Anton Scharl

Qualitative [18F]FDG positron emission tomography in primary breast cancer: clinical relevance and practicability

Positron emission tomography (PET) using fluorine-18 2-deoxy-2-fluoro-d-glucose (FDG) is of potential value for the diagnosis of malignant tumours. The aim of this study was to evaluate the use of FDG PET in patients with breast tumours, appraising its applicability in visualising primary carcinomas and regional metastases in a clinical setting. Results of FDG PET were compared with those of mammography, breast ultrasonography and histology in 30 patients with inconclusive breast findings. For PET, transmission and emission images were taken in one or two scan positions, depending on the available time and the clinical status of patients. PET showed focal FDG uptake with high contrast in 21 of 23 primary carcinomas. In one patient, only PET correctly visualized multifocal disease (three foci, Ø 0.4–1 cm). The accuracy of PET in the detection of primary breast cancer was 90%, and in the detection of involved axillary lymph nodes, 94%. All metastases (lymph nodes, lungs, bones, soft tissues) covered by the field of view and demonstrated by other methods (X-ray, computed tomography, magnetic resonance imaging, bone scan) showed FDG uptake. In three patients, only PET initiated further diagnostic procedures. The results indicate that FDG PET can provide a rapid diagnostic study (45–60 min) and allows accurate tumour staging of several organ systems for primary tumour and metastases with a single imaging study in a routine clinical setting.

Detection of squamous cell carcinoma antigen in normal squamous epithelia and in squamous cell carcinomas of the uterine cervix.

Squamous cell carcinoma (SCC) antigen is a subfraction of tumor antigen TA‐4 isolated from a cervical squamous cell carcinoma. The specificity of SCC antigen and the factors influencing its release into serum were evaluated. Antigen concentrations were measured in 157 tissue extracts and in 188 sera of patients with nonmalignant or malignant gynecologic diseases. A commercial radioimmunoassay based on polyclonal antibodies (Abbott Laboratories, North Chicago) was used. Cytosol concentrations were significantly higher (P < 0.005) in normal squamous epithelia (x̃ = 6040 ng/mg cell protein [CP]) and in squamous cell carcinomas (x̃ = 2483 ng/mg CP) of the exocervix than those in normal columnar epithelia and in adenocarcinomas of the endocervix, endometrium, ovary, and breast (x̃ = 1–508 ng/mg CP). Despite the high antigen concentrations in normal squamous epithelia, elevated serum levels (>2.5 ng/ml) were almost exclusively found in patients with cervical squamous cell carcinomas. The sensitivity of SCC antigen as a marker for primary carcinomas was 61%, increasing from 29% in Stage I to 89% in Stage IV. The positivity rate was higher in women with well‐differentiated (78%) and moderately differentiated carcinomas (67%) than in those with poorly differentiated tumors (38%). The results show that SCC antigen is not tumor specific. The release into serum is independent of local tissue content, but is apparently influenced by the infiltrative growth, the mass, and the degree of histologic differentiation of the tumor.

Molecular classification of breast cancer patients by gene expression profiling.

For many tumuors, pathological subclasses exist which have to be further defined by genetic markers to improve therapy and follow‐up strategies. In this study, cDNA array analyses of breast cancers have been performed to classify tumuors into categories based on expression patterns. Comparing purified normal ductal epithelial cells and corresponding tumour tissues, the expression of only a small fraction of genes was found to be significantly changed. A subset of genes repeatedly found to be differentially expressed in breast cancers was subsequently employed to perform a classification of 82 normal and malignant breast specimens by cluster analysis. This analysis identifies a subgroup of transcriptionally related tumours, designated class A, which can be further subdivided into A1 and A2. Correlation with classical clinicopathological parameters revealed that subgroup A1 was characterized by a high number of node‐positive tumours (14 of 16). In this subgroup there was a disproportionate number of patients who had already developed distant metastases at the time of diagnosis (25% in this subgroup, compared with 5% among the rest of the samples). Taken together, the use of these differentially expressed marker genes in conjunction with sample clustering algorithms provides a novel molecular classification of breast cancer specimens, which facilitates the identification of patients with a higher risk of recurrence. Copyright

13th St. Gallen International Breast Cancer Conference 2013: Primary Therapy of Early Breast Cancer Evidence, Controversies, Consensus - Opinion of a German Team of Experts (Zurich 2013)

The International Consensus Conference on the treatment of primary breast cancer takes place every two years in St. Gallen, Switzerland. The panel in St. Gallen is composed of international experts from different countries. From a German perspective, it seems reasonable to interpret the voting results in the light of AGO-recommendations and S3-guidelines for everyday practice in Germany. Consequently, a team of eight breast cancer experts, of whom two are members of the international St. Gallen panel, commented on the voting results of the St. Gallen Consensus Conference (2013). The main topics at this years St. Gallen conference were surgical issues of the breast and axilla, radio-therapeutic and systemic treatment options, and the clinical relevance of tumour biology. The clinical utility of multigene assays for supporting individual treatment decisions was also intensively discussed.

AGO Recommendations for Diagnosis and Treatment of Patients with Advanced and Metastatic Breast Cancer: Update 2013

Every year the Breast Committee of the Arbeitsgemeinschaft Gynakologische Onkologie (German Gynecological Oncology Group, AGO), a group of gynecological oncologists specialized in breast cancer and interdisciplinary members specialized in pathology, radiologic diagnostics, medical oncology, and radiation oncology, prepares and updates evidence-based recommendations for the diagnosis and treatment of patients with early and metastatic breast cancer. Every update is performed according to a documented rule-fixed algorithm, by thoroughly reviewing and scoring the recent publications for their scientific validity and clinical relevance. This current publication presents the 2019 update on the recommendations for metastatic breast cancer.

