Claudin-4, mitogen-activated protein kinase kinase 4, and stratifin are markers of gastric adenocarcinoma precursor lesions
| Autor: | Keith D. Lillemoe, Michael A. Choti, Steven C. Cunningham, Min P. Kim, Charles J. Yeo, Richard E. Heitmiller, John L. Cameron, Raqeeb Haque, Sommer Hammoud, Elizabeth A. Montgomery, Richard D. Schulick, Anirban Maitra, Steven R. Hustinx, Raheela Ashfaq, Christine A. Iacobuzio-Donahue, Farin Kamangar |
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| Rok vydání: | 2006 |
| Předmět: |
Exonucleases
Male Epithelial dysplasia Pathology medicine.medical_specialty Epidemiology MAP Kinase Kinase 4 Gene Expression Adenocarcinoma Stomach Neoplasms medicine Biomarkers Tumor Humans Mesothelin Claudin-4 Stomach cancer Fascin Aged Metaplasia Tissue microarray biology Intestinal metaplasia Cancer Membrane Proteins medicine.disease Microarray Analysis Immunohistochemistry digestive system diseases Neoplasm Proteins Oncology 14-3-3 Proteins Tissue Array Analysis Exoribonucleases biology.protein Female Precancerous Conditions |
| Zdroj: | Cancer epidemiology, biomarkersprevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 15(2) |
| ISSN: | 1055-9965 |
| Popis: | Approximately 23,000 new gastric cancer cases and 12,000 associated deaths occur annually in the United States. Intestinal metaplasia and gastric epithelial dysplasia are precursor lesions to gastric adenocarcinoma, but are not readily detectable clinically, radiographically, or endoscopically. A noninvasive method of precursor detection would require the ability to distinguish precursor lesions from adjacent normal mucosa. In search of such markers, tissue microarrays were prepared for 133 patients of resected gastric adenocarcinoma. Tissue microarrays contained primary cancer, normal stomach, intestinal metaplasia, and gastric epithelial dysplasia and were probed with antibodies against nine potential markers that were either identified in a database of genes overexpressed in gastric adenocarcinoma or were already of interest to our laboratory: claudin-4, mitogen-activated protein kinase kinase 4 (MKK4), 14-3-3σ (stratifin), S100A4, mesothelin, fascin, topoisomerase IIα, HER-2/neu, and epithelial growth factor receptor. Three markers discriminated gastric adenocarcinoma precursor lesions from normal gastric mucosa. Claudin-4 expression was present in 36 intestinal metaplasia lesions (100%) and 14 gastric epithelial dysplasia lesions (100%), but in only 16 normal stomach samples (15%). MKK4 expression was present in 24 intestinal metaplasia lesions (89%) and 12 gastric epithelial dysplasia lesions (100%), but in only 6 normal stomach samples (8%). Stratifin expression was present in 29 intestinal metaplasia lesions (97%) and 8 gastric epithelial dysplasia lesions (100%), but in only 2 normal stomach samples (3%). Sensitivity and specificity for detection of the precursor lesion intestinal metaplasia were 100% and 85%, respectively, for claudin-4; 89% and 92%, respectively, for MKK4; and 97% and 97%, respectively, for stratifin. In primary cancers, 123 of 125 (98.4%) were positive for claudin-4, 116 of 126 (94%) for MKK4, and 111 of 120 (92%) for stratifin. In conclusion, claudin-4, MKK4, and stratifin immunolabeling detects precursor lesions of gastric adenocarcinoma that are otherwise clinically, radiographically, and endoscopically inapparent. These findings may prove useful in the diagnosis and therapeutic targeting of gastric adenocarcinoma precursor lesions. (Cancer Epidemiol Biomarkers Prev 2006;15(2):281–7) |
| Databáze: | OpenAIRE |
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