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Nuclear Theranostics in Asia: In vivo Companion Diagnostics

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Serum Hepcidin and GDF-15 levels as prognostic markers in urothelial carcinoma of the upper urinary tract and renal cell carcinoma

Abstract

Background

Cancer is a life-threatening disease that causes every fourth death. It is often hard to determine the time point of progression. Therefore, biomarkers for cancer entities that indicate disease progression or aggressiveness and thereby guide therapeutic decisions are required. Unfortunately, reliable biomarkers are rare. In this study, the potential of serum hepcidin and serum GDF-15 as biomarkers that correlate with patient's survival in the two entities upper urinary tract urothelial carcinomas (UUTUC) and renal cell carcinoma (RCC) were analyzed.

Methods

In this retrospective study n = 38 patients suffering from UUTUC, n = 94 patients suffering from RCC and n = 21 patients without infections or cancer, all hospitalized at the University Hospital Muenster, were included. Serum samples of patients were retrospectively analyzed. Serum hepcidin and GDF-15 levels were measured and correlated to aggressiveness and progression of the disease as well as patient's outcome.

Results

For both entities, UUTUC and RCC, serum hepcidin levels as well as serum GDF-15 levels were increased compared to sera of controls. High serum hepcidin and GDF-15 levels were associated with metastases and cancer relapse. Also, in both entities, the overall survival was decreased in patients with increased serum hepcidin and GDF-15 levels. Hence, high serum hepcidin and GDF-15 levels correlated with patient's outcome.

Conclusion

To conclude, the data of this study show a correlation of high serum hepcidin and GDF-15 levels with aggressiveness and progression of the disease and demonstrate potential prognostic properties of serum hepcidin and GDF-15 levels. The data support the further assessment of serum hepcidin and GDF-15 as prognostic markers in RCC and UUTUC.

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Risk‐stratified surveillance in dermatofibrosarcoma protuberans: Less is more

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Nonmosaic somatic HIF2A mutations associated with late onset polycythemia‐paraganglioma syndrome: Newly recognized subclass of polycythemia‐paraganglioma syndrome

Background

Somatic mutations in hypoxia‐inducible factor 2α (HIF2A) are associated with polycythemia‐paraganglioma syndrome. Specifically, the classic presentation of female patients with recurrent paragangliomas (PGLs), polycythemia (at birth or in early childhood), and duodenal somatostatinomas has been described. Studies have demonstrated that somatic HIF2A mutations occur as postzygotic events and some to be associated with somatic mosaicism affecting hematopoietic and other tissue precursors. This phenomenon could explain the development of early onset of polycythemia in the absence of erythropoietin‐secreting tumors.

Methods

Correlation analysis was performed between mosaicism of HIF2A mutant patients and clinical presentations.

Results

Somatic HIF2A mutations (p.A530V, p.P531S, and p.D539N) were identified in DNA extracted from PGLs of 3 patients. No somatic mosaicism was detected through deep sequencing of blood genomic DNA. Compared with classic syndrome, both polycythemia and PGL in all 3 patients developed at an advanced age with polycythemia at age 30, 30, and 17 years and PGLs at age 34, 30, and 55 years, respectively. Somatostatinomas were not detected, and 2 patients had ophthalmic findings. The biochemical phenotype in all 3 patients was noradrenergic with ¹⁸F‐fluorodopa PET/CT as the most sensitive imaging modality. All patients demonstrated multiplicity, and none developed metastatic disease.

Conclusion

These findings suggest that newer techniques need to be developed to detect somatic mosaicism in patients with this syndrome. Absence of HIF2A mosaicism in patients with somatic HIF2A mutations supports association with late onset of the disease, milder clinical phenotype, and an improved prognosis compared with patients who have HIF2A mosaicism.

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Outcome after surgical treatment of dermatofibrosarcoma protuberans (DFSP): Is clinical follow‐up always indicated?

Background

Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma for which clinical examination up to 10 years is recommended. The objective of this study was to identify prognostic factors for recurrences and metastases that can be used to evaluate the validity of follow‐up schedules after treatment for DFSP.

Methods

Patients with DFSP who received treatment between 1991 and 2016 at 3 tertiary centers were included. Cox regression analyses were conducted to identify variables associated with the primary endpoints.

Results

In total 357 patients were included, with a median age of 38 years (age range, 2‐87 years) and a median follow‐up of 60 months (interquartile range, 24‐115 months). Eighty‐one patients developed recurrent disease (22.7%), and the median time to recurrence was 55.5 months (interquartile range, 20‐90 months). Of these, 50 tumors (61.7%) were identified by patient self‐examination, whereas 3 recurrences (3.7%) were identified at clinical surveillance. For the remaining 28 tumors, no information was available on how the recurrences were identified (34.6%). Fibrosarcomatous change (hazard ratio, 21.865; P < .001), and positive resection margins (hazard ratio, 14.645; P < .001), were independent prognostic factors for recurrence. Metastases occurred in 4 patients (1.1%). All tumors were identified by imaging after patients presented with symptomatic metastases. Fibrosarcomatous change (P < .001) and tumor size >5 cm (P = .014) were associated with the development of metastases.

Conclusions

Disease recurrence after resection of DFSP remains a significant issue, whereas metastases are uncommon. The majority of recurrences are identified by patient self‐examination. Consideration should be given to individualized follow‐up schedules based on risk factors for recurrences and metastases.

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Clonal haematopoiesis – a source of biological noise in cell-free DNA analyses

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