title: Gene expression profiles in three histologic types, clear-cell, endometrioid and serous ovarian carcinomas.
abstract: Ovarian carcinoma is the most lethal type of gynecologic malignancy in the Western world. Majority of early stage ovarian cancers are asymptomatic and this is the main reason that more than two-thirds of patients are diagnosed with advanced disease. Ovarian tumors are heterogeneous and the different histologic subtypes are further classified as benign, borderline (low-grade) and malignant (high-grade) to reflect their behavior. The aim of the study was to analyze gene expression profiles in three histologic types of ovarian carcinoma in an attempt to find the molecular differences among serous, endometrioid and clear cell subtypes. The analysis of gene expression was performed on 57 samples of ovarian carcinoma. RNA was isolated from the ovarian cancer tissues. The gene expression changes were determined by microarray analysis and quantitative real time polymerase chain reaction (qRT-PCR). Measurement of relative gene expression levels was used to identify molecular differences among three histologic types of ovarian carcinoma (clear-cell, endometrioid and serous). Unsupervised statistical analysis revealed four biological subtypes among three histotypes under study. The endometrioid ovarian carcinoma was divided into two molecular subtypes. The biggest molecular differences were observed between clear-cell and serous carcinomas (1070 genes, FDR 0.05), the smallest between endometrioid and serous carcinomas (81 genes, FDR 0.05). The biggest group of differentially expressed genes was involved in transport and metabolism. This finding can explain the differences in the response to chemotherapy observed among different histologic types of ovarian carcinomas. In conclusion, we found TCF2 (HNF1B) gene as a suitable marker for ovarian clear cell carcinoma. Gene expression profiling also shed light on the molecular mechanisms of different chemoresistance among the analyzed histotypes.
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Pamuła-Piłat
authors.affiliation: Institute of Radioelectronics, Warsaw University of Technology, Warsaw, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Rubel
authors.affiliation: Department of Molecular Pathology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: I K
authors.initials: IK
authors.lastname: Rzepecka
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Olbryt
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Herok
authors.affiliation: Department of Molecular Pathology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Dansonka-Mieszkowska
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Grzybowska
authors.affiliation: Department of Molecular Pathology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Kupryjańczyk
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics*; D018269:Carcinoma, Endometrioid / Q000235:genetics*; D002465:Cell Movement; D018284:Cystadenocarcinoma, Serous / Q000235:genetics*; D005260:Female; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta