Search

High expression levels of EGFR mRNA are reported to be associated with a higher response probability in epidermal growth factor receptor (EGFR) targeted drugs. Our aim was to determine how EGFR gene expression levels in primary colorectal cancer (CRC) were related to those in liver metastases. 31 pairs of primary CRC and corresponding liver metastases were analyzed. Gene expression level was measured using real-time RT-PCR. No significant difference was observed between median mRNA expression levels of EGFR in primary cancer and those in corresponding liver metastases ( P = 0.99). When matched tissue sets were compared on an individual basis, there was a significant correlation for EGFR mRNA expression between primary cancer and corresponding liver metastases ( rs = 0.78, P < 0.0001). A good prediction of EGFR mRNA levels in liver metastases can be obtained by measuring those in the primary CRC. [ABSTRACT FROM AUTHOR]

In order to identify genes or combination of genes that have the power to discriminate between premalignant Barrett's esophagus and Barrett's associated adenocarcinoma, we analysed a panel of 23 genes using quantitative real-time RT-PCR (qRT-PCR, Taqman®) and bioinformatic tools. The genes chosen were either known to be associated with Barrett's carcinogenesis or were filtered from a previous cDNA microarray study on Barrett's adenocarcinoma. A total of 98 tissues, obtained from 19 patients with Barrett's esophagus (BE group) and 20 patients with Barrett's associated esophageal adenocarcinoma (EA group), were studied. Triplicate analysis for the full 23 gene of interest panel, and analysis of an internal control gene, was performed for all samples, for a total of more than 9016 single PCR reactions. We found distinct classes of gene expression patterns in the different types of tissues. The most informative genes clustered in six different classes and had significantly different expression levels in Barrett's esophagus tissues compared to adenocarcinoma tissues. Linear discriminant analysis (LDA) distinguished four genetically different groups. The normal squamous esophagus tissues from patients with BE or EA were not distinguishable from one another, but Barrett's esophagus tissues could be distinguished from adenocarcinoma tissues. Using the most informative genes, obtained from a logistic regression analysis, we were able to completely distinguish between benign Barrett's and Barrett's adenocarcinomas. This study provides the first non-array parallel mRNA quantitation analysis of a panel of genes in the Barrett's esophagus model of multistage carcinogenesis. Our results suggest that mRNA expression quantitation of a panel of genes can discriminate between premalignant and malignant Barrett's disease. Logistic regression and LDAs can be used to further identify, from the complete panel, gene subsets with the power to make these diagnostic distinctions. Expression analysis of a limited number of highly selected genes may have clinical usefulness for the treatment of patients with this disease.Oncogene (2004) 23, 4780-4788. doi:10.1038/sj.onc.1207663 Published online 26 April 2004 [ABSTRACT FROM AUTHOR]

The Barrett''s multistage process is characterized histopathologically by progression from Barrett''s intestinal metaplasia to Barrett''s esophagus with dysplasia and ultimately adenocarcinoma. Understanding of the molecular alterations in this multistage process may contribute to improved diagnosis and treatment. Retinoid X receptors (RXR) play an important role in regulating the morphogenesis, development, growth, and differentiation of cells. Alterations in RXR expression have been observed in a variety of solid tumors; however, the role in Barrett''s esophagus disease has yet to be determined. The aim of this study was to assess the prevalence and timing of RXR messenger RNA expression in the Barrett''s metaplasia-dysplasia-adenocarcinoma sequence and to investigate its role in the development and progression of this disease. We analyzed the mRNA expression of all three RXR subtypes (RXR-alpha, RXR-beta, and RXR-gamma) by using a quantitative real-time reverse transcription–polymerase chain reaction method in 108 specimens from 19 patients with Barrett''s esophagus without carcinoma (BE group), 20 patients with Barrett''s-associated adenocarcinoma (EA group), and a control group of 10 patients without evidence of gastroesophageal reflux disease (CG). RXR-α mRNA expression was significantly decreased (P < 0.001; Kruskal-Wallis test), and RXR-γ was significantly increased (P < 0.001) at higher stages in Barrett''s esophagus. RXR-β expression was highest in Barrett''s tissues and was significantly increased compared to normal squamous tissues (P = 0.01; Wilcoxon test) and adenocarinoma tissues (P = 0.018, Mann-Whitney test). RXR-α and RXR-β mRNA expression was significantly associated in normal squamous esophagus tissues (r2 = 0.49; P < 0.001; Spearman test), Barrett''s tissues (r2 = 0.63; P < 0.001), and adenocarcinoma tissues (r2 = 0.68; P = 0.001). There were significant differences in RXR-α (P = 0.011) and RXR-β (P = 0.005) mRNA expression in histopathologically normal squamous esophagus tissues in patients with cancer and the control group without evidence of gastroesophageal reflux disease. These findings suggest that alterations in the mRNA expression of all three RXR subtypes are frequent events in the development and progression of Barrett''s esophagus and associated adenocarcinoma, that RXR mRNA expression levels may be useful biomarkers for this disease, and that a widespread “field-effect” is present in the normal esophagus of patients with esophageal adenocarcinoma. [Copyright &y& Elsevier]

