Katsunori Uchida

Immunocytochemical Demonstration of S Phase Cells by Antlbromobeoxyuribine Monoclonal Antibody in Human Prostate Adenocarcinoma

Using a monoclonal antibody to bromodeoxyuridine and immunohistochemistry, we measured the incorporation of this thymidine analogue into the deoxyribonucleic acid of human prostate adenocarcinoma cells exposed in situ. Fifteen patients with prostate cancer were given an intravenous infusion of 500 mg. bromodeoxyuridine at needle biopsy to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70 per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method using anti-bromodeoxyuridine monoclonal antibody as the first antibody. The results showed that this method demonstrated bromodeoxyuridine-labeled nuclei satisfactorily in tissue section. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. Grade 3 tumors averaged 4.37 +/- 0.48 per cent labeling versus 2.41 +/- 0.49 per cent in grade 2 tumors, and grade 1 tumor in the series had an S phase fraction of 1.36 +/- 0.39 per cent. The average S phase fractions for single gland, cribriform, fused and medullary were 1.16, 2.30, 3.74 and 4.95 per cent, respectively. The results obtained with S phase fraction measured with bromodeoxyuridine labeling proved to be comparable to the results of histological grade and growth pattern. Thus, the higher S phase fraction may indicate biological malignancy. Moreover, the degree of heterogeneity concerning S phase fraction distribution within prostate cancer tissue could be compared to the morphological appearance. Our preliminary results suggest that the measurement of bromodeoxyuridine labeling index in prostate cancer may prove to be a new objective and quantitative assay of biological potential of individual tumor.

S Phase Fraction of Human Bladder Tumor Measured in Situ with Bromodeoxyuridine Labeling

A total of 18 patients with transitional cell bladder cancer was given a 0.5-hour intravenous infusion of bromodeoxyuridine at the time of endoscopic biopsy or transurethral resection to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70 per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method with anti-bromodeoxyuridine monoclonal antibody as the first antibody. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. All grade 1 tumors had an S phase fraction of lower than 10 per cent. The average S phase fractions for noninvasive (11 cases) and invasive (7) tumors were 9.8 and 20.0 per cent, respectively. Two distant metastatic bladder tumors showed an average S phase fraction of 25.3 and 30.0 per cent. Thus, transitional cell bladder cancers with an S phase fraction of greater than 10 per cent appears to grow faster and be more invasive more often than those with an S phase fraction of less than 10 per cent. The higher S phase fraction may indicate greater biological malignancy. Our preliminary results suggest that measurement of the bromodeoxyuridine labeling index in bladder tumors may be a new objective and quantitative assay of biological potential of individual tumors.

Immunohistochemical Detection of Proliferating Cell Nuclear Antigen (Pcna)/Cyclin in Human Prostate Adenocarcinoma

Tissue specimens from 12 patients with adenocarcinoma of the prostate and 7 patients with benign prostate hypertrophy were stained by an indirect immunoperoxidase method using antiproliferating cell nuclear antigen (PCNA) monoclonal antibody. The PCNA labeling index was determined by counting the number of PCNA-labeled cells in the tissue sections. Average PCNA labeling index of the benign prostate hypertrophy was 1.2 +/- 0.5%. Poorly differentiated tumors averaged 7.6 +/- 3.9% labeling versus 4.6 +/- 1.3% in moderately differentiated tumors, and well differentiated tumor in the series had a PCNA labeling index of 2.5 +/- 0.9%. The PCNA labeling indices for atypical hyperplasia were 1.9, and 4.1%, respectively. Our preliminary results suggest that the measurement of PCNA labeling index in prostate cancer may prove to be a new objective and quantitative assay of biological potential of individual tumor.

A model of localized osteolysis induced by the MBT-2 tumor in mice and its responsiveness to etidronate disodium

SummaryA new experimental method to test the effect of drugs on tumor-induced osteolysis using a bladder tumor in mice has been designed. The method consistsed of inoculating MBT-2 tumor cells s.c. over the calvaria in mice, resulting in a local tumor causing fragmentation of the bone. This was accompanied by adjacent osteoplastic changes, which were evaluated by X-ray and histological examination. Etidronate disodium (EHDP), a diphosphonate derivative, at a dose of 3 mg/kg to 30 mg/kg s. c. protected the bone by decreasing the extent of osteolysis as judged by the same criteria. Therapy with EHDP prolonged the survival period. This inhibition was obtained with no apparent effect on the growth of the MBT-2 tumor.

