Microenvironment-induced restoration of cohesive growth associated with focal activation of P-cadherin expression in lobular breast carcinoma metastatic to the colon.

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E-cadherin loss. Focal activation of P-cadherin expression in tumor cells that are deficient for E-cadherin occurs in a subset of ILCs. Switching from an E-cadherin deficient to P-cadherin proficient status (EPS) partially restores cell-cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52-year-old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E-cadherin and P-cadherin. CDH1/E-cadherin mutations were determined by next-generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1/E-cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E-cadherin-negative and P-cadherin-negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter-cryptal ILC cells switched to a P-cadherin-positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment-induced EPS and conversion to cohesive growth.

Malignant phyllodes tumor and invasive lobular breast carcinoma: Morpho-molecular characterization of an uncommon collision tumor and review of the literature.

Phyllodes tumor (PT) of the breast is a biphasic neoplasia composed of mesenchymal and epithelial cells. PTs are graded as benign, borderline or malignant according to histological criteria. Invasive lobular carcinoma (ILC) is a special breast cancer subtype defined by non-cohesive growth and loss of E-cadherin. PT is treated by resection. ILC is treated by resection and adjuvant endocrine therapy with or without chemotherapy. Collision tumors composed of PT and concurrent ILC are rare. Due to their dissociated growth, ILC cells may escape histologic detection when admixed with PTs. Here we report the case of a 71-years-old female diagnosed with a PT/ILC collision tumor. The patient presented with a tumor in the right breast. A core needle biopsy showed mesenchymal spindle cell proliferates suspicious for a PT. The resection specimen confirmed a malignant PT with stromal overgrowth. Unexpectedly, the resection specimen also revealed sparse infiltrates of ILC admixed with the PT. Immunohistochemistry of mesenchymal PT cells and ILC cells was consistent with the histomorphological diagnosis. Molecular analyses demonstrated a IDH1 variant of unknown significance and GNAS gene mutation in microdissected PT tissue. ILC tissue showed wild-type IDH1 and GNAS, but harbored CDH1/E-cadherin and TP53 gene mutations, arguing against clonal relatedness of the two lesions. Review of the literature identified six reported PT/ILC collision tumors, involving three benign, two borderline and one malignant PT. In summary, this is the second report on a malignant PT/ILC collision tumor. Correct histologic diagnosis of PT/ILC collision tumors is clinically relevant, because adjuvant endocrine therapy is mandatory for ILC.

Effects of Recreational Therapy and 3D Ultrasonography for High-Risk Pregnancies on Psychological Well-Being during Hospitalization and in the Puerperal Phase.

Hospitalization during pregnancy often produces psychosocial distress for pregnant women. In this study, 3D ultrasound and recreational therapy were compared to the standard treatment for their influence on depressive symptoms and anxiety. In this prospective one-year intervention study, women who were admitted to the hospital for any pregnancy complication, other than psychiatric, were included. A control group, with standard clinical treatment, and two intervention groups, both additionally receiving either 3D ultrasound or recreational therapy, were established. Psychological well-being was assessed at defined times by the PHQ-health-questionnaire. A total of 169/211 women were included: control group n = 79, 3D ultrasound group n = 43, and crochet group n = 83. A higher than estimated underlying depression was seen for all women on admission. The intervention groups showed less depression (p = 0.02762). No difference was seen between the intervention groups (p = 0.23029). Anxiety decreased throughout intervention, but not significantly. On admission, all women showed similar results of underlying depression, indicating that hospitalization itself already causes mild psychological stress. Both interventions decreased depressive symptoms. Intervention with either recreational therapy or 3D ultrasound can prevent the development of mild and major depression and decrease anxiety disorders, and therefore has a positive effect on well-being during hospitalization. These results emphasize the need to implement forms of interventions to improve the well-being of women, as this might improve pregnancy and neonatal outcome.

[What is confirmed in the prevention, diagnostics and treatment of early breast cancer?] / Was ist gesichert in der Prävention, Diagnostik und Therapie des frühen Mammakarzinoms?

With more than 2.3 million newly diagnosed cases worldwide in 2020, breast cancer is still the most frequent cancer in women and despite improved diagnostics and treatment the most frequent cause of death from cancer. Continuous scientific developments in the areas of prevention, the application of modern diagnostic procedures and treatment options for early breast cancer, have led to an improvement in the 5­year probability of survival. The treatment of early breast cancer is based on a combination of a locoregional and a systemic treatment approach. Depending on the tumor stage and the histological subtype the application of neoadjuvant chemotherapy with or without antibodies or immunotherapy is necessary. This article gives an overview of the current standard in the diagnostics and treatment of early breast cancer, without giving an in-depth elucidation of the differentiated subtype-specific systemic treatment. For this, reference should be made to the relevant literature.

First Prospective Cross-Sectional Study on the Impact of Immigration Background and Education in Early Detection of Breast Cancer.