These studies investigated the role of cyclooxygenase gene expression in esophageal diseases. The study from Germany by Zimmerman et al. detected cytoplasmic cyclooxygenase- 2 (COX-2) protein expression by immunohistochemistry in 156 of 172 (91%) esophageal squamous cell carcinomas (SCC) and in 21 of 27 (78%) Barrett's-associated esophageal adenocarcinomas. There was a wide range in COX-2 immunoreactivity in different cancer specimens, and also within individual specimens. Western blot analysis of COX-2 protein levels was performed for some of the SCC samples, confirming the immunohistochemistry results. No COX-2 protein expression was detected immunohistochemically in Barrett's intestinal metaplasia tissues. There were no significant associations between COX immunoreactivity and tumor stage for either cancer type, except for a higher frequency of local lymph node metastases in SCC patients with low COX-2 expression. In vitro studies using SCC cell lines showed that expression of COX-2 at the mRNA level was associated with production of both COX-2 protein and high prostaglandin (PGE2 and 6-keto-PGFlα) levels. Finally, this study showed that treatment of the COX-2-expressing SCC cells with the COX inhibitors flusolide and NS-398 inhibited prostaglandin synthesis, suppressed proliferative and mitotic activity, and induced widespread apoptosis (the apoptotic effect was assessed with flusolide only). In the non-COX- 2-expressing cell line, none of these effects were observed. The earlier publication, by Wilson et al., from the University of Maryland School of Medicine, used a reverse transcriptase-polymerase chain reaction method to detect elevated COX-2 mRNA levels in 15 of 19 (79%) Barrett's intestinal metaplasia specimens, 2 of 2 (100%) Barrett's dysplasia specimens, and 5 of 5 (100%) Barrett's-associated adenocarcinomas. Increased levels of COX-2 protein, inducible nitric oxide synthase mRNA, and transforming growth factor-α mRNA were also present in similar proportions in Barrett's esophagus and adenocarcinoma tissues. [ABSTRACT FROM AUTHOR]

Abstract: Background: The effect of the apoptosis related gene Bcl-2 in the pathogenesis in NSCLC remains poorly investigated. Hence the aim of this study was to explore the potential role of Bcl-2 mRNA expression as a prognostic biomarker in patients with curatively resected NSCLC. Methods: 91 tumor and matching normal tissue samples from patients with NSCLC were analyzed using a quantitative real-time RT-PCR method. The relative Bcl-2 mRNA expression was measured using β-actin as a reference gene. 45 of the 91 patients had stage I tumors (49%), 19 had stage II (21%) and 27 had stage IIIa (30%). Squamous cell carcinoma was found in 43 patients (47%), adenocarcinoma in 33 (36%) and in large cell carcinoma in 15 (17%) of the patients. Results: Bcl-2 mRNA expression was detected in 83 (91%) of the investigated tumor samples and in 74 (81%) of the normal lung tissue. The median gene expression was 0.147 in tumor tissue and 0.144 in matching normal lung tissue (p =n.s., Wilcoxon Test). No associations were seen between the tumorous Bcl-2 mRNA expression levels and clinical or histopathologic parameters such as gender, tumor size, TNM stadium and grading, but with tumor histology and smoking. With a follow-up of 85.9 months, the median survival time was 59.7 months. Bcl-2 mRNA expression was significantly associated with patients prognosis (p =0.013, log-rank test). Multivariate regression analysis revealed Bcl-2 expression status and tumor stage as independent prognostic factor. Conclusions: Bcl-2 expression in NSCLC is not associated with the pathogenesis of this disease. Our data suggests that Bcl-2 mRNA expression plays a crucial role in the biological behavior of NSCLCs. Quantitation of Bcl-2 expression improves estimation of prognosis and appears to identify patients who will benefit from intensive adjuvant therapy. [ABSTRACT FROM AUTHOR]