Neuroendocrine carcinomas (NECs) of the colorectum are rare but highly aggressive neoplasms. These tumors show some shared genetic alterations with colorectal adenocarcinomas, and most of them have adjacent glandular adenoma or adenocarcinoma components. However, genetic data on colorectal NECs still are sparse and insufficient for definite conclusions regarding their molecular origin. Based on morphological characterization, panel and whole-exome sequencing, we here present results from an in-depth analysis of a collection of 15 colorectal NECs with glandular components, 10 of which by definition were mixed adenoneuroendocrine carcinomas (MANECs). Among shared genetic alterations of both tumor components, we most frequently found TP53, KRAS and APC mutations that also had highest allele frequencies. Mutations exclusive to glandular or neuroendocrine components outnumbered shared mutations but occurred at lower allele frequencies. Our findings not only provide additional evidence for a common clonal origin of colorectal NECs and adjacent glandular tumor components, but strongly suggest their development through the classical adenoma-carcinoma sequence. Moreover, our data imply early separation of glandular and neuroendocrine components during malignant transformation with subsequent independent mutational evolution.

The five-miRNA-signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC.

Current clinical imaging methods face limitations in the detection and correct characterization of different subtypes of renal cell carcinoma (RCC), while these are important for therapy and prognosis. The present study evaluates the potential of grating-based X-ray phase-contrast computed tomography (gbPC-CT) for visualization and characterization of human RCC subtypes. The imaging results for 23 ex vivo formalin-fixed human kidney specimens obtained with phase-contrast CT were compared to the results of the absorption-based CT (gbCT), clinical CT and a 3T MRI and validated using histology. Regions of interest were placed on each specimen for quantitative evaluation. Qualitative and quantitative gbPC-CT imaging could significantly discriminate between normal kidney cortex (54 ± 4 HUp) and clear cell (42 ± 10), papillary (43 ± 6) and chromophobe RCCs (39 ± 7), p < 0.05 respectively. The sensitivity for detection of tumor areas was 100%, 50% and 40% for gbPC-CT, gbCT and clinical CT, respectively. RCC architecture like fibrous strands, pseudocapsules, necrosis or hyalinization was depicted clearly in gbPC-CT and was not equally well visualized in gbCT, clinical CT and MRI. The results show that gbPC-CT enables improved discrimination of normal kidney parenchyma and tumorous tissues as well as different soft-tissue components of RCCs without the use of contrast media.

BackgroundPostoperative (chemo) radiation improves tumor control and survival in high-risk patients with head and neck squamous cell carcinoma based on established risk factors. The clinical cooperation group “Personalized Radiotherapy in Head and Neck Cancer” focuses on the identification and validation of new biomarkers, which are aimed at eventually stratifying and personalizing the therapy concept. Hence, we reviewed all patients with head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx, treated with postoperative (chemo) radiation from 06/2008 until 06/2015 at the Department of Radiation Oncology in the University Hospital, LMU Munich. Here we report the clinical results of the cohort, laying the foundation for further research within the framework of a clinical cooperation group.MethodsPatient data were retrospectively (until 2013) and prospectively (from 2013) collected and analyzed for outcome and treatment failures with regard to previously described and established risk factors.ResultsWe identified 302 patients (median follow-up 45 months, average age 60.7 years), having received postoperative (chemo)radiation (median 64 Gy). Chemotherapy was added in 58% of cases, mostly Cisplatin/5- Fluorouracil in concordance with the ARO 96–3 study. The 3-year overall survival, local, locoregional and distant failure estimates were 70.5, 9.7, 12.2 and 13.5%, respectively. Human papillomavirus-associated oropharyngeal cancer was associated with a significant improved overall survival, locoregional, distant and overall tumor control rates in multivariate analysis. Additionally, in multivariate analysis, for local failure, resection status and perineural invasion, for locoregional and distant failure extracapsular extension and for overall survival the presence of nodal disease were significant adverse factors. Moreover, 138 patients have been treated in concordance with the ARO 96–3 protocol, corroborating the results of this study.ConclusionsOur cohort represents a large unselected cohort of patients with head and neck squamous cell carcinoma treated with postoperative (chemo)radiation. Tumor control rates and survival rates are consistent with the results of previously reported data.