Cyclin D1 contributes to regulate G1 progression by forming a complex with different cyclin-dependent kinases. It has oncogenic properties and is frequently overexpressed in several human tumor types. In our study, expression of cyclin D1 and Ki67, a proliferation marker, was evaluated by immunohistochemistry in human papillary superficial (pTa-pT1) bladder cancers and was correlated with p27 Kip1 , p21 Waf1 and c-erbB-2 expression, with p53 gene status and protein expression, ploidy and cancer progression. Cyclin D1 expression was neither associated with tumor stage nor with tumor grade but high cyclin D1 expression (>25% positive nuclei) was significantly associated with p53 gene mutation (p ‫؍‬ 0.012), low p21 Waf1 (p ‫؍‬ 0.015) and high p27 Kip1 (p ‫؍‬ 0.016) protein expression. Ki67 expression was not associated with tumor stage but a high proliferation index (>10% positive nuclei) was significantly associated with high tumor grade (p ‫؍‬ 0.001) and with DNA aneuploidy (p ‫؍‬ 0.005). There was no significant difference in proliferative activity between high and low cyclin D1 expressor tumors. Patients whose tumors showed high expression of cyclin D1 displayed a significantly longer disease-free survival (p < 0.001 by log-rank test). Increased Ki67 expression was significantly associated with shorter disease-free survival (p ‫؍‬ 0.003). Both cyclin D1 (p ‫؍‬ 0.027; RR ‫؍‬ 1.898) and Ki67 (p ‫؍‬ 0.047; RR ‫؍‬ 1.932) protein expressions were independent predictors of reduced diseasefree survival on a multivariate analysis that also included p27 Kip1 expression and tumor stage. The simultaneous presence of low cyclin D1, low p27 Kip1 and high Ki67 expression defined a "high-risk" group of patients who displayed a significantly increased risk of recurrence (p < 0.0001). These results suggest that evaluation of cell cycle-associated markers can help to identify high-risk patients and may affect the management of patients with papillary superficial bladder cancer.

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surgery only patients diagnosed with pT1 tumours were treated by intravesical bacille Calmette-Guérin (BCG) instillations; all received intravesical BCG if there was a recurrence. The clinicopathological variables, recurrence and disease-free interval to recurrence were assessed. Proliferative activity (MIB-1) and expression of cell-cycle regulation proteins cyclin D1, p53 and p27 kip1 were detected by immunohistochemistry in the tumours of both groups.

The increasing incidence of bladder carcinoma observed in the past three decades has stimulated research into the identification of possible aetiological agents. The possible role of viruses in this respect is still highly controversial. 1-4The significant association between human papillomavirus (HPV) infection and genital cancers in both sexes has prompted attempts to identify HPV in bladder cancers as well as in various benign lesions of the urinary tract.5 At present more than 90 distinct types of HPV have been recognised 6 7 and more than 35 of these have shown specific tropism for the male and female genitourinary tract, ensuring an easy mode of transmission between these natural reservoirs. 3 However, even in the most up to date reports there is no agreement about the occurrence of HPV in bladder carcinoma, the percentage of positive cases ranging between 0% 8-11 to 80%. 2The choice of material and the diVerent techniques performed seem to influence the number of false positive and false negative results-that is, the use of single or multiple tumour fragments, fresh or fixed and paraYn embedded material, the number of virus genotypes sought, contamination by plasmid DNA or polymerase chain reaction (PCR) products, and the use of high or low sensitivity techniques (Southern blot, PCR, or in situ hybridisation). It was against this background that we set out to determine whether the use of multiple biopsies and multiple probes in an in situ hybridisation system could increase the detection rate of HPV positive cases. At the same time, we wished to examine the possible relation between circulating anti-HPV antibody detected by an immunoenzymatic assay and the presence of HPV positive bladder cancer, identified by in situ hybridisation of HPV DNA in cancer tissues.Our final aim was to make a preliminary evaluation of the possible correlation between the presence of HPV DNA and clinicopathological indices such as grade, stage, and evolution of the neoplastic disease. MethodsBetween 1995 and 1997, we carried out enzyme linked immunosorbent assays (ELISA) for serum antibodies against human and bovine papillomaviruses in 43 patients with transitional cell papillary carcinoma of the urinary bladder at the time of diagnosis (38 males, five females, age range 36 to 85 years, mean (SD) age 66.3 (19.8) years). Twenty seven of these were serum antibody positive, 13 were serum negative, and three were classified as uncertain, with antibody titres that were barely above the cut oV point. The

We describe the case of a 46-yr-old euthyroid woman, who was submitted to right lobectomy plus isthmusectomy because of a 30 mm large, rapidly growing thyroid nodule. Two cytological examinations of fine needle aspiration biopsy (FNAB) specimens were not diagnostic. Histology showed a neoplasm composed of nests of chief cells, almost completely replacing thyroid parenchyma, infiltrating the capsule and surgical resection margins, and invading perithyroid tissues. Immunohistochemical analysis revealed that the tumor stained positively to chromogranin, synaptophysin, NSE, S-100 protein and tyrosine hydroxylase, whereas no immunoreactivity was detected against cytokeratin, thyroglobulin, TTF-1, calcitonin and CEA. A diagnosis of thyroid paraganglioma (PG) was finally made. No complications developed following operation. Laboratory analysis and imaging study excluded multicentric disease, metastases to neck or extracervical organs, and multiple endocrine neoplasia (MEN). We report this unusual case, underscore its clinical and immunohistochemical features and discuss differential diagnosis.