Prevalence of Molecular Alterations in a Swiss Cohort of 512 Colorectal Carcinoma Patients by Targeted Next-Generation Sequencing Analysis in Routine Diagnostics.

INTRODUCTION: Colorectal carcinoma (CRC) is among the most common carcinomas in women and men. In the advanced stage, patients are treated based on the RAS status. Recent studies indicate that in the future, in addition to KRAS and NRAS, alterations in other genes, such as PIK3CA or TP53, will be considered for therapy. Therefore, it is important to know the mutational landscape of routinely diagnosed CRC. METHOD: We report the molecular profile of 512 Swiss CRC patients analyzed by targeted next-generation sequencing as part of routine diagnostics at our institute. RESULTS: Pathogenic and likely pathogenic variants were found in 462 (90%) CRC patients. Variants were detected in TP53 (54.3%), KRAS (48.2%), PIK3CA (15.6%), BRAF (13.5%), SMAD4 (10.5%), FBXW7 (7.8%), NRAS (3.5%), PTEN (2.7%), ERBB2 (1.6%), AKT1 (1.5%), and CTNNB1 (0.9%). The remaining pathogenic alterations were found in the genes ATM(n= 1), MAP2K1(n= 1), and IDH2(n= 1). DISCUSSION/CONCLUSIONS: Our analysis revealed the prevalence of potential predictive markers in a large cohort of CRC patients obtained during routine diagnostic analysis. Furthermore, our study is the first of this size to uncover the molecular landscape of CRC in Switzerland.

Idiopathic lymphatic mesenteric cyst of the proximal jejunum: A case report of an unusual clinical presentation.

INTRODUCTION: Mesenteric cysts are rare lesions of the abdominal cavity or retroperitoneum. The exact etiopathogenesis is still undefined. Clinical manifestation can vary from asymptomatic patients to symptoms of an acute abdomen, making diagnosis very challenging. CASE PRESENTATION: We present a case of a 47-year-old male with new ongoing polyuria and nocturia as well as episodes of slight abdominal pain. An abdominal ultrasound showed ascites and the computer tomography (CT) scan raised suspicion of an internal hernia. We performed a diagnostic laparoscopy and open resection of a cystic lesion of the small bowel mesentery. The histological examination revealed a lymphatic mesenteric cyst. DISCUSSION: Mesenteric cysts represent rare intra-abdominal tumors that physicians should consider as a differential diagnosis in patients with abdominal pain and an intra-abdominal mass. CONCLUSION: Surgery should be advised to prevent the development of complications and to confirm the histopathological diagnosis.

Toward a Platform for Structured Data Acquisition in Oncology: A Pilot Study on Prostate Cancer Screening.

INTRODUCTION: Physicians spend an ever-rising amount of time to collect relevant information from highly variable medical reports and integrate them into the patient's health condition. OBJECTIVES: We compared synoptic reporting based on data elements to narrative reporting in order to evaluate its capabilities to collect and integrate clinical information. METHODS: We developed a novel system to align medical reporting to data integration requirements and tested it in prostate cancer screening. We compared expenditure of time, data quality, and user satisfaction for data acquisition, integration, and evaluation. RESULTS: In a total of 26 sessions, 2 urologists, 2 radiologists, and 2 pathologists conducted the diagnostic work-up for prostate cancer screening with both narrative reporting and the novel system. The novel system led to a significantly reduced time for collection and integration of patient information (91%, p < 0.001), reporting in radiology (44%, p < 0.001) and pathology (33%, p = 0.154). The system usage showed a high positive effect on evaluated data quality parameters completeness, format, understandability, as well as user satisfaction. CONCLUSION: This study provides evidence that synoptic reporting based on data elements is effectively reducing time for collection and integration of patient information. Further research is needed to assess the system's impact for different patient journeys.

Patterns of stemness-associated markers in the development of castration-resistant prostate cancer.

BACKGROUND: Putative castration-resistant (CR) stem-like cells (CRSC) have been identified based on their ability to initiate and drive prostate cancer (PCa) recurrence following castration in vivo. Yet the relevance of these CRSC in the course of the human disease and particularly for the transition from hormone-naive (HN) to castration-resistance is unclear. In this study, we aimed at deciphering the significance of CRSC markers in PCa progression. METHODS: We constructed a tissue microarray comprising 112 matched HN and CR tissue specimens derived from 55 PCa patients. Expression of eight stemness-associated markers (ALDH1A1, ALDH1A3, ALDH3A1, BMI1, NANOG, NKX3.1, OCT4, SOX2) was assessed by immunohistochemistry and scored as a percentage of positive tumor cells. For each marker, the resulting scores were statistically analyzed and compared to pathological and clinical data associated with the samples. Unsupervised clustering analysis was performed to stratify patients according to the expression of the eight CRSC markers. Publicly-available transcriptional datasets comprising HN and CR PCa samples were interrogated to assess the expression of the factors in silico. RESULTS: Immunohistochemical assessment of paired samples revealed atypical patterns of expression and intra- and intertumor heterogeneity for a subset of CRSC markers. While the expression of particular CRSC markers was dynamic over time in some patients, none of the markers showed significant changes in expression upon the development of castration resistance (CR vs HN). Using unsupervised clustering approaches, we identified phenotypic subtypes based on the expression of specific stem-associated markers. In particular, we found (a) patterns of mutual exclusivity for ALDH1A1 and ALDH1A3 expression, which was also observed at the transcriptomic level in publicly-available PCa datasets, and (b) a phenotypic cluster associated with more aggressive features. Finally, by comparing HN and CR matched samples, we identified phenotypic cluster switches (ie, change of phenotypic cluster between the HN and CR state), that may be associated with clinical and predictive relevance. CONCLUSIONS: Our findings indicate stemness-associated patterns that are associated with the development of castration-resistance. These results pave the way toward a deeper understanding of the relevance of CRSC markers in PCa progression and resistance to androgen-deprivation therapy.

Molecular Profile of Gastrointestinal Stromal Tumors in Sixty-Eight Patients from a Single Swiss Institution.

INTRODUCTION: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. It has distinct molecular features and primarily affects the KIT and PDGFRA genes. OBJECTIVE: We wanted to assess the molecular profile of 68 GIST patients who were sequenced consecutively between 2014 and 2019 at our institute of pathology. METHODS: Our cohort comprised 60 primary and 8 metastatic GIST patients; 43 and 57% of the cases, respectively, were analyzed by Sanger sequencing or next-generation sequencing (NGS). RESULTS: Of the 60 primary GIST patients, 47 (78%) showed a KIT mutation; 2 cases showed a double KIT mutation, and 1 of these was a therapy-naive GIST. Nine (15%) patients harbored a PDGFRA mutation, 2 (3%) had a BRAF mutation, 1 (2%) had a PIK3CA mutation, and 1 (2%) did not show any mutation. One BRAF and the PIK3CA mutation have not been described in GIST before. All metastatic GIST harbored exclusively KIT mutations. CONCLUSION: A retrospective analysis of GIST sequenced at our institute revealed incidences of KIT and PDGFRA mutations comparable to those in other cohorts from Europe. Interestingly, we found 2 previously undescribed mutations in the BRAF and PIK3CA genes as well as 1 treatment-naive case with a double KIT mutation in exon 11.