Youn-Wha Kim

Expression of the human erythrocyte glucose transporter in transitional cell carcinoma of the bladder

OBJECTIVES It has previously been shown that glucose uptake and use is more prevalent in carcinomas than in normal cells and tissues. We hypothesized that human erythrocyte glucose transporter (Glut-1) expression is increased in bladder transitional cell carcinoma (TCC) and that the grade of expression might correlate with the degree of malignancy. METHODS Immunostaining of Glut-1 protein was studied in normal bladder (5 cases), benign papilloma (10 cases), superficial tumor (48 cases), and invasive tumor (31 cases) tissue. The immunoreactivity grading system used was as follows: absence of immunoreactivity in tumor cell = 0; less than 10% of the tumor cells immunoreactive = 1+; 10% to 50% of the tumor cells immunoreactive = 2+; and greater than 50% of the tumor cells immunoreactive = 3+. RESULTS Immunostaining of Glut-1 protein was not expressed in the normal bladder or benign papilloma samples, but it was expressed in 63.0% (46 of 73) of the TCC samples. In the pattern of expression of Glut-1 protein, superficial TCC was stained focally, but invasive TCC was stained diffusely in the tumor nests. The grade of Glut-1 protein expression increased more significantly in the invasive TCC than in the superficial TCC samples (P = 0.002) and more significantly in the high nuclear grade than in the low nuclear grade samples (P = 0.007). In the superficial TCC samples, the bladder tumor recurrence rate did not significantly correlate with Glut-1 protein expression (P = 0.40). CONCLUSIONS Our results suggest that the Glut-1 protein is not expressed in normal bladder mucosa and benign lesions, that Glut-1 protein expression is strongly associated with neoplastic progression in bladder TCC, and that Glut-1 expression does not correlate with the recurrence rate in superficial bladder TCC.

Neurilemmoma of the mandible

Abstract Intraosseous neurilemmoma is rare, representing less than 1% of benign primary bone tumors. The site most commonly involved is the mandible. We report on a neurilemmoma of the mandible in a 30-year-old woman. A panoramic radiograph of the mandible showed a well-defined unilocular osteolytic lesion with a thin uniform sclerotic margin located in the body of the mandible. The CT scan confirmed a well-defined osteolytic lesion with thinning of the cortex of the body of the left side of the mandible. Histologically, the lesion was a moderately cellular neoplasm with distinct palisading and numerous Verocay bodies. Ultrastructurally, the cytoplasmic membranes were distinct and coated by amorphous bands of basal lamina. Complete excision was achieved by removing the tumor from the inferior alveolar nerve.

Low expression of p63 and p73 in osteosarcoma.

Background The recent discovery of two p53-related genes, p63 and p73, has revealed an additional level of complexity to the study of p53 function. Both genes encode multiple proteins arising from alternative promoter usage and splicing, with transactivation, DNA-binding, and tetramerization domains. Recent data support a role for p63 in squamous and transitional cell carcinomas, as well as in certain lymphomas and thymomas. Methods To characterize the involvement of p63 and p73 in the development of osteosarcoma, we analyzed the expression and mutation of TAp63 and TAp73 in six osteosarcoma cell lines and twelve osteosarcoma specimens. Results Semiquantitative DNA/PCR analysis revealed that eight (67%) and six (50%) out of twelve osteosarcoma specimens showed significantly reduced levels of p63 and p73 transcription, respectively. Direct sequencing of the entire coding region detected no mutations in cell lines or osteosarcoma specimens. Conclusions Our data suggest that low expression of p63 and p73 is relatively common in osteosarcomas and might contribute to their molecular pathogenesis.

Liver cirrhosis developed after ketoconazole‐induced acute hepatic injury

Abstract  We describe a previously healthy woman who developed liver cirrhosis as a sequela of acute hepatic injury that was induced by ketoconazole administration to treat onychomycosis. The initial presentation of the disease was of a typical acute hepatitis, characterized by nausea, anorexia, fatigue, and jaundice that developed during the administration of ketoconazole. Many other causes of hepatitis were absent in the patient. Even though the hepatic injury was gradually resolved for several months after cessation of the drug, the liver function was not completely restored. Six months after the onset of illness, a follow‐up abdominal computed tomography and peritoneoscopic liver biopsy were performed. They revealed a marked reduction in the liver volume and a definite cirrhotic change, which persisted for more than 5 years. The case suggests that the administration of ketoconazole can cause liver cirrhosis through acute hepatic injury within a short time under certain circumstances.

Is chronic inflammatory change in the prostate the major cause of rising serum prostate‐specific antigen in patients with clinical suspicion of prostate cancer?

Aim:  To evaluate the cause of elevated prostate‐specific antigen (PSA) in patients with transrectal needle biopsy negative for prostate cancer.

Clinical significance of urinary vascular endothelial growth factor and microvessel density in patients with renal cell carcinoma.

