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2.
Geburtshilfe Frauenheilkd ; 82(1): 85-92, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35027863

ABSTRACT

Objectives Endometriosis is a chronic disease which is diagnosed by surgical intervention combined with a histological work-up. Current international and national recommendations do not require the histological determination of the proliferation rate. The diagnostic and clinical importance of the mitotic rate in endometriotic lesions still remains to be elucidated. Methods In this retrospective study, the mitotic rates and clinical data of 542 patients with histologically diagnosed endometriosis were analyzed. The mean patient age was 33.5 ± 8.0 (17 - 72) years, and the mean reproductive lifespan was 21.2 ± 7.8 (4 - 41) years. Patients were divided into two groups and patients' reproductive history and clinical endometriosis characteristics were compared between groups. The study group consisted of women with confirmed mitotic figures (n = 140, 25.83%) and the control group comprised women without proliferative activity according to their mitotic rates (n = 402, 74.27%). Results Women with endometriotic lesions and histologically confirmed mitotic figures were significantly more likely to have a higher endometriosis stage (p = 0.001), deep infiltrating endometriosis (p < 0.001), ovarian endometrioma (p = 0.012), and infertility (p = 0.049). A mitotic rate > 0 was seen significantly less often in cases with incidental findings of endometriosis (p = 0.031). The presence of symptoms and basic characteristics such as age, age at onset of menarche, reproductive lifespan and parity did not differ between the group with and the group without mitotic figures. Conclusion This study shows that a simple histological assessment of the mitotic rate offers additional diagnostic value for the detection of advanced stages of endometriosis. The possible role as a predictive marker for the recurrence of endometriosis or the development of endometriosis-associated cancer will require future study.

3.
Breast Care (Basel) ; 14(4): 217-223, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31558896

ABSTRACT

BACKGROUND: Prophylactic mastectomies in carriers of mutations in BRCA1 or BRCA2 are becoming increasingly more accepted. We investigated the outcome after prophylactic mastectomy, especially regarding satisfaction with the procedure, in a monocenter study. METHODS: BRCA1/2 mutation carriers and non-carriers with elevated pedigree-based cancer risk were followed prospectively in a structured surveillance program between 2000 and 2017. A retrospective telephone survey was conducted among all patients with documented prophylactic mastectomy. Complications and satisfaction with the decision for prophylactic mastectomy were recorded. RESULTS: 39 patients who opted for a prophylactic mastectomy (38 BRCA1/2 mutation carriers and 1 non-carrier) were interviewed. Mostly nipple-sparing mastectomy with reconstruction was performed (87%). Half of the patients (22/39; 56.4%) had a history of unilateral breast cancer. The median time since prophylactic mastectomy was 5.6 years. While 61.5% did not report any complications, flap loss was seen in 15% (3/20) and moderate limitations in everyday life were present in 20% (7/35). An improvement in quality of life was noticed by 82% after prophylactic mastectomy and no patient expressed regret with regard to the decision. CONCLUSIONS: Prophylactic mastectomy is a procedure with risk for long-term complications in some cases. Our results confirm high satisfaction with the decision and improved quality of life.

4.
Cell Rep ; 27(4): 1103-1118.e6, 2019 04 23.
Article in English | MEDLINE | ID: mdl-31018127

ABSTRACT

Neocortex expansion during mammalian evolution has been linked to an increase in proliferation of basal progenitors in the subventricular zone. Here, we explored a potential role of YAP, the major downstream effector of the Hippo pathway, in proliferation of basal progenitors. YAP expression and activity are high in ferret and human basal progenitors, which exhibit high proliferative capacity, but low in mouse basal progenitors, which lack such capacity. Conditional expression of a constitutively active YAP in mouse basal progenitors resulted in increased proliferation of basal progenitor and promoted production of upper-layer neurons. Pharmacological and genetic interference with YAP function in ferret and human developing neocortex resulted in decreased abundance of cycling basal progenitors. Together, our data indicate that YAP is necessary and sufficient to promote the proliferation of basal progenitors and suggest that increases in YAP levels and presumably activity contributed to the evolutionary expansion of the neocortex.


Subject(s)
Adaptor Proteins, Signal Transducing/physiology , Cell Cycle Proteins/physiology , Neocortex/cytology , Stem Cells/cytology , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Animals , Biological Evolution , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Proliferation , Ferrets , Humans , Mammals , Mice , Neocortex/growth & development , Neocortex/metabolism , Signal Transduction , YAP-Signaling Proteins
5.
Arch Gynecol Obstet ; 295(5): 1227-1238, 2017 May.
Article in English | MEDLINE | ID: mdl-28324225

ABSTRACT

BACKGROUND: Determination of mutation status of BRCA1 and BRCA2 has become part of the clinical routine. However, the spectrum of genetic variants differs between populations. The aim of this study was to deliver a comprehensive description of all detected variants. METHODS: In families fulfilling one of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) criteria for genetic testing, one affected was chosen for analysis. DNA of blood lymphocytes was amplified by PCR and prescreened by DHPLC. Aberrant fragments were sequenced. All coding exons and splice sites of BRCA1 and BRCA2 were analyzed. Screening for large rearrangements in both genes was performed by MLPA. RESULTS: Of 523 index patients, 121 (23.1%) were found to carry a pathogenic or likely pathogenic (class 4/5) mutation. A variant of unknown significance (VUS) was detected in 73/523 patients (13.9%). Two mutations p.Gln1756Profs*74 and p.Cys61Gly comprised 42.3% (n = 33/78) of all detected pathogenic mutations in BRCA1. Most of the other mutations were unique mutations. The most frequently detected mutation in BRCA2 was p.Val1283Lys (13.9%; n = 6/43). Altogether, 101 different neutral genetic variants were counted in BRCA1 (n = 35) and in BRCA2 (n = 66). CONCLUSION: The two most frequently detected mutations are founder mutations in Poland and Czech Republic. More similarities seem to be shared with our direct neighbor countries compared to other European countries. For comparison of the extended genotype, a shared database is needed.


Subject(s)
Breast Neoplasms/genetics , Genes, BRCA1 , Genes, BRCA2 , Mutation , Ovarian Neoplasms/genetics , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Female , Humans
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