Differential Protein Expression Patterns of HOXA13 and HOXB13 Are Associated with Bladder Cancer Progression.

Bladder cancer is a common urological cancer and has the highest recurrence rate of any cancer. The aim of our study was to profile and characterize the protein expression of homeobox A13 (HOXA13) and homeobox B13 (HOXB13) genes in Malaysian bladder cancer patients. The protein expression of HOXA13 and HOXB13 in formalin-fixed paraffin-embedded (FFPE) bladder cancer tissues was determined by immunohistochemistry (IHC) analysis. The association between HOXA13/HOXB13 protein expression and demographic/clinicopathological characteristics of the bladder cancer patients was determined by chi-square analysis. Approximately 63.6% of the bladder cancer tissues harbored high HOXA13 expression. High HOXA13 expression was significantly associated with non-muscle invasive bladder cancer, lower tumor grade, higher number of lymph node metastases, and recurrence risk. In contrast, low HOXB13 expression (including those with negative expression) was observed in 71.6% of the bladder cancer tissues analyzed. Low HOXB13 expression was significantly associated with muscle-invasive bladder cancer, higher tumor stage, tumor grade, and metastatic risk. Both HOXA13 and HOXB13 protein expression were found to be associated with bladder tumorigenesis. The putative oncogenic and tumor suppressive roles of HOXA13 and HOXB13, respectively, suggest their potential utility as biomarkers in bladder cancer.

Rare Case of Large Catecholamine Secreting Ganglioneuroma in an Asymptomatic Elderly Male.

Ganglioneuromas (GNs) are benign tumors that originate from neural crest cells, composed mainly of mature ganglion cells. These tumors, which are usually hormonally silent, tend to be discovered incidentally on imaging tests and occur along the paravertebral sympathetic chain, from the neck to the pelvis and occasionally in the adrenal medulla. Rarely, GNs secrete catecholamines.1 Adrenal GNs occur most frequently in the fourth and fifth decades of life, whereas GNs of the retroperitoneum and posterior mediastinum are usually encountered in younger adults.2 Adrenal GNs are commonly hormonally silent and asymptomatic; even when the lesion is of substantial size.3 We report an incidentally detected asymptomatic case of an adrenal ganglioneuroma with mildly elevated urinary catecholamine levels in an elderly male. After preoperative alpha blockade, the patient underwent open right adrenalectomy. Upon microscopic examination, the right adrenal mass proved to be a ganglioneuroma, maturing type and the immunohistochemistry examination showed immunoreactivity to synaptophysin, chromogranin, and CD 56, while S100 was strongly positive at the Schwannian stroma. Following resection, catecholamine levels normalized, confirming the resected right adrenal ganglioneuroma as the source of the catecholamine excess. This case represents a rare presentation of catecholamine-secreting adrenal ganglioneuroma in the elderly.

Evaluation of CERS2 Gene as a Potential Biomarker for Bladder Cancer.

The ceramide synthase 2 (CERS2) gene has been linked to tumour recurrence and invasion in many different types of cancers including bladder cancer. In this study, the expression levels of CERS2 in bladder cancer cell lines were analysed using qRT-PCR and the protein expression in clinical bladder cancer histopathological specimens were examined via immunohistochemistry. The potential utility of CERS2 as a predictive biomarker of response to oncolytic virotherapy was assessed by correlating the CERS2 mRNA expression to IC50 values of cells treated with the Newcastle disease virus (NDV), AF2240 strain. This study demonstrates that CERS2 is differentially expressed in different types of bladder cancer cell lines and that the siRNA-mediated downregulation of the expression of CERS2 reduces the migratory potential of UMUC1 bladder cancer cells. However, there were no significant correlations between the expression levels of the CERS2 protein with bladder cancer grade/stage or between the IC50 values of cells treated with NDV and CERS2 expression. Although the utility of CERS2 expression may be limited, its potential as an antimigration cancer therapeutic should be further examined.

Giant Intradiverticular Bladder Tumor.

BACKGROUND Intradiverticular bladder tumors are rare. This renders diagnosis of an intradiverticular bladder tumor difficult. Imaging plays a vital role in achieving the diagnosis, and subsequently staging of the disease. CASE REPORT A 74-year-old male presented to our center with a few months history of constitutional symptoms. Upon further history, he reported hematuria two months prior to presentation, which stopped temporarily, only to recur a few days prior to coming to the hospital. The patient admitted to having lower urinary tract symptoms. However, there was no dysuria, no sandy urine, and no fever. Palpation of his abdomen revealed a vague mass at the suprapubic region, which was non tender. In view of his history and the clinical examination findings, an ultrasound of the abdomen and computed tomography (CT) was arranged. These investigations revealed a giant tumor that seemed to be arising from a bladder diverticulum, with a mass effect and hydronephrosis. He later underwent operative intervention. CONCLUSIONS Intradiverticular bladder tumors may present a challenge to the treating physician in an atypical presentation; thus requiring a high index of suspicion and knowledge of tumor pathophysiology. As illustrated in our case, CT with its wide availability and multiplanar imaging capabilities offers a useful means for diagnosis, disease staging, operative planning, and follow-up.

Roles of MicroRNA21 and MicroRNA29a in Regulating Cell Adhesion Related Genes in Bone Metastasis Secondary to Prostate Cancer.

BACKGROUND: There is an increasing concern in the role of microRNA (miRNA) in the pathogenesis of bone metastasis (BM) secondary to prostate cancer (CaP). In this exploratory study, we hypothesized that the expression of vinculin (VCL) and chemokine X3C ligand 1 (CX3CL1) might be downregulated in clinical samples, most likely due to the posttranscriptional modification by microRNAs. Targeted genes would be upregulated upon transfection of the bone metastatic prostate cancer cell line, PC3, with specific microRNA inhibitors. MATERIALS AND METHODS: MicroRNA software predicted that miR21 targets VCL while miR29a targets CX3CL1. Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalinfixed paraffin embedded (FFPE) specimens were analysed. From the bone scan results, high grade CaP samples were further classified into CaP with no BM and CaP with BM. Transient transfection with respective microRNA inhibitors was done in both RWPE1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and transfected cell lines to measure VCL and CX3CL1 levels. RESULTS: QPCR confirmed that VCL messenger RNA (mRNA) was significantly down regulated while CX3CL1 was upregulated in all FFPE specimens. Transient transfection with microRNA inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL mRNA was significantly up regulated while CX3CL1 mRNA was significantly downregulated compared to the RWPE1 case. CONCLUSIONS: The downregulation of VCL in FFPE specimens is most likely regulated by miR21 based on the in vitro evidence but the exact mechanism of how miR21 can regulate VCL is unclear. Upregulated in CaP, CX3CL1 was found not regulated by miR29a. More microRNA screening is required to understand the regulation of this chemokine in CaP with bone metastasis. Understanding miRNAmRNA interactions may provide additional knowledge for individualized study of cancers.