ABSTRACT
BACKGROUND: Technical advancement and availability of high-throughput analysis has advanced molecular subtyping of most cancers. Thus, new possibilities for precision oncology have emerged. AIM: Therefore, we aimed to collect data regarding availability and use of next generation sequencing (NGS) for urothelial cancer within the uropathology working group of the German Society of Pathology. METHODS: We collected data by questionnaires and additionally asked for sequencing results of bladder cancers in the participating institutions. RESULTS: A total of 13 university-affiliated institutes of pathology took part in the survey. All university institutes offer NGS-based molecular panel diagnostics and provide panels covering between 15 and 170 genes. Altogether, only 20 bladder cancers were sequenced in routine diagnostics and for 10 cancers potential targeted treatment options were available. DISCUSSION: So far, despite availability of NGS diagnostics at university institutes of pathology, only few bladder cancer samples have been sequenced. Based on current data from the molecular subtyping of bladder cancers, we recommend a step-by-step protocol with basic immunohistochemistry analysis and subsequent subtype-dependent analyses, e.g., alterations of the fibroblast growth factor receptors (FGFR) or comprehensive gene panel analyses.
Subject(s)
High-Throughput Nucleotide Sequencing , Precision Medicine , Humans , Mutation , Pathology, Molecular , Surveys and Questionnaires , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathologyABSTRACT
Fetus acardius amorphus is a rare congenital malformation characterized by the lack of a functional heart, the presence of a bivascular umbilical cord, as well as a developed and organized skeletal system and partially organized inner organs. Fetus acardii mostly occur in multiple gestations. The pathogenesis of this entity is not clarified yet. It has been hypothesized that, although formation of anastomosing vessels between the co-twin and the anomalous embryo as well as reverse directed blood flow within the umbilical arteries of the weaker twin may allow sufficient blood flow to form rudimentary internal organs, it is insufficient to develop a fully functional heart. We had a case of fetus acardius amorphus, where we performed autopsy as well as routine histology assessment to identify different types of tissues. We showed that our fetus acardius amorphus demonstrated histomorphological features of renal tubular dysgenesis, confirmed by lack of proximal tubules, extramedullary hematopoiesis and increased number of smooth muscle actin positive vessels. This is a novel finding and has not been reported previously.
ABSTRACT
Precision oncology is obtaining a central role in the therapy of malignant diseases. The indication for targeted therapy is based on the identification of molecular targets for which next-generation sequencing (NGS) is commonly used nowadays. All approved predictive biomarkers and molecular targets, including gene fusions and copy number alterations, can be identified depending on panel design and method applied. Some clinical scenarios, however, may require more holistic genomic approaches, such as whole-genome/whole-exome and transcriptome analysis, which must be embedded in a clinical trial. Here, key aspects and applications of each method are summarized and discussed.
Subject(s)
Genomics , Neoplasms , Biomarkers, Tumor , High-Throughput Nucleotide Sequencing , Humans , Mutation , Neoplasms/genetics , Neoplasms/pathology , Precision MedicineABSTRACT
The field of gastrointestinal oncology is rapidly developing, on the one hand through the identification of novel molecular targets and therapeutic principles, on the other hand through the establishment and improvement of multidisciplinary treatment strategies. The following manuscript summarizes the most important trial results of the ASCO Meeting 2015 for gastrointestinal cancers. Besides trials on perioperative treatment of esophageal-, pancreatic- and colon cancer, we will present impressive data on new therapeutic strategies such as immunotherapy in gastric-, liver and microsatellite instable colorectal cancer. The trials will be put into context by the authors.
Subject(s)
Biomedical Research/trends , Clinical Trials as Topic , Gastroenterology/trends , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/therapy , Medical Oncology/trends , Evidence-Based Medicine , Humans , Societies, MedicalABSTRACT
The incidence of colorectal cancer worldwide is higher in men. Risk factors like smoking, overweight, or dietary exposures cannot explain this gender difference. In the pathogenesis of colorectal carcinoma, estrogen seems to play an important protective role. Estrogen may reduce the risk of developing colon cancer in premenopausal women. The expression of estrogen receptor ß in healthy colon is significantly decreased in the development of colon cancer. The role of estrogen in pathogenic pathways is most likely protective or might serve as a tumor suppressor. However, the exact role of estrogen in the carcinogenesis of colorectal cancer still remains unclear. Furthermore, tumor localization depends on age and gender. Therefore, in postmenopausal women there is a shift to predominantly right-sided cancers. Here, a link between tumor localization and MSI-H (microsatellite-high) status can be assumed. There are virtually no prospective randomised trials in adjuvant or palliative therapy of patients with colorectal cancer. Earlier data from registries point to a better post-operative survival of women, while men seem to benefit more from adjuvant therapy. Potentially, there may be a role of an increased toxicity to 5-FU in women. In the palliative setting, there are also only few gender-specific analyses. Women with right-sided colon cancers show a significant worse response and survival under an anti-EGFR antibody treatment compared with men and left-sided cancers. A focus on gender-specific differences should be incorporated more often in future randomised trials.
