title: Tissue microarray analysis of EGFR and erbB2 copy number changes in ovarian tumors.
abstract: The objective of this study was to assess the implication of copy number changes of epidermal growth factor receptor (EGFR) and erbB2 genes in the etiology and progression of ovarian tumors. In our study, we used the highly reliable method of fluorescent in situ hybridization, applied on tissue microarray, containing 1006 ovarian tumors from different malignancy, histologic type and grade, and tumor stage, in order to analyze the correlations between gene copy number changes and tumor phenotype. We established copy number changes of erbB2 in 15.30% of malignant ovarian tumors-8.16% amplifications and 7.14% gains. The frequency of EGFR copy number changes was 10.67%-3.65% amplifications and 7.02% gains. EGFR gains occurred with approximately the same frequency in malignant (7.02%), low malignant potential (8.33%), and benign (7.19%) ovarian tumors. ErbB2 amplification was associated with clear cell type of ovarian cancer (P < 0.04). No amplification of EGFR and erbB2 genes was established in tumors with low malignant potency and in benign tumors. Regarding cancer phenotype, there was no statistically significant association between erbB2 copy number changes and histologic grade as well as tumor stage of ovarian cancer. EGFR gains are early events in ovarian tumorigenesis. Our results showed similar frequencies of EGFR gains in different grade tumors, while EGFR amplification increased from grades 1 to 2 to 3.
authors.affiliation: Department of Medical Genetics, Medical Faculty, Sofia, Bulgaria.
authors.forename: I
authors.initials: I
authors.lastname: Dimova
authors.forename: B
authors.initials: B
authors.lastname: Zaharieva
authors.forename: S
authors.initials: S
authors.lastname: Raitcheva
authors.forename: R
authors.initials: R
authors.lastname: Dimitrov
authors.forename: N
authors.initials: N
authors.lastname: Doganov
authors.forename: D
authors.initials: D
authors.lastname: Toncheva
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D010052:Ovariectomy; D011336:Probability; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis; D046509:Tissue Culture Techniques
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases