New determinates of disease progression and outcome in metastatic ovarian carcinoma
Ben Davidson1,2, Reuven Reich3, Claes G. Trope2,4, Tian-Li Wang5 and Ie-Ming Shih6
1Division of Pathology and 4Section of Gynecologic Oncology, Division of Gynecology and Obstetrics, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway, 2Faculty of Medicine, University of Oslo, Oslo, Norway, 3Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel, Departments of 5Gynecology and Oncology and 6Pathology, Johns Hopkins Medical Institutions, Baltimore MD, USA.
Offprint requests to: Ben Davidson, Division of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Montebello N-0310 Oslo, Norway. e-mail: firstname.lastname@example.org
Summary. Ovarian cancer is the most lethal gynecologic malignancy. This is attributed to frequent presentation at late stage, when the tumor has metastasized, as well as to development of chemotherapy resistance along tumor progression. Patients with advanced-stage ovarian carcinoma have widespread intraperitoneal metastases, including the formation of malignant serous effusions within the peritoneal cavity. Pleural effusions constitute the most frequent site of distant metastasis (FIGO stage IV disease). Unlike the majority of solid tumors, particularly at the primary site, cancer cells in effusions are not amenable to surgical removal, and failure in their eradication is one of the main causes of treatment failure. Our research in recent years has demonstrated that a large number of cancer-associated molecules are differentially expressed in effusions compared to primary carcinomas and solid metastases. We have additionally observed that expression of several of these molecules differs between primary diagnosis (pre-chemotherapy) and disease recurrence (post-chemotherapy) specimens, and that they are significantly associated with response to chemotherapy and patient survival. These observations are thought to be related to disease progression, as well as to the unique microenvironment of effusions, and may have impact on the selection of targeted therapy in this cancer. This review discusses our recent observations with respect to the biology of ovarian carcinoma cells in effusions, and focuses on the clinical role of tumor-associated molecules at this anatomic site. Histol Histopathol 25, 1591-1609 (2010)
Key words: Ovarian carcinoma, Effusion, Metastasis, Tumor progression, Chemotherapy, Prognosis