K. Lindemann-Docter

Proteomic tissue profiling for the improvement of grading of noninvasive papillary urothelial neoplasia.

OBJECTIVES In 2004, a novel grading system for papillary non-invasive bladder cancer was introduced; low grade (LG) and high grade (HG) in lieu of the former G1, G2, G3. This change allowed for increased reproducibility as well as diminished interobserver variability in histopathological grading among individual pathologists. Matrix Assisted Laser Desorption/Ionization Time of Flight Imaging Mass Spectrometry (MALDI TOF IMS) was evaluated as an automatic and objective tool to assist grading of urothelial neoplasms and to facilitate accuracy. DESIGN AND METHODS To separate G1 (LG, n=27) and G3 (HG, n=21) papillary tumors MALDI TOF IMS was performed using an appropriate algorithm. Thereafter, the automatic assignment of a separate G2 (n=31) group was completed. RESULTS G1 (LG) and G3 (HG) tumors were separated with an overall cross validation of 97.18%. G2 tumors indicated a true positive rate of 78.3% for LG and 87.5% for HG, respectively. CONCLUSIONS MALDI TOF IMS is a powerful support tool to ascertain pathological diagnosis/grading.

Current knowledge in molecular pathology of urothelial cancer

Results of molecular pathology have supported changes in the 2004 WHO classification of urothelial cancer. Since then new molecular data such as the distribution pattern of the fibroblast growth factor receptor 3 (FGFR3) has further supported the principle of low and high grade entities of urothelial carcinoma. Animal experiments with knockout mice and conditional knockout systems reveal important parallels to humans and results emphasize the cellular context as a trigger for malignancy. One special feature of the urothelium is its high protection of the urothelial cells by members of the retinoblastoma gene family, efficiently inhibiting invasion even in the presence of p53 mutations. In search of the tumor stem cell phenotype the basal cell phenotype is the focus of attention providing a high clonogenic potential. At the same time detailed analysis of the distribution of mutations in the mitochondrial genome within the urothelium will help to gain insight into the spreading of normal cell or tumor cell clones. The overall data in urological oncology provide evidence that diagnostic and prognostic tools for urothelial cancer can only be reached with multiparametric approaches.

Stand des Wissens zur molekularen Pathologie des Urothelkarzinoms

Results of molecular pathology have supported changes in the 2004 WHO classification of urothelial cancer. Since then new molecular data such as the distribution pattern of the fibroblast growth factor receptor 3 (FGFR3) has further supported the principle of low and high grade entities of urothelial carcinoma. Animal experiments with knockout mice and conditional knockout systems reveal important parallels to humans and results emphasize the cellular context as a trigger for malignancy. One special feature of the urothelium is its high protection of the urothelial cells by members of the retinoblastoma gene family, efficiently inhibiting invasion even in the presence of p53 mutations. In search of the tumor stem cell phenotype the basal cell phenotype is the focus of attention providing a high clonogenic potential. At the same time detailed analysis of the distribution of mutations in the mitochondrial genome within the urothelium will help to gain insight into the spreading of normal cell or tumor cell clones. The overall data in urological oncology provide evidence that diagnostic and prognostic tools for urothelial cancer can only be reached with multiparametric approaches.

Nicht-invasive und invasive Urothelneoplasien

The current 2004 WHO classification of bladder tumors categorizes non-invasive and invasive urothelial neoplasms into prognostically relevant groups according to the histopathological cell morphology and underlying genetic changes. Although many parts of the classification have not been changed dramatically, even small changes have caused uncertainty and scepticism among urologists and pathologists in recent years. The following review article is structured into various challenges for urologists and pathologists and provides an overview of rare but clinically relevant subgroups and diagnostics, interpretation of diagnoses and pathological findings with respect to consequences for the daily clinical routine (extended diagnosis, therapy and prognosis).

Uringebundene Marker mit besonderer Berücksichtigung der Fluoreszenz-in-situ-Hybridisierung (FISH)

