviours and responses to adjuvant therapy. The development of gene expression profiles to classify breast cancer may contribute to the targeted institution of adjuvant therapies. Especially the 21-gene recurrence score (Oncotype DX) and the 70-gene profile (Mamma-print) have become intensively examined prognostic and predictive tools. As chemotherapy is an integral component of adjuvant therapy in early breast cancer but estrogen-receptor-positive breast cancer is the most common type, patient selection for adjuvant chemotherapy is of particular interest. In instances when the benefit from chemotherapy seems modest, there is a decision making tool beside traditional histopathological parameters that might provide additional objective prognostic and predictive information. Those genomic decision making approaches may yield more rational treatment choices and may keep patients from systemic treatment modalities of lower value.

[Clinical impact of fetal MRI in addition to ultrasonography in brain anomalies--three case reports]. / Klinische Bedeutung der MRT in Ergänzung zur Sonografie bei fetalen Hirnfehlbildungen--drei Fallberichte.

Fetal magnetic resonance imaging (MRI) is a reliable method to further evaluate brain anomalies detected on ultrasonography. MRI can reveal additional brain abnormalities which are consequential for counselling parents about the fetal prognosis and subsequently influence the decision about continuing the pregnancy. In case of fatal malformations, MRI can confirm a diagnosis established on ultrasonography, supplying more reliability.

Ultrasound-guided large-core needle biopsies of breast lesions: analysis of 962 cases to determine the number of samples for reliable tumour classification.

The objective of this one-institutional study was to determine the number of large-core needle biopsies (LCNB), under three-dimensional ultrasound (3D-US) validation, that are sufficient to obtain a reliable histological diagnosis of a sonographically detectable breast lesion. Over an 28-month period, 962 sonographically guided LCNB were performed under 3D-US validation to assess 962 breast lesions. All biopsies were carried out with an automated core biopsy device fitted with 14-gauge (22 mm excursion) needles. Data of 962 biopsied breast lesions were gathered. Surgical follow-up was available for 659 lesions. Breast malignancies were diagnosed by ultrasound-guided LCNB with a sensitivity of 98.2% by performing three cores per lesion. In few cases, the open surgical specimen revealed the presence of invasive carcinomas in contrast to initial LNCB-based classification as ductal carcinomas in situ (DCIS, 11 lesions), lobular carcinoma in situ (one lesion), and atypical ductal hyperpasia (one lesion). Owing to disagreement between classification based on breast-imaging and histological findings, eight of these tumours were subsequently excised. Of the lesions that were removed at the patients' requests despite benign LCNB diagnosis, two were infiltrating carcinoma and one a DCIS. We demonstrate that three 3D-US-guided percutaneous core specimens are sufficient to achieve tissue for a reliable histological assessment of sonographically detectable breast lesions and allow the detection of malignancies with high sensitivity and low rate of false-negative diagnoses.

Down-regulation of insulin-like growth factor-I receptor and insulin receptor substrate-1 expression in advanced human breast cancer.

The ligands, receptors and related signaling proteins of the insulin-like growth factor family are involved in the regulation of breast-cancer cell growth. We investigated the expression pattern of insulin-like growth factor-I receptor (IGF-IR), insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), a core downstream signaling protein, in 69 primary breast-cancer specimens of different grades and in 21 control tissues by immunohistochemistry. In addition, cell proliferation (percentage of Ki67(+) nuclei) and estrogen receptor (ER) expression were determined. IGF-IR, IRS-1 and IR were expressed mainly in epithelial cells. IRS-1 and IGF-IR were expressed at high levels in control tissues and in well and moderately differentiated carcinomas but at low levels in poorly differentiated breast cancers. IR expression did not show a significant correlation with the differentiation grade of the tissues investigated. Statistical analysis (ROC analysis for tumor grade) demonstrated that down-regulation of IGF-IR and IRS-1 correlated better with tumor progression than reduction of ER expression or increase in cell proliferation, IGF-IR showing the best correlation, followed by IRS-1 and, less significant, ER and Ki67. Our findings clearly show that progression of breast cancer is accompanied by a reduction of IGF-IR/IRS-1 expression and that IGF-IR/IRS-1 expression inversely correlates with high proliferation rate in dedifferentiated breast cancers. The strong correlation of IGF-IR and IRS-1 down-regulation with tumor progression suggests the use of IGF-IR and IRS-1 as a novel set of marker proteins for tumor grading.

[Examination of gallstones on their surface and in fractured cross sections by incident light microscopy and scanning electron microscopy (author's transl)]. / Untersuchungen an Oberflächen und Bruchflächen von Gallensteinen mit dem Licht- und Rasterelektronenmikroskop

Operatively removed gallstones were examined on their surfaces and in fractured cross sections by incident light microscopy and scanning electron microscopy. In addition, micro-bore samples and X-ray crystallography were done. Five gallstone types consisting of three basic structural layers are differentiable by incident light microscopy. The three layers consist of a central nucleus which is always present, a radially structured middle layer, and a fine crystalline outer shell, the presence or absence of the latter two layers differentiating the stone types. Two crystal structures could be differentiated by electron microscopy; a flat and a globular type. The nucleus is always of the globular crystalline type, while the outer layers are flat crystalline. From this we were lead to believe that the conditions in vivo, under which the different layers of a gallstone are built, change. The micro-bore samples lead us to believe that calcium is only secondarily layed down in the gallstone framework. White crystalline deposits, which were formed several seconds after fracture, were discovered on the fractured gallstone cross sections.