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Mutant Epidermal Growth Factor Receptor in Benign, Borderline, and Malignant Ovarian Tumors

Authors' Affiliations: Departments of ¹ Oncology, ² Pathology, and ³ Clinical Biochemistry, Vejle Hospital, Vejle, Denmark; ⁴ Department of Gynecology and Obstetrics, Horsens Hospital, Horsens, Denmark; ⁵ Institute of Human Genetics, University of Aarhus, Aarhus, Denmark; and ⁶ Institute for Regional Health Sciences, University of Southern Denmark, Odense, Denmark

Requests for reprints: Karina Dahl Steffensen, Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark. Phone: 45-79406833; Fax: 45-79406907; E-mail: Karina.Dahl.Steffensen{at}vgs.regionsyddanmark.dk.

Purpose: Dysfunction of the epidermal growth factor (EGF) complex is essential to the growth and development of many human tumors. Overexpression of the EGF receptor (EGFR) is a characteristic finding in a considerable number of solid tumors and often signalizes poor prognosis. There is a major disagreement among researchers about both the frequency and possible clinical importance of EGFR overexpression in ovarian cancer. The type III variant of EGFR (EGFRvIII) is a mutant with a deletion. Contrary to the wild-type, it is constitutively active. EGFRvIII has not been found in normal tissue, and consequently, it is an attractive tumor-specific candidate for molecular targeted treatment. The literature dealing with this mutation in ovarian cancer has been very sparse.

Experimental Design: Tissue from 225 patients who underwent surgery for a pelvic mass was collected consecutively. The samples included 99 ovarian/peritoneal/tuba cancers, 17 ovarian borderline tumors, 66 benign ovarian tumors, 15 other cancer types, 24 normal ovarian biopsies, and 4 miscellaneous. The presence of EGFRvIII was investigated both by PCR analyses for EGFRvIII gene expression and with protein analysis by Western blots.

Results: None of the tissue samples was positive for the EGFRvIII mutation neither at the mRNA level nor at the protein level.

Conclusions: The EGFRvIII mutation seems to be very rare in ovarian tissue. Our data indicate that EGFRvIII is not a part of the malignant phenotype in ovarian cancer and should not be pursued as a therapeutic target for treatment of this disease.