Disease Markers - Volume 23, issue 5-6

Authors: Birrer, M.

Article Type: Other

Citation: Disease Markers, vol. 23, no. 5-6, pp. 353-353, 2007

Authors: Pinheiro, Simone P. | Cramer, Daniel W.

Article Type: Research Article

Citation: Disease Markers, vol. 23, no. 5-6, pp. 355-366, 2007

Authors: Mok, Samuel C. | Kwong, Joseph | Welch, William R. | Samimi, Goli | Ozbun, Laurent | Bonome, Tomas | Birrer, Michael J. | Berkowitz, Ross S. | Wong, Kwong-Kwok

Article Type: Research Article

Abstract: Ovarian cancer is complex disease composed of different histological grades and types. However, the underlying molecular mechanisms involved in the development of different phenotypes remain largely unknown. Epidemiological studies identified multiple exogenous and endogenous risk factors for ovarian cancer development. Among them, an inflammatory stromal microenvironment seems to play a critical role in the initiation of the disease. The interaction between such a microenvironment, genetic polymorphisms, and different epithelial components such as …endosalpingiosis, endometriosis, and ovarian inclusion cyst in the ovarian cortex may induce different genetic changes identified in the epithelial component of different histological types of ovarian tumors. Genetic studies on different histological grades and types provide insight into the pathogenetic pathways for the development of different disease phenotypes. However, the link between all these genetic changes and the etiological factors remains to be established. Show more

Keywords: Ovarian cancer, microenvironment, inflammation, pathogenesis

Citation: Disease Markers, vol. 23, no. 5-6, pp. 367-376, 2007

Authors: Wong, Kwong-Kwok | Gershenson, David

Article Type: Research Article

Abstract: The role of serous tumors of low malignant potential (LMP) in the development of invasive epithelial cancer of the ovary is debatable. This review summarizes the current clinical, genetic, and genomic evidence for the existence of a continuum comprising both LMP serous tumors and low-grade serous ovarian carcinomas.

Keywords: K-Ras, B-Raf, Ki-67, p53, low malignant potential, low-grade serous ovarian carcinoma, genomics

Citation: Disease Markers, vol. 23, no. 5-6, pp. 377-387, 2007

Authors: Samimi, Goli | Ozbun, Laurent | Johnson, Michael E. | Mok, Samuel C. | Birrer, Michael J.

Article Type: Research Article

Citation: Disease Markers, vol. 23, no. 5-6, pp. 389-396, 2007

Authors: Badgwell, Donna | Bast Jr., Robert C.

Article Type: Research Article

Abstract: Despite advances in therapy, ovarian cancer remains the most deadly of the gynecological cancers. Less than 30% of women with advanced stage disease survive long-term. When diagnosed in stage I, up to 90% of patients can be cured with conventional surgery and chemotherapy. At present, only 25% of ovarian cancers are detected in stage I due, in part, to the absence of specific symptoms and to lack of an effective screening strategy. Early detection of ovarian …cancer might significantly improve the overall survival rate of women with ovarian cancer if 1) most cancers are clonal and unifocal, arising in the ovary rather than in the peritoneum, 2) metastatic disease results from progression of clinically detectable stage I lesions, and 3) cancers remain localized for a sufficient interval to permit cost-effective screening. Given the prevalence of ovarian cancer, strategies for early detection must have high sensitivity for early stage disease (> 75%), but must have extremely high specificity (99.6%) to attain a positive predictive value of at least 10%. Transvaginal sonography (TVS), serum markers and a combination of the two modalities have been evaluated for early detection of ovarian cancer. Among the serum markers, CA125 has received the most attention, but lacks the sensitivity or specificity to function alone as a screening test. Greater specificity can be achieved by combining CA125 and TVS and/or by monitoring CA125 over time. Two stage screening strategies promise to be cost effective, where abnormal serum assays prompt TVS to detect lesions that require laparotomy. Accrual has been completed for a 200,000 woman trial in the United Kingdom that will test the ability of a rising CA125 to trigger TVS and subsequent exploratory surgery. Given the heterogeneity of ovarian cancer, it is unlikely that any single marker will be sufficiently sensitive to provide an effective initial screen. Sensitivity of serum assays might be enhanced by utilizing a panel of biomarkers. Candidate biomarkers have been discovered through empirical development of monoclonal antibodies, studies of gene expression, cloning of gene families and proteomic techniques. The development of technologies that measure multiple serum markers simultaneously, linked to the creation of statistical methods that enhance sensitivity without sacrificing specificity hold great promise. Show more

Keywords: Ovarian cancer, screening, early detection, biomarkers

Citation: Disease Markers, vol. 23, no. 5-6, pp. 397-410, 2007

Authors: Kohn, Elise C. | Azad, Nilofer | Annunziata, Christina | Dhamoon, Amit S. | Whiteley, Gordon

Article Type: Research Article

Abstract: Novel technologies are now being advanced for the purpose of identification and validation of new disease biomarkers. A reliable and useful clinical biomarker must a) come from a readily attainable source, such as blood or urine, b) have sufficient sensitivity to correctly identify affected individuals, c) have sufficient specificity to avoid incorrect labeling of unaffected persons, and d) result in a notable benefit for the patient through intervention, such as survival or life quality improvement. Despite …these critical descriptors, the few available FDA-approved biomarkers for cancer do not completely fit this definition and their benefits are limited to a small number of cancers. Ovarian cancer exemplifies the need for a diagnostic biomarker of early stage disease. Symptoms are present but not specific to the disease, delaying diagnosis until an advanced and generally incurable stage in over 70% of affected women. As such, diagnostic intervention in the form of oopherectomy can be performed in the appropriate at-risk population if identified such as with a new accurate, sensitive, and specific biomarker. If early stage disease is identified, the requirement for survival and life quality improvement will be met. One of the new technologies applied to biomarker discovery is tour-de-force analysis of serum peptides and proteins. Optimization of mass spectrometry techniques coupled with advanced bioinformatics approaches has yielded informative biomarker signatures discriminating presence of cancer from unaffected in multiple studies from different groups. Validation and randomized outcome studies are needed to determine the true value of these new biomarkers in early diagnosis, and improved survival and quality of life. Show more

Keywords: Ovarian cancer, proteomics, mass spectrometry, biomarker, diagnosis

Citation: Disease Markers, vol. 23, no. 5-6, pp. 411-417, 2007

Authors: Merritt, William M. | Sood, Anil K.

Article Type: Research Article

Abstract: Tumor development and progression are inherently dependent on the process of angiogenesis. Recently, anti-angiogenic therapy has started to show promise as an effective treatment strategy in many solid tumors including ovarian carcinoma. Unfortunately, lack of effective biomarkers presents a challenge for oncologists in treatment planning as well as monitoring response of new anti-vascular agents. Previously, quantification of angiogenesis by microvessel density analysis provided useful prognostic information, however, its utility following anti-angiogenic therapy …remains to be determined. Moreover, since secreted cytokines play an active part in angiogenesis by mediating neovascularization in tumors, investigations have focused on their potential role to serve as candidate biomarkers of disease detection, prognosis, and treatment response. In this article, we review the role of key angiogenesis markers as potential biomarkers in ovarian carcinoma. Show more

Keywords: Angiogenesis, biomarker, ovarian carcinoma, therapy

Citation: Disease Markers, vol. 23, no. 5-6, pp. 419-431, 2007

Authors: Farley, John | Ozbun, Laurent | Samimi, Goli | Birrer, Michael J.

Article Type: Research Article

Keywords: Gynecologic, malignancies, biologiomarkers

Citation: Disease Markers, vol. 23, no. 5-6, pp. 433-443, 2007

Authors: Gimotty, Phyllis A. | Zhang, Lin | Alagkiozidis, Ioannis | Cadungog, Mark | Adams, Sarah | Chu, Christina | Katsaros, Dionysios | Coukos, George

Article Type: Research Article

Citation: Disease Markers, vol. 23, no. 5-6, pp. 445-452, 2007