Biomedical subjects

P Kapralos

Publications and source records attributed to P Kapralos.

7 recordsLinked to original sources

PubMed2001

Prognostic implications of aberrations in p16/pRb pathway in urothelial bladder carcinomas: a multivariate analysis including p53 expression and proliferation markers.

OBJECTIVE: To assess the prognostic value of the expression of two negative regulators of the cell cycle, namely CDKN2/INK4a gene product (p16) and retinoblastoma gene product (pRb), in urinary bladder cancer in relation to clinicopathological parameters, proliferative fraction and p53 protein accumulation. METHODS: Paraffin sections from 139 patients with urothelial carcinomas were stained immunohistochemically with antibodies to p16 (F12), pRb (PMG3-245), p53 (DO1), PCNA (PC10) and Ki-67 (MIB-1). RESULTS: Diminished p16 and pRb expression occurred in 29 and 74% of cases, respectively, being associated with advanced stage but not with histological grade, papillary status or proliferation rate. In most cases (53%) with some fault in the p16/pRb pathway, only one gene was affected. A double-negative p16/pRb phenotype was comparatively uncommon (25%) and was usually seen in T3-T4 tumours. In survival analysis (either univariate or multivariate) aberrant p16 expression was an adverse prognostic parameter only in T3-T4 tumours. In contrast, the abnormal p16/pRb and p53/p16 phenotypes were linked to a diminished overall and disease-free survival (univariate analysis); p53/p16 abnormal expression was also found to be an independent predictor of reduced survival in muscle-invasive tumours, while proliferation markers were the only parameters with independent significance in superficial (Ta-T1) tumours. CONCLUSION: Our results suggest that lack of p16 immunoexpression, when combined with p53 accumulation, plays an important role in determining the clinical outcome in muscle-invasive urothelial carcinomas.

Adult↗

PubMed2000

Apoptosis in bladder carcinomas detected with monoclonal antibody to single-stranded DNA: relation to cell cycle regulators and survival.

OBJECTIVES: To investigate the incidence of baseline apoptosis in relation to p27(Kip1), p53, and p21(Cip1) expression, proliferation status, standard clinicopathologic parameters, and patient outcome. Cell cycle regulators and apoptotic cell death have been implicated in tumor aggressiveness in many human malignancies. Their interaction, however, in the prognosis of patients with transitional cell carcinoma (TCC) of the urinary bladder has not yet received intense scrutiny. METHODS: Apoptotic fractions were quantified immunohistochemically by means of a novel monoclonal antibody recognizing single-stranded DNA regions in apoptotic nuclei in 103 paraffin-embedded primary TCC specimens. Proliferative activity was expressed as the percentage of Ki-67 positive cells (Ki-67 index). Tissue specimens were also stained for p27(Kip1), p53, and p21(Cip1) proteins. Patients were followed up until death (n = 30) or for an average of 40 months (median 36). RESULTS: The apoptotic index increased with grade, T stage, nonpapillary status, proliferative activity, and p53 expression and was inversely related to p27(Kip1) and independently to p21(Cip1) expression. A negative correlation was found between p27(Kip1) expression and proliferation. The increased apoptotic index had an adverse impact on overall and disease-free survival (univariate analysis) and, along with T stage, was an independent predictor in muscle-invasive TCC. CONCLUSIONS: An increased apoptotic rate, increased proliferative activity, and decreased p21(Cip1) expression are independently interrelated in TCC. More importantly, the assessment of apoptotic potential appears to be more informative than standard prognosticators in predicting overall survival in patients with muscle-invasive TCC.

Adult↗

PubMed2000

Cell cycle regulators in bladder cancer: a multivariate survival study with emphasis on p27Kip1.

Cyclin-dependent kinase inhibitors (CKIs) prevent cyclin-dependent kinases from phosphorylating critical substrates such as retinoblastoma gene protein (pRb), hence blocking the cascade of events leading to cell proliferation. Currently, the list of CKIs includes p21WAF1/Cip1, p27Kip1, p57Kip2 (the Cip/Kip family), p15/ INK4b, p16/INK4a, p18/INK4c, and p19/INK4d (the INK4 family). Among them, p27 plays a crucial role linking extracellular growth-regulatory signals to progression to or exit from the cell cycle. Unlike p53, p16, and Rb, mutations in Kip1 and WAF1 genes are distinctly rare in bladder cancer. We analyzed immunohistochemically the expression of p27 and other interacting G1 proteins (ie, p21, p16, pRb, p53) in 120 consecutive cases of transitional cell carcinomas (TCCs) and related it to proliferation rate, clinicopathologic parameters, and survival. p27 levels were significantly higher in low-grade (P = .001), superficial (Ta-T1) (P = .001), papillary (P < .001), and slowly proliferating TCCs (rs = -0.235, P = .05). p27 also positively correlated with p16 expression (rs = 0.212, P = .05). In univariate analysis, decreased p27 expression was associated with poor overall (P = .0109) and postrelapse (P = .0344) survival, especially if combined to increased Ki-67 expression (P = .0004 and P = .036, respectively). Furthermore, in multivariate analysis, Ki-67/p27 status had the strongest bearing on the overall survival of muscle-invasive TCCs (P = .0019). Our results indicate that low p27 expression is more common in poorly differentiated muscle-invasive TCCs and is a major player in cell cycle control in these neoplasms. More importantly, the combined Ki-67/p27 expression provides prognostic information beyond that provided by conventional parameters or other cell cycle-related proteins, concerning overall survival in muscle-invasive TCCs.

