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The TMPRSS2-ERG fusion has been reported in 42 to 78% of prostate tumors. More than 90% of ERG-overexpressing tumors harbor the fusion. The relationship between the TMPRSS2-ERG fusion and prognosis is controversial. Different studies have suggested an association between CXCR4 and ERG overexpression resulting from the TMPRSS2-ERG rearrangement. The aim of this study was to investigate the relationship between CXCR4 expression, TMPRSS2-ERG fusion and Gleason grade in prostate cancer. TMPRSS2-ERG rearrangement was investigated by FISH (n=44), ERG protein by IHC (n=84), and CXCR4 by quantitative RT-PCR (n=44). TMPRSS2-ERG rearrangement and ERG protein expression were present in almost 50% of the cases, without statistical differences between the different Gleason score groups. There was a very high concordance between FISH and IHC techniques (Kappa Index=0.954). Seventy percent of Gleason &ges; 8 prostate tumors overexpressed CXCR4 mRNA, and the difference in CXCR4 expression with Gleason < 8 cases was statistically significant (p=0.009). There was no association between ERG protein and CXCR4 mRNA expression. In conclusion, our results reveal for the first time that CXCR4 overexpression is associated with high Gleason score prostate tumors, but that it is independent of the TMPRSS2-ERG rearrangement. [ABSTRACT FROM AUTHOR]

Background Previous evidence suggests that 25-hydroxyvitamin D3 [25(OH)D3 ] protects against several cancers. However, little is known regarding urothelial bladder cancer (UBC). We analyzed the association between plasma 25(OH)D3 and overall risk of UBC, as well as according to stage and FGFR3 molecular subphenotypes. Methods Plasma concentrations of 25(OH)D3 in 1125 cases with UBC and 1028 control subjects were determined by a chemiluminescence immunoassay. FGFR3 mutational status and expression in tumor tissue were assessed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression adjusting for potential confounders. Analyses were further stratified by tumor invasiveness and grade, FGFR3 expression, and smoking status. Cell proliferation was measured in human UBC cell lines cultured with 1α,25-dihydroxyvitamin D3. Results A statistically significantly increased risk of UBC was observed among subjects presenting the lowest concentrations of 25(OH)D3 (ORadj 1.83; 95% CI = 1.19 to 2.82; P= .006), showing a dose-response effect (Ptrend = .004).The association was stronger for patients with muscle-invasive tumors, especially among Iow-FGFR3 expressers (ORadj = 5.94; 95% CI = 1.72 to 20.45; P= .005).The biological plausibility of these associations is supported by the fact that, in vitro, 1α,25-dihydroxyvitamin D3 upregulates FGFR3 expression in UBC cell lines with low levels of wild-type FGFR3. Conclusion These findings support a role of vitamin D in the pathogenesis of UBC and show that 25(OH)D3 levels are associated with FGFR3 expression in the tumor. Because FGFR3 mutation and overexpression are markers of better outcome, our findings suggest that individuals with low levels of plasma 25(OH)D3may be at high risk of more aggressive forms of UBC. [ABSTRACT FROM AUTHOR]

Background: Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the in vivo behavior of these phenomena within the same bladder tumor. Methods: Twenty-one paraffin-embedded bladder tumors were analyzed by conventional comparative genome hybridization and fluorescence in situ hybridization (FISH) with a cyclin D1 gene (CCND1)/centromere 11 dual-color probe. Immunofluorescent staining of α, β and γ tubulin was also performed. Results: Based on the CIN index, defined as the percentage of cells not displaying the modal number for chromosome 11, tumors were classified as CIN-negative and CIN-positive. Fourteen out of 21 tumors were considered CIN-positive. All T1G3 tumors were included in the CIN-positive group whereas the majority of Ta samples were classified as CIN-negative tumors. Centrosome clustering was observed in six out of 12 CIN-positive tumors analyzed. CCND1 amplification in homogeneously staining regions was present in six out of 14 CIN-positive tumors; three of them also showed amplification of this gene in double minutes. Conclusions: Complex in vivo behavior of CCND1 amplicon in bladder tumor cells has been demonstrated by accurate FISH analysis on paraffin-embedded tumors. Positive correlation between high heterogeneity, centrosome abnormalities and CCND1 amplification was found in T1G3 bladder carcinomas. This is the first study to provide insights into the coexistence of CCND1 amplification in homogeneously staining regions and double minutes in primary bladder tumors. It is noteworthy that those patients whose tumors showed double minutes had a significantly shorter overall survival rate (p < 0.001). [ABSTRACT FROM AUTHOR]

