Abstract
BackgroundLimited effectiveness of therapeutic agents targeting epidermal growth factor receptor (EGFR) in clinical trials using unselected ovarian cancer patients has prompted efforts to more effectively stratify patients who might best benefit from these therapies. A series of studies that have evaluated immunohistochemical (IHC) staining of EGFR in ovarian cancer biopsies has produced unclear results as to the utility of this measure as a prognostic biomarker. Here, we used one of the largest, single institution cohorts to date to determine possible associations of EGFR expression with patient outcome.MethodsWe performed IHC staining of EGFR in tissue microarrays including nearly 500 patient tumor samples. Staining was classified by subcellular localization (membranous, cytoplasmic) or by automated image analysis algorithms. We also performed a literature review to place these results in the context of previous studies.ResultsNo significant associations were found between EGFR subcellular localization or expression and histology, stage, grade, or outcome. These results were broadly consistent with the consensus of the reviewed literature.ConclusionsThese results suggest that IHC staining for EGFR may not be a useful prognostic biomarker for ovarian cancer patients. Future studies should pursue other staining methods or analysis in combination with other pathway mediators.
Highlights
IntroductionWith only a 45% 5-year survival rate, remains one of the most devastating malignancies for women [1]
Ovarian cancer, with only a 45% 5-year survival rate, remains one of the most devastating malignancies for women [1]
Selective Epidermal growth factor receptor (EGFR) inhibitors have been recommended as first-line therapy in lung cancer patients harboring EGFR mutations [3,4,5], and have shown modest effectiveness against tumors of the pancreas [6, 7] Identification that EGFR is expressed in up to 90% of certain histotypes of ovarian tumors led to investigation of this molecule as a potential prognostic www.impactjournals.com/Genes&Cancer biomarker as well as therapeutic target in ovarian cancer [8, 9]
Summary
With only a 45% 5-year survival rate, remains one of the most devastating malignancies for women [1]. Selective EGFR inhibitors have been recommended as first-line therapy in lung cancer patients harboring EGFR mutations [3,4,5], and have shown modest effectiveness against tumors of the pancreas [6, 7] Identification that EGFR is expressed in up to 90% of certain histotypes of ovarian tumors led to investigation of this molecule as a potential prognostic www.impactjournals.com/Genes&Cancer biomarker as well as therapeutic target in ovarian cancer [8, 9]. Limited effectiveness of therapeutic agents targeting epidermal growth factor receptor (EGFR) in clinical trials using unselected ovarian cancer patients has prompted efforts to more effectively stratify patients who might best benefit from these therapies. We used one of the largest, single institution cohorts to date to determine possible associations of EGFR expression with patient outcome
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