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.
Subject(s)
ErbB Receptors/metabolism , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Receptor, ErbB-2/metabolism , Tissue Array Analysis , Adult , Aged , Biomarkers, Tumor/analysis , ErbB Receptors/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , In Situ Hybridization , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/surgery , Ovariectomy , Probability , Receptor, ErbB-2/genetics , Risk Assessment , Sampling Studies , Sensitivity and Specificity , Tissue Culture TechniquesABSTRACT
The objective of this study was to investigate increases in c-myc gene copy-number in ovarian tumours, and to analyze their correlations with clinicopathological parameters. Here we applied FISH on TMA (tissue microarrays) containing 507 ovarian tumour samples from different malignancy, histology, stage and grade. Overall, we found high frequency for c-myc copy-number increases (38.5%) in ovarian cancers: 22.1% amplifications and 16.4% gains. We established c-myc amplification in more than 30% in endometrioid and mixed epithelial ovarian carcinomas. c-myc gains were found in a high proportion (42.9%) of clear cell carcinomas. We found associations between c-myc copy-number changes and clinicopathological parameters of ovarian tumours such as degree of malignancy and histological type. We suggested that c-myc amplifications are characteristics for endometrioid, and c-myc gains for clear cell ovarian cancers. We suggest that copy-number increases of c-myc and 20q13.2 represent a possible mechanism for the regulation of the pathway STK15--c-myc--hTERT.
Subject(s)
Gene Amplification , Gene Dosage/genetics , Genes, myc/genetics , Ovarian Neoplasms/genetics , Aurora Kinase A , Aurora Kinases , DNA-Binding Proteins/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Ovarian Neoplasms/pathology , Phenotype , Protein Serine-Threonine Kinases/genetics , Telomerase/geneticsABSTRACT
Overrepresentations in 20q have been reported in a number of ovarian cancers by comparative genomic hybridization. In order to study the relation of the increased copy number of 20q13.2 with tumor phenotype in ovarian cancer, we applied FISH on a tissue microarray. The TMA technology enables us to analyze a large number of different malignancy, histology, stage and grade tumors. Overall, the frequency of 20q13.2 alterations in epithelial ovarian cancer was 25.50% (10.74% gains and 14.76% amplifications). There was not statistically significant difference between the frequencies of 20q13.2 copy number changes in different grade tumors. The frequency of gains and amplifications increased significantly from stage I to stage II to stage III tumors. Our results showed strong association between increases 20q13.2 copies and advanced tumor stage. We concluded that genetic alterations in 20q13.2 may be of prognostic significance for stage progression of the ovarian cancer.
