Diagnosis of urinary bladder urothelial carcinoma by immunocytology with p53, MCM5, MCM2 and Ki-67 antibodies using cell blocks derived from urine.

OBJECTIVE: Immunocytochemistry has attained a marginal role in urology so far. Combining the morphological and immunophenotypical changes of the urothelial cells retrieved from urine is a logical approach. The study aimed to analyse the diagnostic potential of immunocytological staining in the detection of high-grade and low-grade urothelial carcinoma. METHODS: Freshly voided urine was collected from 152 consecutive individuals, cytology classes were determined and cell blocks produced. A total of 77 patients were diagnosed with urothelial carcinoma and 75 patients had various benign urological conditions. Immunocytochemistry was performed using four antibodies: p53, MCM2, MCM5 and Ki-67. A diagnostic power to detect low grade and high-grade urothelial carcinoma was analysed for each antibody and their combinations with cytology. RESULTS: There were no significant differences between patients with low-grade tumours and control group. Antibodies p53 and Ki-67 slightly improved the sensitivity of urinary cytology while maintaining its specificity. The best negative predictive value was demonstrated in combinations of cytology and MCM5 (88.9%) and cytology, p53 and MCM5 (90.6%). In the diagnosis of high-grade tumours, all antibodies apart from MCM2 yielded better sensitivity and specificity than cytology alone (receiver operating characteristic curves: p53 = 0.853, MCM5 = 0.931, and Ki-67 = 0.895). Combined with cytology, the sensitivities went even higher for the cost of lower specificity. The best diagnostic performance was observed in the combination of MCM5 and Ki-67 (sensitivity = 96.2%; specificity = 80%). CONCLUSIONS: Immunocytochemistry with p53, MCM5 and Ki-67 antibodies can improve the diagnostic power of urinary cytology in the detection and follow-up of urinary bladder urothelial carcinoma.

Clinical and cytopathological factors affecting the cellularity of urinary cell blocks and the implication for diagnosis and follow-up of urinary bladder urothelial carcinoma.

OBJECTIVE: The methodology of cell blocks (CBs) has long been an integrated part of cytology. However, there are very few data on CBs derived from urine. Their main disadvantage is a lack of cellularity, which limits their broader clinical applicability. Factors affecting cellular adequacy in urine remain unclear. We assessed the impact of basic clinical and cytopathological factors on the adequacy of cellularity in urinary CBs. METHODS: Freshly voided urine was collected from 401 consecutive individuals. Of these, 167 patients were diagnosed with urothelial carcinoma. The remaining 234 patients had various benign urological conditions. Papanicolaou classes were determined and CBs produced. Cellular adequacy was assigned to each CB (acellular, hypocellular, moderate cellularity, high cellularity), and moderately and highly cellular CBs were considered as adequate. Several factors were analysed to find any correlation with the adequacy of the cellularity. RESULTS: In univariate analysis, seven factors significantly correlated with the adequacy of the CBs. In the multivariate model, positive sediment (OR = 3.7), female sex (OR = 2.7), positive urinary cytology (OR = 2.6) and positive leucocyturia (OR = 2.1) were independent predictors of adequate cellularity. Positive predictive value and negative predictive value of the model were 65.0% and 77.7%, respectively. CONCLUSIONS: We determined four clinical and cytopathological factors which independently predict adequate cellularity in urinary CBs. Based on these results, several clinical situations have been proposed, in which the highest probability of adequate cellularity in urinary CBs can be achieved.

Diagnostic and prognostic value of placental growth factor serum concentration in clear cell renal cell carcinoma.

BACKGROUND AND AIM: Placental Growth Factor (PlGF) plays a crucial role in angiogenesis and was identified as a potential prognostic biomarker in various types of cancer. Therefore, we evaluated the diagnostic accuracy and prognostic value of PlGF serum concentration in patients with clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: A total of 49 patients subjected to partial or radical nephrectomy for ccRCC [localized without relapse (lccRCC; n=31), localized with later relapse (rccRCC; n=8), primary metastatic cancer (mccRCC; n=10); median of follow-up 4.4 years] were enrolled in a prospective study to assess the significance of PlGF serum concentration. PlGF was measured prior to surgery and 3 months postoperatively. Our control group consisted of 38 healthy subjects. RESULTS: PlGF serum concentration was significantly higher in ccRCC compared to controls (P=0.002). The cut-off value of PlGF concentration for the risk of ccRCC was determined at 12.71 pg/mL (AUC=0.729; P=0.0001). Prior to surgery, among ccRCC subgroups, significantly higher PlGF concentration was detected in mccRCC compared to lccRCC (P=0.002). Postoperatively, we observed a tendency to higher PlGF serum concentration in rccRCC compared to lccRCC subgroup, however without significance (P=0.17). The cut-off value for the risk of relapse was 11.41 pg/mL (AUC=0.792; P=0.0003). In subjects with localized ccRCC with PlGF concentration below 11.41 pg/mL 3-years cancer specific survival was 93% compared to 61% in subject with concentration above the cut-off value (P=0.018). CONCLUSION: Based on our findings, PlGF serum concentration seems to be a useful biomarker in diagnostics and prediction of prognosis in ccRCC.

The Significance of Pregnancy-associated Plasma Protein a Serum Concentration in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: Proteinase pregnancy-associated plasma protein A (PAPP-A) modulates the cell growth and carcinogenesis process. Its role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to evaluate the significance of PAPP-A serum concentration in diagnosis, follow-up and prognosis of ccRCC patients. MATERIALS AND METHODS: In a prospective study including 121 patients who underwent radical or partial nephrectomy for ccRCC [localized ccRCC without relapse (n=80), localized ccRCC with later relapse (n=26), primary metastatic cancer (n=15)] PAPP-A serum concentration was assessed preoperatively and in certain subgroups also postoperatively. RESULTS: PAPP-A serum concentration showed no statistically significant difference between ccRCC and controls and among ccRCC subgroups, respectively. Disease stage and Fuhrman's grade were not shown to affect PAPP-A concentration. The dynamics of postoperative PAPP-A concentrations did not reveal any significance and PAPP-A was not a prognostic factor for cancer related or overall survival. CONCLUSION: PAPP-A serum concentration does not seem to be a useful biomarker in ccRCC.