Showing papers by "Min-Han Tan published in 2005"

A Molecular Classification of Papillary Renal Cell Carcinoma

Abstract: Despite the moderate incidence of papillary renal cell carcinoma (PRCC), there is a disproportionately limited understanding of its underlying genetic programs. There is no effective therapy for metastatic PRCC, and patients are often excluded from kidney cancer trials. A morphologic classification of PRCC into type 1 and 2 tumors has been recently proposed, but its biological relevance remains uncertain. We studied the gene expression profiles of 34 cases of PRCC using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both unsupervised and supervised analyses. Comparative genomic microarray analysis was used to infer cytogenetic aberrations, and pathways were ranked with a curated database. Expression of selected genes was validated by immunohistochemistry in 34 samples with 15 independent tumors. We identified two highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to three histologic subtypes: type 1, low-grade type 2, and mixed type 1/low-grade type 2 tumors. The second class, with poor survival, corresponded to high-grade type 2 tumors (n = 11). Dysregulation of G1-S and G2-M checkpoint genes were found in class 1 and 2 tumors, respectively, alongside characteristic chromosomal aberrations. We identified a seven-transcript predictor that classified samples on cross-validation with 97% accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in class 1 tumors and of topoisomerase IIalpha in class 2 tumors. We report two molecular subclasses of PRCC, which are biologically and clinically distinct and may be readily distinguished in a clinical setting.

Utility of the Health Belief Model in predicting compliance of screening in patients with chronic hepatitis B.

Abstract: Summary Background : Regular surveillance is recommended for patients with chronic hepatitis B, to select candidates for anti-viral therapy and detect early complications. However, factors that determine compliance are not well studied. Aim : To determine the utility of the Health Belief Model in explaining non-compliance, among a group of chronic hepatitis B patients for screening. Methods : A total of 192 chronic hepatitis B patients who responded to advertisement for free screening took part in a telephonic interview study. Subjects were asked about the five constructs of the Health Belief Model, and factors associated with recent screening were analysed. Results : The mean age of the subjects was 42.1 ± 0.7 years; 77% white male, and 97% Chinese. About 108 patients (56%) had recent screening. At multivariate analysis, only the ability to remember date of follow-up (OR: 4.37; 95% CI: 2.07–9.17) and the perception of having to wait a long time for venepuncture (OR: 0.38; 95% CI: 0.19–0.79) were significantly associated with recent screening. Conclusion : Future public health measures should include improving the logistics of follow-up procedures and providing reminders for screening to improve compliance.

Overexpression of glutathione s-transferase alpha in clear cell renal cell carcinoma.

Abstract: To determine its diagnostic value, we evaluated glutathione S-transferase alpha (GST-alpha) expression in a large number of renal cell carcinomas (RCCs). GST-alpha messenger RNA (mRNA) levels from 70 renal neoplasms were analyzed with complementary DNA (cDNA) microarray chips containing 21,632 cDNA clones. Furthermore, 348 primary renal tumors and 24 metastatic RCCs were subjected to immunohistochemical analysis with a GST-alpha-specific antibody. GST-alpha mRNA was elevated significantly (11.4-fold) in a majority of clear cell RCCs (28/43 [65.1%]; 28/39 [71.8%] with adjustments for informative spots) compared with other kidney tumors (1/27 [3.7%]). Strong and diffuse GST-alpha immunoreactivity was demonstrated in a majority of clear cell (166/202 [82.2%]; mean intensity, 2.41) and metastatic clear cell RCCs (17/24 [70.8%]; mean intensity, 2.62). Other renal tumor types did not exhibit significant GST-alpha immunoreactivity, confirming mRNA results. Through cDNA microarrays and immunohistochemical analysis, we demonstrated GST-alpha as a biomarker for clear cell RCCs.

Overexpression of Glutathione S-Transferase α in Clear Cell Renal Cell Carcinoma

Abstract: To determine its diagnostic value, we evaluated glutathione S-transferase α (GST-α) expression in a large number of renal cell carcinomas (RCCs). GST-α messenger RNA (mRNA) levels from 70 renal neoplasms were analyzed with complementary DNA (cDNA) microarray chips containing 21,632 cDNA clones. Furthermore, 348 primary renal tumors and 24 metastatic RCCs were subjected to immunohisto-chemical analysis with a GST-α–specific antibody. GST-α mRNA was elevated significantly (11.4-fold) in a majority of clear cell RCCs (28/43 [65.1%]; 28/39 [71.8%] with adjustments for informative spots) compared with other kidney tumors (1/27 [3.7%]). Strong and diffuse GST-α immunoreactivity was demonstrated in a majority of clear cell (166/202 [82.2%]; mean intensity, 2.41) and metastatic clear cell RCCs (17/24 [70.8%]; mean intensity, 2.62). Other renal tumor types did not exhibit significant GST-α immunoreactivity, confirming mRNA results. Through cDNA microarrays and immunohistochemical analysis, we demonstrated GST-α as a biomarker for clear cell RCCs.

Microarray gene expression profiling in subtypes of clear cell renal cell carcinoma

Abstract: A nucleic acid probe or a novel set of such probes in a microarray is provided. The probe or probe set is useful in the prognosis of patients with clear cell renal cell carcinoma (CC-RCC), wherein aggressive and non-aggressive CC-RCC tumor types are characterized by differential expression profiles of genes that hybridize with one or more of these probes. Microarrays and kits for carrying out expression profiling of tumor and normal tissue and methods of using them are disclosed.

Microarray gene expression profiling in classes of papillary renal cell carcinoma

Abstract: A nucleic acid probe or a set of such probes in a microarray is provided. The probe or probe set is used for the prognosis of patients with papillary cell renal cell carcinoma (PRCC), wherein aggressive and non-aggressive PRCC tumor types are characterized by differential expression profiles of genes that hybridize with one or more of these probes. Microarrays and kits for carrying out expression profiling of tumor tissue and methods of using them are disclosed.

Antibody specific for parafibromin, a new marker of parathyroid carcinoma

Abstract: Expression of the HRPT2 gene, which encodes parafibromin, is reduced in parathyroid carcinoma as well as in other carcinomas. Antibodies specific for parafibromin are disclosed, along with their use to evaluate levels of parafibromin in tissue samples. Loss of immunoreactivity is a highly selective marker for parathyroid carcinoma, and is a useful marker for kidney and bladder cancer, as well as other carcinomas, and provides the first laboratory test that can serve as a standard for pathological diagnosis of parathyroid cancer.