BACKGROUND: Although immigrant health is an important issue in national health policy, there is a serious shortage of data in many countries. Most studies lack information on educational status, which is a major limitation. This prospective cross-sectional study analyzed a real-world breast cancer population on the influence of immigration background and educational status on participation in breast cancer early detection programs in the federal state of Lower Saxony, Germany. METHODS: Data collection was conducted from 2012 to 2016 in six certified breast cancer centers using a standardized questionnaire for patients' interview and tumor-specific data from the patients' medical records. RESULTS: 2,145/3,047 primary breast cancer cases were analyzed. 17.5% of our patients had a history of immigration, including n = 202 first-generation immigrants and n = 168 second-generation immigrants. Most of them were citizens of EU27 member states. No significant difference was seen in age, tumor stage, histology, grading, Ki-67, Her2/neu-status, and hormone receptor status compared to the native cohort. 100% participation rate in the breast cancer early detection programs were seen in patients with no school graduation. With regards to the national mammography screening program, participation decreased significantly with educational status (p = 0.0003). CONCLUSIONS: No tumor biological differences were seen between immigrants and German natives. In first-generation immigrants, early detection programs were well accepted despite sociocultural and language differences. Participation rate decreased significantly with higher education levels irrespective of country of origin. Immigration background does not have a negative effect on the participation in breast cancer screening. This mainly relates to immigrants from EU27 member states.

Quality of Life after Bilateral and Contralateral Prophylactic Mastectomy with Implant Reconstruction.

BACKGROUND: Prophylactic mastectomy is an effective approach to breast cancer risk reduction in patients at high risk. Further studies using standardized measures for quality of life are needed to better understand the effect of prophylactic mastectomy on individual patients and, thereby, allow for better patient counseling and selection. METHODS: In this prospective study patients undergoing bilateral mastectomy were asked to complete the BREAST-Q questionnaire before and 1 year after surgery. All patients underwent bilateral mastectomy with implant-based breast reconstruction. Patient- and surgery-related information was collected in a database. RESULTS: In total, 48 patients underwent bilateral skin-sparing mastectomy. Of these, 29 (60.4%) suffered from breast cancer. A 2-stage reconstruction with intermediate expander implantation was conducted in 19 (39.6%) patients. All patients completed the BREAST-Q questionnaire. The domain "psychosocial well-being" was significantly improved from a mean score of 74.98 preoperatively to a postoperative score of 81.56 (p = 0.021). In contrast, the domain "physical well-being" dropped -8.38 points on average to a postoperative score of 74.96 (p < 0.001). Interestingly, patients with the lowest preoperative score in the domain "satisfaction with breast" showed the greatest increase after surgery (50.31 vs. 67.25, p < 0.001). On the contrary, patients with the highest preoperative values experienced the strongest decrease in satisfaction (91.60 vs. 75.27, p = 0.012). CONCLUSION: Implant-based prophylactic mastectomy leads to good quality-of-life results in patients at high risk for breast cancer. Especially, patients with a low preoperative satisfaction with their breasts have a significantly higher chance of experiencing substantial improvements in their quality of life.

Peritoneal contamination with ICG-stained cervical secretion as surrogate for potential cervical cancer tumor cell dissemination: A proof-of-principle study for laparoscopic hysterectomy.

INTRODUCTION: Intracorporal colpotomy during radical hysterectomy for cervical cancer is discussed to be a risk factor for peritoneal dissemination of tumor cells. It might lead to increased recurrence rates after laparoscopic radical hysterectomy compared with abdominal hysterectomy, as shown by the recent LACC study. Data on the frequency or mechanisms of peritoneal contamination are missing. We aimed to analyze peritoneal contamination of cervical secretion during intracorporal colpotomy with a novel indocyaningreen (ICG)-based technique. MATERIAL AND METHODS: In this prospective proof-of-principle study, patients undergoing routine laparoscopic or robot-assisted hysterectomy were selected. ICG was specifically applied to the cervical surface and routine surgery was performed. During colpotomy, pictures under white and fluorescence light were taken to evaluate frequency of contamination. RESULTS: By using cervically applied ICG we were able to visualize directly peritoneal contamination with cervical secretion during intracorporal colpotomy. We detected peritoneal contamination in 9/12 (75%) patients undergoing routine laparoscopic hysterectomy. Contamination of laparoscopic instruments occurred in 60% of the patients. When contamination occurred, it was routinely detectable during all steps of colpotomy. There were no adverse effects during surgery. CONCLUSIONS: Peritoneal contamination with cervical secretion frequently occurs during intracorporal colpotomy. This novel technique represents a promising tool for feasible and direct visualization of peritoneal contamination during colpotomy. The technique may be easily implemented in further studies on laparoscopic and abdominal hysterectomy and serve as a quality assessment tool for surgeons and surgical techniques.

