| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Human Pathology | ||||
| Publisher: | W B SAUNDERS CO-ELSEVIER INC | ||||
| Place of Publication: | PHILADELPHIA | ||||
| Volume: | 43 | ||||
| Number of Issue or Book Chapter: | 6 | ||||
| Page Range: | pp. 921-931 | ||||
| Date: | 2012 | ||||
| Institutions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Lehrstuhl für Hals-Nasen-Ohren-Heilkunde Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie Medicine > Lehrstuhl für Pathologie | ||||
| Identification Number: |
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| Keywords: | EPIDERMAL-GROWTH-FACTOR; IN-SITU HYBRIDIZATION; GENE COPY NUMBER; ADENOID CYSTIC CARCINOMA; SQUAMOUS-CELL CARCINOMAS; FACTOR RECEPTOR GENE; POOR-PROGNOSIS; BREAST-CANCER; COLORECTAL-CANCER; CYTOPLASMIC EXPRESSION; Salivary gland cancer; EGFR; HER2; Survivin; pSTAT3; Prognosis | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 63697 |
Web of ScienceAbstract
Increased gene copy number (high polysomy or amplification) of EGFR and HER2 has evolved as a predictor for response to targeted therapy. STAT3 and the apoptosis inhibitor survivin represent distinct oncogenes in various human neoplasms. The purpose of this study was to evaluate protein and gene status of these biomarkers by immunohistochemistry and dual color fluorescence in situ hybridization ...
Abstract
Increased gene copy number (high polysomy or amplification) of EGFR and HER2 has evolved as a predictor for response to targeted therapy. STAT3 and the apoptosis inhibitor survivin represent distinct oncogenes in various human neoplasms. The purpose of this study was to evaluate protein and gene status of these biomarkers by immunohistochemistry and dual color fluorescence in situ hybridization on tissue microarrays of 286 salivary gland carcinomas in the context of clinical and histopathologic characteristics. Diverse tumor types showed overexpression and increased gene copy number of EGFR and HER2. Amplification of HER2 was found in 35.5% of salivary duct carcinomas. Protein overexpression was strongly associated with high gene copy number for both EGFR and HER2 (P < .001). Overexpression and increased gene copy number of EGFR and HER2 were correlated to high-grade malignancy (P < .001) and unfavorable prognosis (P < .001). Strong nuclear staining of survivin was found in 18.9% of tumors and was associated with high-grade malignancy (P < .001), overexpression, and high gene copy number of EGFR and HER2 (P <= .05) as well as unfavorable prognosis (P < .001). Overexpression of nuclear pSTAT3 was found in 28.3% of tumors and correlated with well tumor differentiation (P < .001) and favorable prognosis (P = .001). Loss or weak expression of pSTAT3 was inversely associated with overexpression of survivin (P < .001) as well as overexpression and high gene copy number of EGFR and HER2 (P < .05). Overall, overexpression and increased gene copy number of EGFR and HER2 characterize high-grade malignancy with unfavorable prognosis in salivary gland cancer. Nuclear survivin typifies aggressive tumors with worse prognosis, whereas nuclear pSTAT3 might play a role as a tumor suppressor in absence of EGFR, HER2, and survivin. (c) 2012 Elsevier Inc. All rights reserved.
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