Identification of differentially expressed genes in clinically distinct groups of serous ovarian carcinomas using cDNA microarray.

To identify changes in gene expression in serous epithelial ovarian cancers (SEOC), we utilized cDNA microarrays consisting of 2382 genes with cancer related properties to analyze tumors from 20 patients with defined clinical out-comes. The significance analysis of microarrays method was used to determine differentially expressed genes, leading to the identification of 134 up-regulated and 231 down-regulated genes overall. By increasing the stringency of the statistical selection criteria, 41 over-expressed and 51 under-expressed genes were identified. The median duration of follow-up of the 20 patients was 16.8 months with a median progression free survival of 7.0 months. We found 11 genes that were differentially over-expressed in patients with recurrent disease, and 3 genes (homo sapiens mRNA for Ins P3 5-phophatase, lipoma HMGIC fusion partner-like 2 and CD63 melanoma 1 antigen) in patients who were dead of disease. Subsequently, we examined the distribution of the differentially expressed genes in the cDNA library database from adult human tumor and normal tissues using the DigiNorthern method to identify a subset of genes with relatively restricted tissue distribution. Finally, protein expression of 5 selected genes were further examined using immunohistochemistry applied on a tissue microarray prepared from an independent panel of 93 SEOC tissues. The results provided validation for 2 under-expressed genes (E2F transcription factor 5 and CK14) and 3 over-expressed genes (Bcl2-like 1, COX-2, CD63). Our study demonstrates differential gene expression in clinically distinct groups of SEOC using cDNA microarray. These genes may potentially be useful as biomarkers and/or targets for therapeutic intervention.

Prognostic significance of expression of p53 oncoprotein in primary (stage I-IIIa) non-small cell lung cancer.

Mutation of the p53 gene is one of the most common genetic abnormalities found in all types of human cancer. Accumulating evidence strongly indicates that p53 alterations play a role in tumorgenesis in non-small cell lung cancer (NSCLC). However, the role of p53 as a prognostic marker in NSCLC remains unclear. The data derived from the literature on prognostic impact of p53 in NSCLC has been a matter of controversy. Among the reasons for the discrepancy, are lack of correlation with key clinical parameters, patients with different stages, different antibodies used, and insufficient sample size. The intent of this study was to evaluate the prognostic value of p53 protein in a larger cohort of stage I-IIIa patients. Clinicopathological data was obtained on 179 patients with NSCLC. These data were correlated with the p53 status on the respective surgically resected tumors, using monoclonal antibody DO7. There is a significant relationship between strong p53 expression and patient survival. In a multivariate analysis, strong expression (> 50%) of the p53 oncoprotein is an independently favorable prognostic factor. Patients with strong p53 expression had a prolonged survival (p = 0.009, RR; 0.56, 95% CI: 0.35-0.86). The median time of survival for patients with strong and negative/weak p53 expression was more than 61 and 44 months, respectively. The present study suggests that p53 protein expression in tumor tissue may serve as a prognostic biomarker for NSCLC. This information may also potentially serve as a tool for clinical decision-making when selecting patients for adjuvant treatments of NSCLC.