Biomedical subjects

Yunda Huang

Publications and source records attributed to Yunda Huang.

7 recordsLinked to original sources

PubMed2004

Epithelial cell adhesion molecule (KSA) expression: pathobiology and its role as an independent predictor of survival in renal cell carcinoma.

PURPOSE: Epithelial cell adhesion molecule (EpCAM) is a widely expressed adhesion molecule in epithelial cancers. The purpose of this study is to determine the protein expression patterns of EpCAM in renal cell carcinoma (RCC) using tissue arrays linked to a clinicopathological database to evaluate both its predictive power in patient stratification and its suitability as a potential target for immunotherapeutic treatment strategies. EXPERIMENTAL DESIGN: The University of California, Los Angeles kidney cancer tissue microarray contains specimens from 417 patients treated with nephrectomy. EpCAM protein expression in tumors and matched morphologically normal renal tissues was evaluated using anti-EpCAM immunohistochemistry. The resultant expression reactivity was correlated with clinicopathological variables. RESULTS: EpCAM is consistently expressed in the distal nephron on normal renal epithelium. Clear cell RCCs show minimal and infrequent EpCAM expression, whereas chromophobe and collecting duct RCCs both demonstrate intense and frequent expression. Of 318 clear cell carcinomas used in the analysis, 10% were EpCAM positive in > or = 50% of cells, and 8% of patients would be considered candidates for EpCAM-based therapy, based on high expression [> or = moderate intensity and frequent (> or = 50%) expression] and the need for systemic treatment. EpCAM expression was an independent prognostic factor for improved disease-specific survival, with a multivariate hazard ratio of 0.63 (P = 0.017; 95% confidence interval, 0.43-0.92). CONCLUSIONS: EpCAM is a novel prognostic molecular marker in RCC patients, and its positive expression is an independent predictor associated with improved survival. However, high expression in morphologically normal renal tissues and minimal or absent expression in clear cell carcinomas will likely limit the utility of this epithelial marker in targeted treatments of this most common RCC type.

Adenocarcinoma, Clear Cell↗

PubMed2004

Statistical methods for analyzing tissue microarray data.

Tissue microarrays (TMAs) are a new high-throughput tool for the study of protein expression patterns in tissues and are increasingly used to evaluate the diagnostic and prognostic importance of biomarkers. TMA data are rather challenging to analyze. Covariates are highly skewed, non-normal, and may be highly correlated. We present statistical methods for relating TMA data to censored time-to-event data. We review methods for evaluating the predictive power of Cox regression models and show how to test whether biomarker data contain predictive information above and beyond standard pathology covariates. We use nonparametric bootstrap methods to validate model fitting indices such as the concordance index. We also present data mining methods for characterizing high risk patients with simple biomarker rules. Since researchers in the TMA community routinely dichotomize biomarker expression values, survival trees are a natural choice. We also use bump hunting (patient rule induction method), which we adapt to the use with survival data. The proposed methods are applied to a kidney cancer tissue microarray data set.

Algorithms↗

PubMed2004

Prognostic value of carbonic anhydrase IX and KI67 as predictors of survival for renal clear cell carcinoma.

PURPOSE: The natural history of renal cell carcinoma (RCC) is complex and not entirely explained by conventional prognostic factors. In this study we evaluated the prognostic value of carbonic anhydrase IX (CAIX) and Ki67 to predict survival in RCC. MATERIALS AND METHODS: Immunohistochemical analysis using a CAIX and a Ki67 monoclonal antibody was performed on tissue microarrays constructed from paraffin embedded specimens from 224 patients treated with nephrectomy for clear cell renal carcinoma. CAIX and Ki67 staining were correlated with clinical factors, pathological features and survival. Median followup was 34 months (range 0.3 to 117) and disease specific survival was the primary end point assessed. RESULTS: Univariate statistical analysis showed that high Ki67 staining and low CAIX staining correlated significantly with poor median survival (21 months, p < 0.001 and 22 months, p = 0.011, respectively). Each marker was highly significant for stratifying patient groups defined by T stage, Fuhrman grade, nodal status, metastatic status and performance status. On multivariate analysis CAIX and Ki67 were significant predictors of survival with an HR of 1.78 (p = 0.014) and 1.75 (p = 0.009), respectively. Although CAIX and Ki67 staining were inversely correlated (p = 0.009), Ki67 significantly substratified patient subgroups defined by high or low CAIX staining (p = 0.001 and 0.003, respectively). When Ki67 and CAIX were combined into a single parameter, RCC tumors could be stratified into low, intermediate and high risk groups with a median survival of greater than 101, 31 and 9 months, respectively (p <0.001). On multivariate analysis the combined parameter consisting of Ki67 and CAIX was a significant predictor of survival (p <0.001) and it was able to displace histological grade. CONCLUSIONS: Ki67and CAIX are useful prognostic biomarkers for RCC that improve the survival prediction and classification of kidney cancer.

Adult↗

PubMed2003

Analysis of the Na,K-ATPase alpha- and beta-subunit expression profiles of bladder cancer using tissue microarrays.