Neonatal and Maternal Short-Term Outcome Parameters in Instrument-Assisted Vaginal Delivery Compared to Second Stage Cesarean Section in Labour: A Retrospective 11-Year Analysis.

BACKGROUND: This study is aimed at comparing the neonatal and maternal short-term outcomes after instrumental-assisted vaginal delivery and cesarean section (CS) in labour. METHODS: This retrospective study over a period of 11 years included singleton pregnancies above 34 + 0 gestational weeks, giving birth either by instrumental-assisted delivery or CS in labour. Maternal and neonatal outcome parameters were analysed using t test or linear regression. RESULTS: A total of 1,971/2,571 deliveries were included for analysis: 149 forceps-, 393 vacuum-assisted deliveries and 1,420 CS in labour. Regarding maternal outcome, the rate of severe anaemia and hemorrhage in women who delivered by CS in labour was lower than in instrumental-assisted delivery. Analysis of neonatal outcome parameters showed a lower cord pH <7.20 in CS; however, 5-min Apgar score and the need for intervention did not differ with the mode of delivery. The mode of anaesthesia affected the neonatal recovery rate. Subanalysis within instrumental deliveries showed reduced rates of vaginal tears, but higher rates of episiotomy in forceps-assisted deliveries. Except for higher rates of cephalhaematomas after ventouse, no differences were detected regarding further neonatal outcome measures. CONCLUSION: Assuming that indication and application is correct, vaginal instrumental-assisted delivery can be considered as an alternative delivery mode to second stage CS in labour.

[Intrapartum Translabial Ultrasound: A Systematic Analysis of The Fetal Head Station in The First Stage of Labor]. / Ultraschall unter der Geburt: Eine systematische Analyse des Höhenstandes des kindlichen Kopfes in der Eröffnungsperiode der Geburt.

INTRODUCTION: This prospective study aimed to define the angle of progression (AOP) in relation to the height position of the fetal head during the first stage of labour. It was investigated if it is possible to predict the mode of delivery or the duration of labour by AOP. METHODS: Influencing factors on delivery were head circumference, birth-weight, administration of oxytocin, epidural anaesthesia (EA) and parity, and their impact on AOP was analysed. AOP was calculated using three different formulas. Inclusion criteria were vaginal delivery of singletons in cephalic, occipito-anterior presentation. RESULTS: 30/80 recruited women met the study criteria. 90% delivered spontaneously vaginally, 10% had instrument-assisted vaginal delivery. The average AOP in spontaneous vaginal deliveries was 100.9° at cervical dilation less than 5 cm, and 125.3° at cervical dilatation more than 5 cm. The average AOP in instrument-assisted births was 93° and 113.9° when the cervical os was less than 5 cm and more than 5 cm, respectively. Analysis identified a predictive trend towards the duration of labour only by use of the first AOP formula but not regarding the mode of delivery. CONCLUSION: Sonographically assessed AOP during first stage of labour indicates trends regarding the duration of labour.

Lobular carcinoma in situ and invasive lobular breast cancer are characterized by enhanced expression of transcription factor AP-2ß.

Transcription factor AP-2ß (TFAP2B) regulates embryonic organ development and is overexpressed in alveolar rhabdomyosarcoma, a rare childhood malignancy. Gene expression profiling has implicated AP-2ß in breast cancer (BC). This study characterizes AP-2ß expression in the mammary gland and in BC. AP-2ß protein expression was assessed in the normal mammary gland epithelium, in various reactive, metaplastic and pre-invasive neoplastic lesions and in two clinical BC cohorts comprising >2000 patients. BCs from various genetically engineered mouse (GEM) models were also evaluated. Human BC cell lines served as functional models to study siRNA-mediated inhibition of AP-2ß. The normal mammary gland epithelium showed scattered AP-2ß-positive cells in the luminal cell layer. Various reactive and pre-invasive neoplastic lesions, including apocrine metaplasia, usual ductal hyperplasia and lobular carcinoma in situ (LCIS) showed enhanced AP-2ß expression. Cases of ductal carcinoma in situ (DCIS) were more often AP-2ß-negative (P<0.001). In invasive BC cohorts, AP-2ß-positivity was associated with the lobular BC subtype (P<0.001), loss of E-cadherin (P<0.001), a positive estrogen receptor (ER) status (P<0.001), low Ki67 (P<0.001), low/intermediate Oncotype DX recurrence scores (P<0.001), and prolonged event-free survival (P=0.003). BCs from GEM models were all AP-2ß-negative. In human BC cell lines, AP-2ß expression was independent from ER-signaling. SiRNA-mediated inhibition of AP-2ß diminished proliferation of lobular BC cell lines in vitro. In summary, AP-2ß is a new mammary epithelial differentiation marker. Its expression is preferentially retained and enhanced in LCIS and invasive lobular BC and has prognostic implications. Our findings indicate that AP-2ß controls tumor cell proliferation in this slow-growing BC subtype.