| Item type: | Article | ||||||||||||||||||||||||||||||||||||||
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| Journal or Publication Title: | Human pathology | ||||||||||||||||||||||||||||||||||||||
| Publisher: | W B SAUNDERS CO-ELSEVIER INC | ||||||||||||||||||||||||||||||||||||||
| Place of Publication: | PHILADELPHIA | ||||||||||||||||||||||||||||||||||||||
| Volume: | 39 | ||||||||||||||||||||||||||||||||||||||
| Number of Issue or Book Chapter: | 1 | ||||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 126-136 | ||||||||||||||||||||||||||||||||||||||
| Date: | 2008 | ||||||||||||||||||||||||||||||||||||||
| Institutions: | Medicine > Abteilung für Thoraxchirurgie Medicine > Lehrstuhl für Pathologie Medicine > Lehrstuhl für Urologie | ||||||||||||||||||||||||||||||||||||||
| Identification Number: |
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| Classification: |
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| Keywords: | GENE-EXPRESSION; BETA-CATENIN; BRONCHIAL EPITHELIUM; E-CADHERIN; CIGARETTE-SMOKING; BLADDER-CANCER; P53 MUTATIONS; TUMOR-CELLS; ADENOCARCINOMA; CARCINOMAS; lung cancer; prognosis; immunohistochemistry | ||||||||||||||||||||||||||||||||||||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||||||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||||||||
| Refereed: | Unknown | ||||||||||||||||||||||||||||||||||||||
| Created at the University of Regensburg: | Unknown | ||||||||||||||||||||||||||||||||||||||
| Item ID: | 15516 |
Web of ScienceAbstract
Comprehensive expression analysis using microarrays has identified a number of differentially expressed genes in smoke-exposed bronchial epithelium and non-small cell lung cancers (NSCLCs). To evaluate the prognostic relevance of these proteins in NSCLCs, we used immunohistochemistry to investigate the expression of beta-catenin (CTNNB1), dickkopf, Xenopus, homolog of 3 (DKK3 gene), fibroblast ...
Abstract
Comprehensive expression analysis using microarrays has identified a number of differentially expressed genes in smoke-exposed bronchial epithelium and non-small cell lung cancers (NSCLCs). To evaluate the prognostic relevance of these proteins in NSCLCs, we used immunohistochemistry to investigate the expression of beta-catenin (CTNNB1), dickkopf, Xenopus, homolog of 3 (DKK3 gene), fibroblast growth factor receptor 3 (FGFR3), fragile histidine triad (FHIT), tumor protein p53 (TP53), mucinl (MUC1), topoisomerase II alpha (TOP2A), and glutathione Stransferase-Pi (GST) in a cohort of patients (n = 125). We correlated the expression data with clinicopathologic features and clinical outcome. In addition, SNaPshot multiplex assays (Applied Biosystems, Darmstadt, Germany) and restriction fragment length polymorphism analysis were used to screen for activating point mutations at the hot spots of FGFR3 in a cohort of 30 samples of NSCLC. Using Kaplan-Meier analysis, we observed significantly better overall survival in adenocarcinomas compared with squamous cell cancers (P = .049). Loss of FHIT expression showed a strong association with shorter overall survival in both histologic types of NSCLC (squamous cell cancers, P < .001; adenocarcinomas, P = .001). In adenocarcinomas, the cytoplasmic expression of beta-catenin was associated with shorter survival (P = .012); MUC1 expression was associated with worse prognosis in patients with squamous cell cancers (P = .002). The nuclear staining of TP53 (P = .008) and TOP2A (P = .059) was associated with cancers without lymphonodal metastases. A correlation with positive staining of TOP2A (P = .03) and FGFR3 positivity (P = .057) was found in adenocarcinomas of male patients. Positive MUC1 stainings were associated with squamous cell cancers of male patients (P = .03). DKK3 expression did not show any significant association with clinical outcome or pathologic features. The screening of the FGFR3 sequence in lung cancers showed only wild-type sequences and did not detect mutations in the known hot spots for FGFR3 mutations. We conclude that the immunohistochemical loss of FHIT expression and the positivity for beta-catenin and MUC1 in NSCLC are useful prognostic markers, whereas the variable expression of TP53, TOP2A, and FGFR3 in relation to the different histologic types of NSCLC and sex of the patients is suggestive for different underlying molecular pathways. (c) 2008 Elsevier Inc. All rights reserved.
Metadata last modified: 29 Sep 2021 07:37
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