BACKGROUND: The purpose of this study was to determine the clinical significance of Na,K-ATPase alpha- and beta-subunit expression in a histopathologically well-characterized group of patients representing a wide spectrum of tumor grades and disease stages with transitional cell carcinomas (TCC). METHODS: Na,K-ATPase alpha- and beta-subunit protein expression patterns were analyzed using immunohistochemistry on urothelial cancer tissue microarrays (TMA) of 146 patients diagnosed with urothelial carcinoma. For each subunit, the maximum staining intensity and the percentage of positive cells staining at the maximal intensity were analyzed. RESULTS: Compared with the benign fields, the mean protein expression for both Na,K-ATPase alpha- and beta-subunits were found to be decreased overall in in situ and invasive tumors, as well as in tumor-adjacent dysplastic fields. When Na,K-ATPase alpha- and beta-subunit expression levels were dichotomized into distinct groups, they were both found to be significant predictors of recurrence risk in multivariate logistic regression analysis (P = 0.0062, odds ratio [OR] = 2.6 and P = 0.013, OR = 0.43, for Na,K-ATPase alpha- and beta-subunits, respectively). The authors also found that patients with high alpha- and low beta-subunit expression had a high risk for early recurrence, whereas patients with a low alpha- and high beta-subunit expression had a significantly longer median recurrence-free time (17 months and 125 months, respectively, log rank statistics P = 0.0005). CONCLUSIONS: The results suggested that Na,K-ATPase alpha- and beta-subunit expression levels may be useful predictors of clinical outcomes such as recurrence-free time of bladder cancer patients.

Adult↗

PubMed2003

Correlation of Ki-67 and gelsolin expression to clinical outcome in renal clear cell carcinoma.

OBJECTIVES: To analyze the expression levels of Ki-67 and gelsolin in renal cell carcinoma (RCC) and determine their prognostic value in association with other clinicopathologic factors using tissue microarray technology. Histologic nuclear grade, performance status, and clinical stage are important prognostic factors in RCC. Because patients with tumors of similar grade, performance status, and stage may show a wide variation in biologic behavior and clinical outcome, additional biomarkers for RCC are needed to provide further prognostic information and possibly offer insight into the mechanisms of the disease. METHODS: Using a renal cancer tissue microarray, we correlated the expression of Ki-67, a marker of cell proliferation, and gelsolin, an actin-binding protein, with grade, stage, and survival in patients with clear cell RCC. RESULTS: In Cox multivariate regression analysis, stage (pT) was the most significant predictor of cancer-specific survival (P <0.0001), followed by Ki-67 (P = 0.0216). In univariate analysis, increased Ki-67 expression predicted poor cancer-specific survival (P = 0.0006) when a cutoff value for Ki-67 staining was applied. In patients with grade 2 tumors, increased Ki-67 expression and decreased gelsolin expression in the same tumor was suggestive of poor cancer-specific survival (P = 0.0507). CONCLUSIONS: Our findings support the utility of Ki-67 as a prognostic biomarker for RCC and suggest a role for gelsolin in renal carcinogenesis.

Adenocarcinoma, Clear Cell↗

PubMed2003

Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy.

PURPOSE: Metastatic renal cell carcinoma (RCC) has a poor prognosis and an unpredictable course. To date, there are no molecular markers which can reliably predict RCC outcome. We investigated whether a novel kidney cancer marker, carbonic anhydrase IX (CAIX), is associated with progression and survival. EXPERIMENTAL DESIGN: Immunohistochemical analysis using a CAIX monoclonal antibody was performed on tissue microarrays constructed from paraffin-embedded specimens from patients (N = 321) treated by nephrectomy for clear cell RCC. CAIX staining was correlated with response to treatment, clinical factors, pathologic features, and survival. RESULTS: CAIX staining was present in 94% of clear cell RCCs. Survival tree analysis determined that a cutoff of 85% CAIX staining provided the most accurate prediction of survival. Low CAIX (</=85%) staining was an independent poor prognostic factor for survival for patients with metastatic RCC, with a hazard ratio of 3.10 (P < 0.001). CAIX significantly substratified patients with metastatic disease when analyzed by T stage, Fuhrman grade, nodal involvement, and performance status (P < 0.001, = 0.001, = 0.009, = 0.005, respectively). For patients with nonmetastatic RCC and at high risk for progression, low CAIX predicted a worse outcome similar to patients with metastatic disease (P = 0.058). Overall expression of CAIX decreased with development of metastasis; as demonstrated by the lower CAIX staining levels in metastatic lesions relative to matched primary tumor specimens (P = 0.036). CONCLUSIONS: On the basis of our data, CAIX is the most significant molecular marker described in kidney cancer to date. Decreased CAIX levels are independently associated with poor survival in advanced RCC. CAIX reflects significant changes in tumor biology, which should be used to predict clinical outcome and identify high-risk patients in need for adjuvant immunotherapy and CAIX-targeted therapies.

Adenocarcinoma, Clear Cell↗

PubMed2002

Ki67, gelsolin and PTEN expression in sarcomatoid renal tumors.

Sarcomatoid renal tumors differ morphologically and prognostically from other renal tumors. Using tissue microarray technology, we show that sarcomatoid renal tumors have a distinct protein expression profile for biomarkers Ki67, gelsolin and PTEN, when compared with clear-cell and papillary renal tumors. Our results confirm the previous reports that Ki67 is highly expressed in sarcomatoid tumors. We also show that gelsolin expression differs between the studied tumor types, suggesting different roles for gelsolin in the carcinogenesis of different renal tumor types.

Carcinoma, Papillary↗