Die Rolle des prototypischen Kälteschockproteins Y-box Protein-1 im Magen-Adenokarzinom
OBJECTIVE: The aim of the retrospective study was to define the prognostic role of Y-box protein-1 in patients with gastric cancer.BACKGROUND: Despite improvements in the surgical treatment of gastric adenocarcinoma, recurrence rates remain high in patients with advanced disease. The overall 5-year survival rate of patients that underwent surgical R0-resection is 10-30%. The most important prognostic factors are lymph node involvement (N), metastasis (M), tumour stage (T) and the UICC-classification, although recent studies showed a discrepancy in the predictive value of these clinicopathologic factors in gastric cancer. The Y-box protein-1 belongs to the family of cold shock proteins that have pleiotropic functions such as gene-transcription, RNA splicing and mRNA translation. It regulates and interacts with many proteins such as p53, Notch-3, EGFR, PAI-1. The role of Y-box protein-1 has been widely investigated in various malignant tumours. It is highly expressed in cancers of the breast, prostate, ovary, lung, thyroid and bone. These findings suggest that Y-box protein-1 also plays a role in regulating the transcription and translation of genes contributing the transformation of gastric adenocarcinoma. METHODS: Tissue specimens of gastric carcinoma were obtained from 60 patients who underwent surgical R0-resection at the Department of Surgery, at the University Hospital Aachen between 1994 and 2002. The survival and recurrence rates of all patients were assessed prospectively until 2006. Monoclonal YB-1 antibody was used for immunostaining of paraffin sections. Protein expression was analyzed microscopically with the help of a score system according to Remmele et al.. Survival analyses were performed to evaluate the prognostic role of the clinical and histopathologic parameters and the correlations and co-expressions of clinicopathologic and histopathologic patterns were investigated.RESULTS: Y-box protein-1 was overexpressed in almost all cancerous lesions in comparison with normal gastric mucosa in surgically resected gastric carcinomas (p=0,0001). Cytoplasmatic expression of Y-box protein-1 correlated with Notch-3 (p=0,0004), Cox-2 (p=0,039) and HIF-1alpha (p=0,018) expression, whereas the expression of nuclear Y-box protein-1 correlated with tumour-grading (p=0,0034), Notch-3 (p=0,020) and uPAR (p=0,0001) expression. None of the parameters, neither the clinicopathologic, nor the histopathologic ones, showed an association to the survival rate of the cancer patients. There was no significant correlation between the co-expression of Y-box protein-1 with Notch-3, uPAR and Cox-2 and the patient outcome. CONCLUSIONS: Y-box protein-1 is highly overexpressed in gastric adenocarcinoma and seems to interact with several tumour-biological factors. The Y-box protein-1 appears not to be a prognostic marker in gastric cancer, neither in cytoplasmatic, nor in nuclear localisation. Further prospective studies are needed including taking samples of a greater number of patients verify our results.
info:eu-repo/classification/ddc/610, Magentumor, Kälteschock-Proteine, Tumormarker, Staging, Überleben, Medizin, YB-1, Prognosemarker, Proteinexpression, nucleäre Expression, Immunhistochemie, Y-box protein-1, gastric cancer, tumour staging, overexpression, prognostic parameter
Networked Digital Library of Theses and Dissertations
Publikationsserver der RWTH Aachen University