<i>ERBB2</i> Amplification as a Predictive and Prognostic Biomarker in Upper Tract Urothelial Carcinoma

Upper tract urothelial carcinomas (UTUCs) occur in about 5–10% of all urothelial carcinomas and are frequently discovered in high-stage disease. We aimed to evaluate human epidermal growth factor receptor 2 (ERBB2) protein expression immunohistochemically and ERBB2 amplification in UTUCs by fluorescence in situ hybridization, applying a tissue microarray technique. ERBB2 overexpression and ERBB2 amplification were defined according to the recommendations of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) for breast cancer and gastric carcinoma (GC), revealing scores of 2+ and 3+ in 10.2% and 41.8% of UTUCs, respectively. The performance parameters showed obviously higher sensitivity of ERBB2 immunoscoring according to the ASCO/CAP criteria for GC. ERBB2 amplification was detected in 10.5% of UTUCs. ERBB2 overexpression was more likely to be found in high-grade tumors and was associated with tumor progression. Univariable Cox regression analysis revealed a significantly lower progression-free survival (PFS) in cases with ERBB2 immunoscores of 2+ or 3+ according to the ASCO/CAP guidelines for GC. UTUCs with ERBB2 amplification showed a significantly shorter PFS in the multivariable Cox regression analysis. Irrespective of their ERBB2 status, patients with UTUC treated with platin showed a significantly lower PFS than UTUC patients who had not received any platin-based therapy. In addition, UTUC patients with a normal ERBB2 gene status who had not received platin-based therapy showed significantly longer overall survival. The results suggest that ERBB2 is a biomarker for progression in UTUCs and may define a distinct subgroup of UTUCs. As previously shown, ERBB2 amplification is infrequent. However, the small number of patients diagnosed with ERBB2-amplified UTUC might benefit from ERBB2-targeted cancer therapy. In clinical–pathological routine diagnostics, the determination of ERBB2 amplification is an established method in some defined entities and also successful in small samples. Still, the simultaneous use of ERBB2 immunohistochemistry and ERBB2 in situ hybridization would be important in order to record the low rate of amplified UTUC cases as completely as possible

Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011

Background Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients. Methods Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival. Results The number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97–0.97), sex (OR 1.18, 95% CI 1.11–1.25), date of diagnosis (OR 1.05, 95% CI 1.04–1.06), ‘diagnosis during screening’ (OR 3.24, 95% CI 2.50–4.19) and place of residence (OR 1.23, 95% CI 1.16–1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8–83.9%). Conclusions No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008.

Chances and Challenges of Registry-Based Pharmacovigilance in Multiple Sclerosis: Lessons Learnt from the Implementation of the Multicenter REGIMS Registry

The long-term and potential rare side effects of new immunomodulating drugs for the treatment of multiple sclerosis (MS) are often not well known. Spontaneous case report systems of adverse drug effects are a valuable source in pharmacovigilance, but have several limitations. Primary data collections within registries allow a comprehensive analysis of potential side effects, but face several challenges. This article will outline the chances and challenges of registry-based adverse event reporting, using the example of the German immunotherapeutic registry REGIMS. REGIMS is an observational, clinical multicenter registry that aims to assess the incidence, type, and consequences of side effects of MS immunotherapies. Patients treated with an approved MS medication are recruited by their physicians during routine visits in hospitals, outpatient clinics, and MS-specialized practices. REGIMS incorporates an electronic physician-based documentation in each center and a paper-based patient documentation, both at baseline and regular follow-up visits. By the end of 2019, 43 REGIMS centers were actively recruiting patients and performing follow-up documentations. The majority of the first 1000 REGIMS patients were female (69.3%), had relapse-remitting MS (89.8%), and were treated with a second-line therapy. During the implementation of REGIMS, several logistic and procedural challenges had to be overcome, which are outlined in this paper. Pharmacovigilance registries such as REGIMS provide high-quality primary data from a specific patient population in a real-world care setting and enable pharmacovigilance research that cannot be carried out using secondary data. Despite the logistic and procedural challenges in establishing a multicenter pharmacovigilance registry in Germany, the advantages outweigh the drawbacks

Additional file 4: Table S3. of Tumour stage distribution and survival of malignant melanoma in Germany 2002–2011

Relative 5-year survival of malignant melanoma patients diagnosed between 2002 and 2011, overall (UICC 0-IV, X) (N = 60 672) and for patients with invasive tumours (UICC I – IV, X) stratified by age, sex, UICC stage, ‘diagnosis during screening’ and place of residence (N = 49 351) (DOCX 39 kb