The genes encoding tyrosine kinase receptors EphB2 and EphB3 are β-catenin and Tcf4 target genes in colorectal cancer (CRC) and in normal intestinal cells. In the intestinal epithelium, EphB signaling controls the positioning of cell types along the crypt-villus axis. In CRC, EphB activity suppresses tumor progression beyond the earliest stages. Here we show that EphB receptors compartmentalize the expansion of CRC cells through a mechanism dependent on E-cadherin–mediated adhesion. We demonstrate that EphB-mediated compartmentalization restricts the spreading of EphB-expressing tumor cells into ephrin-B1–positive territories in vitro and in vivo. Our results indicate that CRC cells must silence EphB expression to avoid repulsive interactions imposed by normal ephrin-B1–expressing intestinal cells at the onset of tumorigenesis. [ABSTRACT FROM AUTHOR]

Cystic tumors of the pancreas are uncommon. They account for 10–15% of all pancreatic cystic masses and only 1% of pancreatic malignancies. Mucinous cystadenocarcinoma is the most frequent pancreatic cystadenocarcinoma and it is mainly seen in women, suggesting a sex hormone influence. Its presentation during pregnancy is infrequent and entails difficult diagnostic and therapeutic decisions. We report the case of a 31-year-old woman who presented a pancreatic cystadenocarcinoma 2 months after delivery. A 31-year-old woman was referred to our service because of abdominal pain and mass. She had given birth to her first child 2 months previous. Abdominal ultrasound demonstrated a poorly circumscribed cystic mass in the left upper abdominal quadrant, and the computed tomography scan showed a multilocular cystic lesion located in the body of pancreas. There was no seric alteration of specific pancreatic enzymes or tumor markers. Laparoscopic examination showed a large cystic tumor (12 × 11 × 5.5 cm) in the pancreas involving the body and the tail. It extended to the spleen and was highly vascularized, precluding a minimal invasive resection. An open body–tail pancreatectomy and splenectomy was performed. The resection margins were free of tumor, and the histological study showed a mucinous pancreatic cystadenocarcinoma with mucin-producing columnar epithelium and associated papillae patterns, reminiscent of ovarian stroma. Immunohistochemical studies were negative for hormonal receptors. The patient had no post-surgical complications and was discharged home in 4 days. Cystic tumors of the pancreas are infrequent, and cancer of the pancreas during pregnancy is extremely rare. Insidious symptoms and bodily changes due to pregnancy may mask diagnosis. Aggressive surgery is currently the only chance of cure. [ABSTRACT FROM AUTHOR]

The article reports on the case of male renal transplant recipient with persistent bilateral masses over both legs which appeared a year before the consultation. The medical history of the patient included arterial hypertension, hepatitis C virus infection and chronic renal failure of unknown origin. The patient had undergone dialysis treatment preceding a heterotopic kidney transplant. He is following treatment with cyclosporine, deflazacort and nifedipine. His physical examination revealed masses below the knees above the ankles. The masses showed fluctuation after pressure which suggest a synovial origin.

Abstract: We report the case of a 43-year-old male with multiple tumor foci showing microscopic features of chromophobe renal carcinoma (ChRCC) arising in an oncocytoma. Conventional cytogenetics of fresh tumor cells and fluorescence in situ hybridization (FISH) revealed the following abnormal karyotype: 46,XY,der(8)ins(8;11)(p?;q13),der(11)ins(8;11)inv(11)(q12?p15) with CCND1 (11q13) rearrangement. To our knowledge, chromosome 8 has not been reported as a partner involved in structural rearrangements of 11q13 in oncocytomas. FISH in paraffin tissue sections revealed a rearrangement of CCND1 (11q13) in the oncocytoma cells. The multiple foci of chromophobe carcinoma presented multiple copies of CCND1, suggesting that they represented a transformation from oncocytoma into ChRCC. There was immunohistochemical overexpression of CCND1 in both oncocytoma and chromophobe carcinoma cells. In this case, the correlation of the microscopic findings with changes in CCND1 gene associated to CCND1 overexpression in both components suggest that the ChRCC would have originated from the preexisting oncocytoma. It is not possible to detect, by cytogenetic techniques alone, if the ChRCC component have also the CCND1 rearrangement in addition to the detected polysomy. FISH techniques on paraffin tissue sections may help to identify genetic aberrations such as CCND1 rearrangement in order to establish a diagnosis of oncocytoma. [Copyright &y& Elsevier]