Clinical significance of the vertebral vein in prostate cancer metastasis.

A total of 75 prostate cancer and 67 lung cancer patients with positive bone scintigrams were studied. The patterns of spread in the axial skeleton and pelvis were different between the groups. The differences in the distribution of bony metastases between prostate and lung are explained by the role of Batsons vertebral venous plexus. We developed an animal model of spinal bone metastasis to prove this route. As suspension of tumor cells was injected into the tail vein of mice with vena caval occlusion. This procedure reproducibly resulted in metastatic tumor growth in the lumbar region of the vertebral column. The prevalence of spinal bone metastasis is attributed to passage of tumor cells via the vertebral venous plexus.

Hamartoma of the urinary bladder

Background: Hamartomas of the urinary bladder are extremely rare. We report on a case in a 58‐year‐old female who presented with the chief complaint of pain on urination.

Prognostic Significance of Nucleolar Organizer Region (AgNOR) in Renal Cell Carcinoma

PURPOSEnEvaluation of prognostic significance of nucleolar organizer regions (NORs) in renal cell carcinoma (RCC).nnnMATERIALS AND METHODSnNuclear organizer regions were quantified in a series of 59 cases of RCC by the silver colloid method, and the NOR index was obtained from the ratio between mean NOR counts in each neoplastic nucleus and in normal nucleus. The patients were staged pathologically and divided into 2 groups by average NOR index of all cases, which was 0.76. Correlations between the NOR index and other parameters were statistically analyzed, and the prognostic value of the NOR index was also examined.nnnRESULTSnThe NOR indices from each group were correlated with the survival curve. In low stage tumors (pT1 or 2 N0M0), the low NOR index group had a survival rate of almost 100 per cent while in those patients with higher NOR indices, there was a significantly increased mortality (p < 0.01). In patients presenting with high stage tumors (excluding pT1 and 2 N0M0), the survival rate was significantly improved in those patients with a low NOR index (p < 0.01). On the other hand, the patients with a low NOR index have a better prognosis than those with a high NOR index within each tumor grade (p < 0.01). Statistical analysis by the log rank test indicated NORs to be a significant predictor of survival over the whole series within low and high pathological stages and within each tumor grade. Analysis of the data with Coxs proportional hazard model showed that NOR index had a stronger hazard ratio than grade or stage of tumor (p = 0.0005).nnnCONCLUSIONSnOur study has demonstrated that NOR index is a new prognostic indicator for patients with RCC (p = 0.0005).

Adrenal Myelolipoma Associated with Hereditary Spherocytosis

Myelolipomas are benign tumors composed of mature fat and bone marrow elements. We report a case of adrenal myelolipoma associated with hereditary spherocytosis which was treated with splenectomy seventeen years ago. The hematopoietic stimulus of the hereditary spherocytosis might have been associated with the development of adrenal myelolipoma in the present case.

Evaluation of nucleolar organizer regions in human bladder cancers by light- and electron-microscopic morphometry.

The number of nucleolar organizer regions (NOR) of human bladder cancers was evaluated at the light- and electron-microscopic level. The average number of argyrophilic NOR (AgNOR), stained by the one-step silver colloid method, was measured in benign and malignant urothelial cells in the human urinary bladder using a light microscope. The average number of nucleolar fibrillar centers (FC) per nucleus was also calculated by quantitative ultrastructural morphometry in the specimens from the same patients. Statistical evaluations revealed that the average number of AgNOR per nucleus was significantly correlated with the elevation of tumor grade and stage (p < 0.05). An average FC number per nucleus also increased in association with tumor grade and stage (p < 0.05). Although the average number of FC was 5.6 times higher than that of AgNOR, the correlation between the average number of FC and AgNOR was statistically significant. In conclusion, these results suggested that the silver staining method was a useful and convenient tool for the evaluation of the differentiation and invasive potential of bladder cancer cells at the light-microscopic level.

Experience with gleason histopathologic grading of prostatic cancer in Japan

Histologic characteristics of prostate cancer in Japan were evaluated in a retrospective analysis of 267 cases. These specimens were graded by the Gleason histopathologic grading system, and the proportional distribution of histologic features and the death rate were compared with those of Gleasons results in the literature. The system demonstrates significant correlation with mortality rates for each grade group in our cases, and it was also found that the death rates as obtained by our figures were comparable to those of Gleason in each category. The results help to provide the basis for future comparative multinational trials of prostate cancer.