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Epithelial differentiation antigens have been correlated with morphologic differentiation of neoplastic urothelium. Moreover, epidermal growth factor, which is a polypeptide regulating growth and differentiation of normal and neoplastic cells, is found in high concentrations in the urine while its receptors (EGFR) have been identified in bladder tumors. The aim of this study was to investigate the immunohistochemical expression of cytokeratin, epithelial membrane antigen (EMA), CEA and EGFR in transitional cell bladder carcinomas (TCC) and to define any correlation of their expression with tumor grade, stage and patient survival. Twenty-four biopsy specimens obtained from patients with TCC were studied retrospectively. There were 23 men and 1 woman with a mean follow-up of 64 months. Eight biopsy specimens, which represented tumor recurrences of 4 patients, were also included in our material. The immunohistochemical avidin-biotin complex method was performed on paraffin sections for the detection of cytokeratin and EGFR with monoclonal antibodies as well as CEA with a polyclonal antibody. Cytokeratin was detected in 83.5% of the TCC, EMA in 62% and CEA in 70%. The expression of the epithelial differentiation antigens in TCCs was heterogenous, showing an increased incidence in high-grade and high-stage TCC. The CEA expression in TCC demonstrated a statistically significant correlation with patient survival (p < 0.02). EGFR was detected in 50% of the TCC. Although not statistically significant, a trend was found for a higher percentage of EGFR detection in high-grade TCC. EGFR expression was significantly associated with tumor stage and patient survival (p < 0.01 and p < 0.04, respectively). In conclusion, EGFR and CEA expression is a property of biologically aggressive malignant urothelium. Studies on larger series are to be performed to define if these markers are prognostic indicators in bladder cancer patients.

Objectives. p53 tumor suppressor gene is considered to play a significant role in carcinogenesis. Mutations in the p53 are the most frequent genetic abnormalities encountered in human malignancies. Our aim was to investigate the expression of p53 oncoprotein in superficial and invasive transitional cell bladder cancer (TCC) as well as its correlation with established prognostic factors, such as histologic grade, tumor stage, DNA content, and survival. Methods. Forty-five patients with superficial TCC (Ta-T1) and 42 with invasive TCC (T2-T4) were included in our study. Material from transurethral biopsy was examined using an immunohistochemical method and the monoclonal antibody Pab 1801. Results. p53 tumor suppressor protein was overexpressed in 48.3% of TCC cases and more frequently in invasive than superficial TCCs (P = 0.03) and undetectable in the tumor adjacent to normal tissue. p53 positivity was related to the degree of differentiation and with the stage of the disease of invasive TCCs (P = 0.03 and P = 0.004, respectively), whereas no statistical significance was documented for superficial TCCs. Moreover, p53 overexpression demonstrated a statistical significance with DNA ploidy in superficial Ta-T1 tumors (P = 0.04) and was suggestive in invasive T2-T4 tumors (P = 0.08). There was no correlation of recurrence related to p53-positive superficial tumors (P = 0.29). Patients with p53-positive invasive TCCs showed statistically significant worse survival (P = 0.007), but in multivariate analysis, p53 positivity is not independently related to poor overall survival (P = 0.30). When we combined ploidy and p53 status, we realized that the subset of patients with aneuploidy and p53 positivity had the worst prognosis (P = 0.008). Conclusions. The results suggest the involvement of p53 protein as a ]ate event in bladder carcinogenesis. p53 does not seem to be a prognostic marker for recurrences of superficial tumors and is not independently related to survival. The aneuploidy of tumors correlates with the p53 positivity in bladder cancer. The combined expression of aneuploidy and p53 positivity in invasive tumors has strong association with the survival of patients.

Specimens from 75 cases of prostatic adenocarcinoma of different M.D. Anderson degrees of malignancy were stained immunohistochemically for neuron-specific enolase (NSE), prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP). None of these tumors presented on hematoxylin-eosin sections any features suggesting neuroendocrine differentiation; nevertheless, 18.7% of the tumors were at least focally NSE positive, Because of the synchronous antigenic expression of the NSE-positive cells to PSA and PAP, the authors suggest that prostatic exocrine and neuroendocrine cells derive from a common precursor stem cell. The possibility of a more aggressive biological behavior of these tumors in comparison to the conventional carcinomas is discussed. The probable clinical necessity for a combined therapeutic approach is also investigated.

The PBM package was developed to create, display and conveniently manipulate protein and small molecule structures on IBM-compatible microcomputers. It consists of four modules: CREATE, SPHERE, RIBBON and CONVERT. CREATE includes commands to create or alter ('mutate') the primary and subsequently the tertiary structure of a given peptide or protein by defining φ and ψ angles of residues at will, options to add, delete or alter atoms in a structure, utilities to choose easily between the most common rotamers of amino acid residue sidechains and options to analyse in various ways a protein conformation. SPHERE provides for an interactive manipulation of structures containing up to 2700 atoms which can belong up to six different molecules. All manipulations can be made with the use of an ordinary mouse, by choosing from a variety of pull-down menus. Three types of models can be implemented to display molecules on the computer screen or the plotter: skeletal, solid space-filling and wireframe space-filling models. RIBBON creates ribbon models of proteins and allows for a limited variety of interactive manipulations. CONVERT is a file converter, which is capable of converting files of atom coordinates of literally any format to Brookhaven Data Bank format files. The package produces very good results for protein molecules of reasonable sizes, both in terms of graphics quality and speed of operations, on an 80486 IBM PC-compatible machine equipped with a 1 MByte VGA display card and a colour VGA manitor, which is a recommended configuration. © 1995 Oxford University Press.

Thirty-six transvesical or transurethral prostatectomy cases were selected from the histopathology files of the Laiko General Hospital. Among the 36 cases, there were 10 with benign prostatic hyperplasia (8 patients having distinct areas of adenosis) and 26 cases of prostatic adenocarcinoma (6 grade I, 13 grades II and III and 7 grade IV carcinomas). From each case, silver-binding nucleolar organizer regions (AgNORs) have been counted in sections of routinely processed paraffin-embedded tissue blocks. The mean AgNOR count per case was calculated. For the cases of prostatic hyperplasia, the mean AgNOR count was found to be 2.95 +/- 0.42, for adenosis 3.45 +/- 0.56, for grade I adenocarcinoma 4.97 +/- 0.74, for grades II and III 7.31 +/- 0.81 and for grade IV adenocarcinomas 11.41 +/- 1.68. This difference in the mean AgNOR count was found to be of statistical significance (p < 0.001) between adenosis and grade I adenocarcinomas and between grade II and III and grade IV adenocarcinomas. It appears that AgNOR counting may prove to be of benefit in differentiating between some benign and malignant prostatic lesions and that it might provide information concerning the biological behavior of prostatic adenocarcinomas.