Immunohistochemical study of distribution of estrogen receptors in corpus and cervix uteri

SummaryAn immunohistochemical assay based on monoclonal antiestrophilin antibodies has been used to localize estrogen receptor (ER) in frozen sections of normal human endometrial, myometrial and cervical tissues from menstruating, hormonally treated, pregnant and postmenopausal women. Specific staining was confined to the cellular nuclei. In proliferative phase endometrium, postmenopausal emdometrium, and endometrium from patients treated with hormone ERs were easily detected in most glandular and stromal cells. After ovulation and in early pregnancy a quick and distinct decrease of ER expression was noted. This was especially the case with the more superficial layers of endometrium (endometrium functionals), the majority of whose cells had either weak localization of ER or none at all. In the endometrium basalis, however, the reduction of ER localization turned out to be more moderate. More then half of the epithelial and stromal cells displayed nuclear staining, partly strong. The myometrium of the corpus uteri showed a similar ER localization and dependence on hormonal stage when compared with the endometrium functionalis. The endocervical mucosa displayed a high degree of ER expression in the proliferative phase in postmenopausal women and in women who had been treated with hormones. Unlike the endometrium and myometrium, the endocervical glands underwent minimal changes in nuclear ER content during the menstrual cycle. Although the endocervical stroma showed cyclic alterations in ER levels, their reduction after ovulation was less marked than in the corresponding endometria. In cervical squamous epithelium ER localization was predominantly confined to the basal layers. In the course of cellular maturation, specific nuclear staining vanished. In the proliferative phase, after the menopause and in early pregnancy, the basal, parabasal and intermediate cells were specifically stained. In the postovulatory phase. However, nuclear staining was confined to the basal and parabasal cells. Hormonally treated squamous epithelia almost completely lacked nuclear ER localization.

14th St. Gallen International Breast Cancer Conference 2015: Evidence, Controversies, Consensus - Primary Therapy of Early Breast Cancer: Opinions Expressed by German Experts

The key topics of this years 14th St. Gallen Consensus Conference on the diagnosis and therapy of primary breast cancer were again questions about breast surgery and axillary surgery, radio-oncology and systemic therapy options in consideration of tumor biology, and the clinical application of multigene assays. This year, the consensus conference took place in Vienna. From a German perspective, it makes sense to substantiate the results of the vote of the international panel representing 19 countries in light of the updated national therapy recommendations of the AGO (Arbeitsgemeinschaft Gynäkologische Onkologie). Therefore, 14 German breast cancer experts, 3 of whom are members of the International St. Gallen Panel, have commented on the voting results of the St. Gallen Consensus Conference 2015 in relation to clinical routine in Germany.

gastric cancer during early pregnancy two case reports

We report two cases of advanced gastric carcinoma in pregnancy.

AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2014

vant decision making. According to ASCO-CAP guidelines, discordances for central versus local immunohistochemical staining of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) are reported in about 20%, major discrepancies in grading for 40% [3–5]. Furthermore, in 2012, Mirror trialists reported an upgrade of 22% of pN0 cases to pN1 in central pathology [6]. In the context of these data, and because of the lack of consideration of HER2 overexpression as a prognostic and predictive factor, the AGO guidelines have downgraded the available version 8.0 of Adjuvant! online (LoE 2bB; AGO+/–). Considering immunohistochemical tumour markers, Ki-67 is a reliable prognostic factor especially after neoadjuvant chemotherapy (NACT)/ short-term endocrine treatment. Data for prediction of chemotherapy outcome are less convincing. The committee nevertheless recommends the clinical use of Ki-67 under the prerequisite of meticulous quality control (LoE 1aA; AGO+). As long as nationwide standardization and quality assurance are not implemented, cut-off levels cannot be reliably defined for routine use. uPA/PAI was tested in prospective trials and is suggested as a reliable prognostic marker and a predictive marker for the usefulness of chemotherapy in N0 cases (LoE 1aA; AGO+). New molecular tools (mRNA, DNA level) have the advantage of higher accuracy, reproducibility and lower interobserver variability compared to IHC. To allow for adequate evaluation of available molecular markers/genomic signatures, Introduction

Immunohistochemical detection of H-ras protooncoprotein p21 indicates favorable prognosis in node-negative breast cancer patients.

We tested primary breast carcinoma tissues from 297 patients using a monoclonal antibody (clone 235-1.7.1.) for the expression of p21ras. 58% of tumors were p21ras-positive. When calculated in a univariate fashion, p21 expression correlated with proliferation activity (proliferating cell nuclear antigen) only. Using the log-rank test (median observation time 94 months) a significantly worse prognosis (disease-free survival, overall survival) relation was found with larger tumors, nodal involvement, anaplasia, rising proliferation activity, and lack of steroid receptors. Detection of p21ras correlated with a more favorable prognosis but only in node-negative patients. Stepwise correlation according to the Cox hazard model ranked p21 expression as a most significant predictor of prognosis second only to nodal status. These data suggest that detection of p21ras indicates the presence of a parameter which may act as tumor suppressor and benefit patients’ survival.