Search

Your search keyword '"Girgis, Andrew H. A."' showing total 21 results
Start Over Author "Girgis, Andrew H. A."
21 results on '"Girgis, Andrew H. A."'

20. Lactate Dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma.

Author

Girgis, Hala, Masui, Olena, White, Nicole M. A., Scorilas, Andreas, Rotondo, Fabio, Seivwright, Annetta, Gabril, Manal, Filter, Emily R., Girgis, Andrew H. A., Bjarnason, Georg A., Jewett, Michael A. S., Evans, Andrew, Al-Haddad, Sahar, Siu, K. W. Michael, and Yousef, George M.

Subjects
RENAL cancer, RENAL cell carcinoma, LACTATE dehydrogenase, IMMUNOHISTOCHEMISTRY, CANCER invasiveness
Abstract

Background Over 90% of cancer-related deaths in clear cell renal cell carcinoma (RCC) are caused by tumor relapse and metastasis. Thus, there is an urgent need for new molecular markers that can potentiate the efficacy of the current clinical-based models of prognosis assessment. The objective of this study is to evaluate the potential significance of lactate dehydrogenase A (LDHA), assessed by immunohistochemical staining, as a prognostic marker in clear cell renal cell carcinoma in relation to clinicopathological features and clinical outcome. Methods We assessed the expression of LDHA at the protein level, by immunohistochemistry, and correlated its expression with multiple clinicopathological features including tumor size, clinical stage, histological grade, disease-free and overall survival in 385 patients with primary clear cell renal cell carcinoma. We also correlated the LDHA expression with overall survival, at mRNA level, in an independent data set of 170 clear cell renal cell carcinoma cases from The Cancer Genome Atlas databases. Cox proportional hazards models adjusted for the potential clinicopathological factors were used to test for associations between the LDHA expression and both disease-free survival and overall survival. Results There is statistically significant positive correlation between LDHA level of expression and tumor size, clinical stage and histological grade. Moreover, LDHA expression shows significantly inverse correlation with both disease-free survival and overall survival in patients with clear cell renal cell carcinoma. Our results are validated by examining LDHA expression, at the mRNA level, in the independent data set of clear cell renal cell carcinoma cases from The Cancer Genome Atlas databases which also shows that higher lactate dehydrogenase A expression is associated with significantly shorter overall survival. Conclusion Our results indicate that LDHA up-regulation can be a predictor of poor prognosis in clear cell renal cell carcinoma. Thus, it represents a potential prognostic biomarker that can boost the accuracy of other prognostic models in patients with clear cell renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Published
2014
Full Text
View/download PDF

21. The Chromatin Remodeling Gene ARID1AIs a New Prognostic Marker in Clear Cell Renal Cell Carcinoma

Author

Lichner, Zsuzsanna, Scorilas, Andreas, White, Nicole M.A., Girgis, Andrew H., Rotstein, Lora, Wiegand, Kimberly C., Latif, Ashraf, Chow, Christina, Huntsman, David, and Yousef, George M.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common tumor of the adult kidney, with an increasing rate of incidence. Recently, exome sequencing studies have revealed that the SWI/SNF (switch/sucrose nonfermentable) members PBRM1and ARID1Aare mutated in ccRCC, and it has also been suggested that aberrant chromatin regulation is a key step in kidney cancer pathogenesis. Herein, we show that down-regulation of another SW/SNF component, ARID1A, occurs frequently in ccRCC. We detected copy number loss of ARID1Ain 16% of patients with ccRCC. Immunohistochemistry indicated that 67% of ccRCC (53 of 79) had significantly lower expression of BAF250a, the protein product of ARID1A, than did the matched normal kidney cortex. In parallel, we conducted in silicomRNA expression analysis on 404 ccRCC tumors and 167 normal kidney cortex samples using publicly available databases and confirmed significant down-regulation of ARID1Ain 68.8% of patients. We also show that decreased BAF250a protein and ARID1AmRNA expression correlate with tumor stage and grade. Our results indicate that both the protein and mRNA levels of ARID1Aare statistically significant prognostic markers for ccRCC. Even after controlling for other confounders in the multivariate analysis, BAF250 retained its prognostic significance. BAF250a IHC is easy to perform and represents a potential biomarker that could be incorporated in laboratory practice to enhance the accuracy of the existing prognostic models.

Published
2013
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results