OBJECTIVES To investigate the urinary vascular endothelial growth factor (VEGF) levels from patients with renal cell carcinoma (RCC). Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors. VEGF is thought to exert potent angiogenic activity. METHODS Urine samples were obtained before radical nephrectomy from 27 patients with RCC and 10 control subjects with no evidence of cancer or inflammatory disease. VEGF was measured by enzyme-linked immunosorbent assay in the urine and corrected according to the 24-hour urine concentration of creatinine. The microvessel density was measured by immunohistochemical staining with CD31 monoclonal antibody. Nuclear morphometry was performed by photomicroscopy. RESULTS The corrected urinary VEGF levels in patients with RCC were much higher than those in the normal control group (P = 0.039) and were more elevated in patients with higher stages of RCC (Stages III and IV versus Stages I and II; P = 0.024). A tendency was also noted for the VEGF levels to be higher according to cell grade. However, no statistical correlation was found between the corrected urinary VEGF and age, sex, tumor size, cell type, microvessel density, platelet count, or hemoglobin. The nuclear area was higher with more advanced-stage tumors (P = 0.043) and tended to increase according to the tumor cell grade. CONCLUSIONS The results of this study indicate that urinary VEGF levels are increased in patients with RCC. However, they may not reflect the underlying angiogenic activity, and it may be that other angiogenic factors play a more prominent role.

Expression and prognostic significance of human growth and transformation-dependent protein in gastric carcinoma and gastric adenoma☆

Human growth and transformation-dependent protein is a hypoxia-responsive, proapoptotic protein downstream of hypoxia-inducible factor 1alpha. Its function and expression pattern in human cancers are largely unknown. We investigated the expression profile of human growth and transformation-dependent protein using immunohistochemistry in gastric tissues including cancer (n = 138), adenoma (n = 37), intestinal metaplasia (n = 20), and normal gastric epithelium (n = 20), then correlated human growth and transformation-dependent protein expression in tumors with clinicopathologic features. Human growth and transformation-dependent protein showed strong staining in the cytoplasm of intestinal-type adenocarcinoma and gastric adenoma, whereas normal gastric antral mucosa showed no staining. Human growth and transformation-dependent protein expression in gastric cancer showed a close association with the Lauren classification, tumor stage, and Ki-67 proliferation index. These findings suggest that human growth and transformation-dependent protein expression is a common occurrence during the progression from a normal gastric mucosa to an intestinal-type carcinoma and may be associated with tumor cell proliferation activity.

Glucose Transporter-1 Expression in Urothelial Papilloma of the Bladder

Introduction: Urothelial papilloma should be distinguished from low-grade urothelial carcinoma. We report our experience with glucose transporter-1 (Glut-1) expression in urothelial papilloma. Materials and Methods: From January 1987 to December 2002, 32 patients with papilloma were diagnosed. Glut-1 protein expression was studied in 32 cases of papilloma and 30 cases of carcinoma. Clinical information was obtained by chart review. Results: Mean age was 54.7 years, and the solitary lesion was 78.1%. No case of bladder papilloma expressed Glut-1 protein even in cases of recurrent papilloma. However, 67% of urothelial carcinoma specimens were stained for Glut-1 protein. Two patients developed recurrent papilloma (6.2%), 1 of whom (3.1%) developed an urothelial carcinoma 4 years after diagnosis of papilloma. Conclusions: The study showed that papilloma does not express the Glut-1 protein in contrast to urothelial carcinoma. This distinctive expression pattern of Glut-1 will possibly contribute to differentiate urothelial papilloma from low-grade urothelial carcinoma.

Autoimmune cholangitis in a patient with thymoma.

Abstract  Autoimmune cholangitis is characterized biochemically by chronic cholestasis and histopathologically by chronic non‐suppurative destructive cholangitis. It is associated with positive antinuclear antibody test and negative antimitochondrial antibody test results. Recently, we experienced a case of a 35‐year‐old woman with autoimmune cholangitis associated with thymoma who presented with pruritis, jaundice, chronic fatigue and anterior chest discomfort. Her laboratory examinations revealed marked increases in levels of serum alkaline phosphatase and gamma‐glutamyl transpeptidase. In serological tests, antinuclear antibody was found, but antimitochondrial antibody was not. Liver biopsy findings were compatible with chronic non‐suppurative destructive cholangitis. On computed tomography (CT) of the chest, a large anterior mediastinal mass was found. The mass was totally resected and the patient was treated with ursodeoxy cholic acid. Thereafter, her clinical symptoms improved and liver functions completely returned to the normal range. We describe here an uncommon association of autoimmune cholangitis with thymoma, which has not been reported previously in the English‐written literature.

Down-regulation of osteoprotegerin expression as a novel biomarker for colorectal carcinoma

A better understanding of tumor biology is important in the identification of molecules that are down-regulated in malignancy and in determining their role in tumor suppression. The aim of this study was to analyze osteoprotegerin (OPG) expression in colorectal carcinoma (CRC) and to investigate the underlying mechanism for changes in the expression of OPG. OPG expression was assessed in CRC tissue samples and cell lines. The methylation status of the OPG promoter region was determined, and the effects of demethylation on OPG expression were analyzed. The effects of recombinant OPG (rOPG) administration on cellular functions were also investigated. Clinical and prognostic implications of OPG protein expression in CRC patients were analyzed. The CRC tissues and cells showed significantly lower OPG expression. Pyrosequencing of OPG-silenced CRC cells revealed that the OPG gene promoter was highly methylated. Treatment with demethylating agent significantly elevated OPG mRNA and protein expression. rOPG significantly decreased cell viability and MMP-2 and VEGF-A production in CRC cells. Reduced OPG immunoreactivity was associated with aggressive oncogenic behavior in CRC. Also, OPG expression was found to be an independent predictor of recurrent hepatic metastasis and independent prognostic factor for worse survival rates. We demonstrated that OPG silencing in CRC occurs through epigenetic repression, and is involved in the development and progression of CRC. Our data suggest that OPG is a novel prognostic biomarker and a new therapeutic target for the treatment of patients with CRC.