Adult↗

PubMed2000

WAF1/p21 protein expression is an independent prognostic indicator in superficial and invasive bladder cancer.

The inhibitor of cyclin-dependent kinases WAF1 gene product p21 is able to arrest mammalian cell cycle by mediating p53 and other factors. The prognostic value and interrelationships between p21 expression and various parameters in bladder cancer have not been fully elucidated. We retrospectively investigated the immunohistochemical expression of p21 protein in consecutive paraffin sections from 131 transitional cell carcinomas (TCCs) and related it to p53 protein expression, clinicopathologic parameters, proliferative fraction, and survival. Positivity was displayed in 45% of cases, among which one fourth was accompanied by p53 accumulation. p21 expression was statistically related to advanced T category. No association was shown between p21 and p53 or proliferation rate. Low grade invasive TCCs tended to be more often p21 positive than high grade invasive TCCs. Most superficial tumors displayed neither p21 nor p53 expression, whereas the combined phenotypes p53/p21+ and p53+/p21- predominated among invasive tumors. P21 labeling index emerged by multivariate analysis as the single independent indicator of shortened overall (P = 0.0294) and disease-free (P = 0.0414) survival in superficial TCCs. Conversely, in invasive tumors, loss of p21 expression was a predictor of shortened disease-free survival (P = 0.0234) and was associated with poor outcome when accompanied by p53 accumulation (P = 0.0033). In conclusion, our results indicate that p21 activation occurs early in tumorigenesis, appears associated with invasiveness, and is capable of cell cycle control in TCCs mostly through p53-dependent pathways. Finally, p21 expression, alone or in combination with p53 and irrespective of other clinicopathologic parameters, plays distinct roles in determining clinical outcome in superficial and invasive tumors, suggesting that urothelial bladder cancer represents two different diseases.

Adult↗

PubMed1997

The role of p53, MDM2 and c-erb B-2 oncoproteins, epidermal growth factor receptor and proliferation markers in the prognosis of urinary bladder cancer.

The immunohistological expression of p53 and MDM2 oncoproteins was examined in paraffin embedded tissue from 106 patients with transitional cell carcinoma of the urinary bladder and was related to various clinicopathological features, the expression of proliferation associated markers (proliferating cell nuclear antigen - PCNA - and Ki-67), c-erb B-2 oncoprotein and epidermal growth factor receptor (EGFR), as well as to survival. MDM2 immunoreactivity was seen in 38% of our cases, and in 14% was accompanied by p53 positive immunohistochemistry. The rate of p53 positivity was associated with grade, stage and papillary status, whereas MDM2 immunopositivity increased with grade and stage (Ta VS T1), and MDM2 labeling index (LI) with stage. MDM2 expression was related to p53 expression and less strongly to proliferation rate (Ki-67 LI). The simultaneous p53 and MDM2 expression was more frequently observed in higher grade and stage tumours. C-erb B-2, EGFR and proliferation marker expression increased with grade, stage and non-papillary configuration. In univariate analysis high grade, solid growth pattern, advanced T-category, cystectomy, EGFR and Ki-67 expression were linked to shorter overall survival but only Ki-67 LI, along with T-category and type of therapy, had independent prognostic value. C-erb B-2 expression and stage were the two independent predictors of disease-free survival and Ki-67 LI and EGFR LI the independent predictors of post-relapse survival. For patients with superficial tumors PCNA LI emerged as the single independent determinator of survival. p53 and MDM2 expression did not appear to have any significant impact on survival, although the simultaneous expression of p53 and MDM2 turned out to be a highly significant parameter of shortened overall survival in univariate analysis.

Adult↗

PubMed1991

Histological changes of the bladder mucosa following the administration of BCG adriamycin and RO 10-9359.

Three groups of Wistar rats have been treated with intravesical Adriamycin and BCG and oral retinoids. The main effect on the bladder seen on histological sections was mononuclear infiltration in the Adriamycin group, polymorphonuclear infiltration in the BCG group and minimal mononuclear and polymorphous infiltration in the retinoid group. The results are discussed in relation to the existing theories on the protective action of these agents against bladder tumour recurrences.

Administration, Intravesical↗

PubMed1979

Unilateral emphysematous pyelonephritis.

A case of unilateral emphysematous pyelonephritis is presented in a patient with uncontrolled diabetes mellitus. The diagnosis was established from the presence of gas in the renal parenchyma, the pelvicalyceal system and the ureter. The patient was treated with a prolonged course of antibiotics and the function of the left kidney returned to normal.

Adult↗