Juxtaglomerular cell tumor: a morphological, immunohistochemical and genetic study of six cases.

Juxtaglomerular cell tumors (JGCTs) are rare tumors characterized by renin synthesis, hyperaldosteronism and hypertension. A curious immunohistochemical overlap between JGCT and gastrointestinal stromal tumor (GIST) including the expression of vimentin, CD34, CD117, α-smooth muscle actin was previously reported, prompting us to further investigate JGCT and its phenotypic and molecular genetic characteristics. Virtual karyotyping showed gain of chromosomes 3, 4, 10, 13, 17 and 18 in one JGCT, and fluorescence in situ hybridization (FISH) study confirmed this multiple gain pattern. Additionally, loss of chromosome 9 was observed in four of six cases analyzed with FISH. A whole genome expression analysis revealed 415 up-regulated (including renin, and CD117) and 325 down-regulated genes between the 2 cases. The study confirmed earlier reports on the gain of chromosomes 4 and 10, and provided further evidence of up-regulation of the genes located on these 2 chromosomes. For the first time our study indicated the importance of the loss of chromosome 9 and loss of expression of several tumor suppressor genes located on this chromosome as possible pathogenetic events important in development of JGCT.

Altered expression of UPIa, UPIb, UPII, and UPIIIa during urothelial carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in rats.

In normal urothelium, superficial umbrella cells express four major integral membrane proteins, uroplakins UPIa, UPIb, UPII, and UPIIIa, which compose urothelial plaques. In the apical plasma membrane, urothelial plaques form microridges. During neoplastic changes, microridges are replaced by microvilli, while uroplakin expression is retained. We correlated individual uroplakin expression with apical plasma membrane structure, cytokeratin 20 expression, and urothelial cell proliferation (Ki-67). Male Wistar rats were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water, which caused flat hyperplasia with mild dysplasia, low-grade papillary urothelial carcinoma, invasive low- and high-grade papillary urothelial carcinoma and invasive squamous cell carcinoma with extensive keratinization, grade 2. During urothelial carcinogenesis, UPII expression was the most decreased in all urothelial lesions, while UPIa, UPIb, and UPIIIa expression was differently altered in different types of lesions. Superficial cells were covered with microvilli and ropy ridges, while microridges were disappearing. The expression of cytokeratin 20 was decreased and limited to superficial urothelial cells. Proliferation indices were increased, except for invasive squamous cell carcinoma with extensive keratinization. Our results indicate that during urothelial carcinogenesis the expression of UPII is diminished, suggesting that UPIb/UPIIIa heterodimer can still be formed, while heterodimer UPIa/UPII formation is disrupted. Correlation between decreased level of UPII expression and changed apical plasma membrane structure suggests that diminished expression of UPII hinders the urothelial plaque formation.

Multifocal hepatoblastoma in a 6-month-old girl with trisomy 18: a case report.

INTRODUCTION: Edward's syndrome (trisomy 18) is a rare entity with a reported incidence of 1/3000 to 1/7000 births. Less than 10% of patients survive beyond the first year of life, which may influence the fact that malignant tumors are rarely reported in association with this syndrome. CASE PRESENTATION: The authors report a rare case of a 6-month-old girl with trisomy 18 and multifocal hepatoblastoma. The course of the disease, autopsy results and review of the literature are presented. CONCLUSION: Our case represents the seventh published case of hepatoblastoma in a patient with trisomy 18. All of the seven published cases were women, possibly due to the high preponderance of females among the children with Edward's syndrome and longer survival of females with trisomy 18 compared to males. Since both trisomy 18 and hepatoblastoma are rare conditions, the probability that a child with trisomy 18 will independently develop a hepatoblastoma is very low. Therefore, we believe that the existence of these cases in children with trisomy 18 indicates a significant association. It can be assumed that trisomy 18 potentiates the development of hepatoblastoma. Careful clinical and post-mortem studies are needed to recognize the real frequency of hepatoblastoma in children with trisomy 18, who might die from different causes with unrecognizable hepatoblastoma.

Tissue ischemia due to CO2 pressure during laparoscopic radical prostatectomy.

Laparoscopic radical prostatectomy is nowadays one of the most frequently performed urological surgical procedures. For insufflation in laparoscopic radical prostatectomy (LRP) CO2 is used, with the pressure in the operative region between 12 and 15 mm Hg. At the microcirculation level, the pressure is lower, which raises the possibility of ischemic tissue damage during the procedure. The activity of glutathione peroxidase (GSH-px), superoxide dismutase (SOD) and catalase (CAT) was measured at the beginning and immediately after the end of the surgery in 44 patients who underwent LRP and in 11 who underwent retropubic radical prostatectomy (RRP). Capillary endothelial damage was assessed by applying immunohistochemical and morphometric methods to tissue samples from the urinary bladder neck, which contains all layers of the bladder wall. Measurement of the enzyme activity showed no significant increase of GSH-px (p-0.431), SOD (p-0.220) and CAT (p-0.434) levels. Neither immunohistochemical analysis of the bladder neck capillaries with i-nitric oxide synthase (i-NOS) nor morphometric analysis showed signs of endothelial ischemic damage.

The presence of the CYP11A1 (TTTTA)6 allele increases the risk of biochemical relapse in organ confined and low-grade prostate cancer.

The involvement of the CYP11A1 gene in the synthesis of androgens makes it a compelling candidate for various hormone-dependent diseases, including prostate cancer. A microsatellite polymorphism (TTTTA)n in the promoter region of the CYP11A1 gene has been reported to be associated with an increased risk of metastatic and high-grade prostate cancer. In the present study of 110 prostate cancer patients and 96 population controls, we examined the association between the CYP11A1 (TTTTA)n polymorphism and prostate cancer risk, aggressiveness, and incidence of biochemical relapse after prostatectomy. We have also evaluated the potential of the (TTTTA)n polymorphism as a microsatellite marker for the detection of genomic instability in prostate cancer. A strong association of the genotype containing the (TTTTA)6 allele with the occurrence of biochemical relapse after prostatectomy in patients with organ confined prostate cancer (p<0.0001), as well as in patients with low-grade prostate cancer (p=0.002) or both (p<0.0003) was determined. The incidence of biochemical relapse in patients with organ confined and low-grade prostate cancer in our study group was 22%, but increased to 50% in carriers of the (TTTTA)6 allele. Our findings also suggest (TTTTA)n instability as a potential marker for the detection of early events in carcinogenesis.

Transitional cell carcinoma involving the ureterovesical part of a transplanted ureter.

Ureterovesical malignancy in the renal transplant recipient is an infrequent occurrence. We report a woman with a cadaver kidney recipient, transplanted 10 years ago, with transitional-cell carcinoma at the ureterovesical part of the transplanted ureter invading the bladder muscle around the orifice. Though aggressive surgery and chemotherapy of such patients is proposed, most patients die after an average of 16-17 months. In our patient we have done partial ureter and bladder resection in order to preserve kidney graft and bladder. We continued immunosuppressive treatment. The patient has survived 16 months and is symptom free. Our case suggests that nonaggressive operative treatment without chemotherapy in selected patients may provide comparable survival to patients with aggressive treatment, but with better quality of life.