Gabriel Bromiński

To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.

(Cell 179, 964–983.e1–e31; October 31, 2019) In the originally published version of this article, Daniel Geiszler's last name was misspelled. This error has now been corrected in the article online. Integrated Proteogenomic Characterization of Clear Cell Renal Cell CarcinomaClark et al.CellOctober 31, 2019In BriefComprehensive proteogenomic characterization in 103 treatment-naive clear cell renal cell carcinoma patient samples highlights tumor-specific alterations at the proteomic level that are unrevealed by transcriptomic profiling and proposes a revised subtyping scheme based on integrated omics analysis. Full-Text PDF Open Access

Introduction: Klotho has been recently described as a carcinogenesis suppressor. Large cell neuroendocrine lung carcinoma (LCNEC) is a rare, highly malignant neoplasm. In the light of increasing incidence of neuroendocrine tumours, biomarkers predicting survival are needed. We consider that Klotho might be one. Material and methods: We analysed records of all patients diagnosed with LCNEC, atypical carcinoid and typical carcinoid operated on in our institution between 2007 and 2015. Initially, we found 134 cases. Forty-six specimens were unattainable and thus excluded from research. All patients diagnosed with LCNEC according to the WHO classification were included in the study. Immunohistochemical staining for Klotho was performed. We retrospectively reviewed patient charts and analysed multiple variables. Results: Positive staining for Klotho was present in 36 tissue specimens, while 12 patients were Klotho-negative. Survival length was significantly higher in Klotho-positive cases (p = 0.024), while advanced nodal status (N1 and N2) represented a marker of poor outcome (p = 0.011). In multivariate analysis, both Klotho presence (p = 0.015; HR = 0.37; 95% CI: 0.17-0.86) and nodal involvement (p = 0.007; HR = 3.04; 95% CI: 1.37-6.82) were independent prognostic factors. Tumour vessel invasion and visceral pleura infiltration were not associated with worse treatment results. Klotho presence predicted a favourable prognosis in these groups (p = 0.018; p = 0.007). Conclusions: Our results suggest that Klotho might be a positive factor for predicting survival in LCNEC and nodal involvement a negative one. Thus, these two markers may assist in the selection of subjects with unfavourable prognosis and to personalise therapy regimens.

OBJECTIVES: The aim of this study was to investigate the fluorine-18-fluorodeoxyglucose (F-FDG) uptake on integrated PET [PET/computed tomography (CT)] images and its correlation with nestin expression in a series of neuroendocrine lung tumours. As the incidence of neuroendocrine lung tumours is rising, tools predicting diagnosis, outcome and assisting in the selection of treatment regimens are needed. PATIENTS AND METHODS: We reviewed records of patients diagnosed with large cell neuroendocrine lung carcinoma, atypical carcinoid and typical carcinoid who were operated upon in our institution. Into the study, we included those who underwent F-FDG PET/CT before the operation. Immunohistochemical staining for nestin was performed. We retrospectively reviewed patient charts and analyzed multiple variables. RESULTS: Maximal standardized uptake value (SUVmax) was significantly higher in poorly differentiated than in well-differentiated tumours (P<0.001). The estimated SUVmax cut-off value, which distinguishes large cell neuroendocrine lung carcinoma from carcinoid with the highest sensitivity and specificity (88.6%; 85%), was 6.3. Positivity of the tumour on F-FDG PET/CT was associated with shorter survival of the patient (P=0.0057). Multivariate analysis showed that nodal involvement and SUVmax were predictors of adverse outcome. Nestin expression did not correlate with lymph node metastases (P=0.97), SUVmax (P=0.9), maximal size of the lesion (P=0.49) or Ki-67 (P=0.93). Nestin expression did not influence survival on multivariate analysis. CONCLUSION: The study revealed a comparable expression of nestin in tumours with different activity of glucose metabolism measured by F-FDG uptake at PET/CT. It did not show any significant influence of nestin expression on survival. The study confirmed that F-FDG PET/CT is useful in the preoperative evaluation of patients with pulmonary neuroendocrine tumours.