This WHO/ISUP system is an attempt to develop as broad a consensus as possible in the classification of urothelial neoplasms, building upon earlier works and classification systems. It is meant to serve as a springboard for future studies that will help refine this classification, thus enabling us to provide better correlation of these lesions with their biologic behavior using uniform terminology.

One hundred and one cases of clinical prostatic carcinoma (PCa), primary site, were analysed to define the interrelationship between tumour angiogenesis, histological grade, and bone marrow metastasis. Tumour angiogenesis was determined by the blood capillary density ratio (BCDR; a/b), defined as the ratio between the area of the blood capillaries (a) and the area of the tumour (b). The BCDR was evaluated by a colour image analysis system employing a computerized morphometrical method. A total of 43 cases of PCa with bone marrow metastasis (stage D2) and 58 cases of PCa without metastasis (stage B, C) were utilized. The prostatic carcinomas were classified into three groups (low, intermediate, and high) using Gleason's grading system. The BCDR of the primary PCa with bone marrow metastasis was similar in each of the three histologically graded scores. On the other hand, in the cases of PCa without metastasis, the BCDR of high score PCa was higher than those of the low and intermediate score PCa (U-test; P < 0.001). The BCDR of the high score PCa without metastasis was similar to that of the PCa with bone marrow metastasis. The BCDR may provide help in predicting tumour progression with regard to bone marrow metastasis of PCa with low and intermediate Gleason's scores.

Endothelial cells and pericytes play critical role in angiogenesis, which is controlled, in part, by the angiopoietin (Ang)/Tie-2 system and vascular endothelial growth factor (VEGF). Here, we investigated Ang, Tie-2, and VEGF expression within endothelial cells and pericyte interdigitations (EPI), which consist of cytoplasmic projections of pericytes and corresponding endothelial indentations. After subcutaneous implantation of a thermoreversible gelation polymer disc in rats, the capillary density was low on day 5, increased to a peak on day 7, and then decreased on days 10-20. A small number of EPI were observed on day 5, then increased sharply to a peak on day 10, but had decreased on day 20. Light and electron microscopy immunohistochemical and RNA in situ hybridization analyses revealed that Tie-2 localized at endothelial cells, and Ang-2 localized at endothelial cells and pericytes, while Ang-1 and VEGF localized at pericytes, and Ang-1 was most intensely observed at EPI of pericytes. Conventional quantitative RT-PCR and Western blot analyses revealed that the level of Ang-1 was low on days 5-7, then increased on days 10-20, while the level of VEGF was high on days 5-10, but had decreased on day 20. The level of Ang-2 remained high and Tie-2 remained at the level of the control on days 5-20. The present study showed that the angiogenic phase might be initiated by increases in Ang-2 and VEGF, while the microvessel maturation phase might be initiated by a relative increase in Ang-1 and a decrease in VEGF. Moreover, EPI might serve as a pathway for the Ang-1/Tie-2 system, with VEGF promoting pericyte recruitment for microvascular integrity.

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Sixty-three cases of benign and malignant canine mammary tumors were analyzed to define the alteration of exons 5-8 for the p53 tumor suppressor gene using polymerase chain reaction direct sequence analysis with paraffin-embedded tissues. Four missense mutations were found in 38 benign mammary tumors (11%), and five missense (one tumor had two missense mutations) and one nonsense mutations were found in 25 mammary carcinomas (20%). These data suggest that the p53 gene alterations might be initiated at an early stage of canine mammary carcinogenesis and p53 mutations might be associated with malignancy. However, there was no evidence of any relationship between the p53 alterations and the histologic types of tumors or breeds of dogs.