ZusammenfassungFür den Patienten ist eine nichtinvasive oder minimal-invasive Diagnostik von Erkrankungen attraktiv. Für deren Einsatz muss jedoch die Validität der Untersuchung kontrolliert werden, um wirklich eine Verbesserung in der Patientenversorgung zu erreichen. Die Urinzytologie zur Detektion von Tumorzellen kann als valide Methode für die Detektion von Tumorzellen angesehen werden, wenn nach High-grade-Tumorzellen gesucht wird. High-grade-Tumorzellen erachten wir als klinisch relevanten Befund der Untersuchung von Urinproben. Die Fluoreszenz-in-situ-Hybridisierung (FISH) von Interphasekernen an zentromerischen und genspezifischen Loci ist für die Detektion des Urothelkarzinoms optimiert worden und erhöht die Sensitivität des Tumornachweises. Durch die FISH entsteht die Möglichkeit, die Häufigkeit der Zystoskopien in der Nachsorge von Tumorpatienten individueller anzupassen.AbstractPatient care with noninvasive or minimally invasive methods is appealing for the patient. It has to be assessed in terms of validity to guarantee improvement of patient care. Urine cytology for the detection of tumour cells can be considered a valid method since its specificity and sensitivity is high when high-grade tumour cells are sought. High-grade tumour cells are considered the clinically most relevant finding in urine specimens. Fluorescent in situ hybridization of interphase nuclei on centromeric and gene loci has been optimized for urothelial carcinoma and increases the sensitivity of tumour findings. It also gives a valid chance to adapt the number of cystoscopies in the follow-up of bladder cancer patients more individually.

Urine markers with special regard to fluorescent in situ hybridization (FISH)

ZusammenfassungFür den Patienten ist eine nichtinvasive oder minimal-invasive Diagnostik von Erkrankungen attraktiv. Für deren Einsatz muss jedoch die Validität der Untersuchung kontrolliert werden, um wirklich eine Verbesserung in der Patientenversorgung zu erreichen. Die Urinzytologie zur Detektion von Tumorzellen kann als valide Methode für die Detektion von Tumorzellen angesehen werden, wenn nach High-grade-Tumorzellen gesucht wird. High-grade-Tumorzellen erachten wir als klinisch relevanten Befund der Untersuchung von Urinproben. Die Fluoreszenz-in-situ-Hybridisierung (FISH) von Interphasekernen an zentromerischen und genspezifischen Loci ist für die Detektion des Urothelkarzinoms optimiert worden und erhöht die Sensitivität des Tumornachweises. Durch die FISH entsteht die Möglichkeit, die Häufigkeit der Zystoskopien in der Nachsorge von Tumorpatienten individueller anzupassen.AbstractPatient care with noninvasive or minimally invasive methods is appealing for the patient. It has to be assessed in terms of validity to guarantee improvement of patient care. Urine cytology for the detection of tumour cells can be considered a valid method since its specificity and sensitivity is high when high-grade tumour cells are sought. High-grade tumour cells are considered the clinically most relevant finding in urine specimens. Fluorescent in situ hybridization of interphase nuclei on centromeric and gene loci has been optimized for urothelial carcinoma and increases the sensitivity of tumour findings. It also gives a valid chance to adapt the number of cystoscopies in the follow-up of bladder cancer patients more individually.

Uringebundene Marker mit besonderer Berücksichtigung der Fluoreszenz-in-situ-Hybridisierung (FISH)@@@Urine markers with special regard to fluorescent in situ hybridization (FISH)

ZusammenfassungFür den Patienten ist eine nichtinvasive oder minimal-invasive Diagnostik von Erkrankungen attraktiv. Für deren Einsatz muss jedoch die Validität der Untersuchung kontrolliert werden, um wirklich eine Verbesserung in der Patientenversorgung zu erreichen. Die Urinzytologie zur Detektion von Tumorzellen kann als valide Methode für die Detektion von Tumorzellen angesehen werden, wenn nach High-grade-Tumorzellen gesucht wird. High-grade-Tumorzellen erachten wir als klinisch relevanten Befund der Untersuchung von Urinproben. Die Fluoreszenz-in-situ-Hybridisierung (FISH) von Interphasekernen an zentromerischen und genspezifischen Loci ist für die Detektion des Urothelkarzinoms optimiert worden und erhöht die Sensitivität des Tumornachweises. Durch die FISH entsteht die Möglichkeit, die Häufigkeit der Zystoskopien in der Nachsorge von Tumorpatienten individueller anzupassen.AbstractPatient care with noninvasive or minimally invasive methods is appealing for the patient. It has to be assessed in terms of validity to guarantee improvement of patient care. Urine cytology for the detection of tumour cells can be considered a valid method since its specificity and sensitivity is high when high-grade tumour cells are sought. High-grade tumour cells are considered the clinically most relevant finding in urine specimens. Fluorescent in situ hybridization of interphase nuclei on centromeric and gene loci has been optimized for urothelial carcinoma and increases the sensitivity of tumour findings. It also gives a valid chance to adapt the number of cystoscopies in the follow-up of bladder cancer patients more individually.