The majority of epithelial ovarian carcinomas are of serous subtype, with most women presenting at an advanced stage. Approximately 70% respond to initial chemotherapy but eventually relapse. We aimed to find markers of treatment response that might be suitable for routine use, using the gene expression profile of tumor tissue. Thirty one women with histologically-confirmed latestage serous ovarian cancer were classified into 3 groups based on response to treatment (nonresponders, responders with relapse less than 12 months and responders with no relapse within 12 months). Gene expression profiles of these specimens were analyzed with respect to treatment response and survival (minimum 36 months follow-up). Patients' clinical features did not correlate with prognosis, or with specific gene expression patterns of their tumors. However women who did not respond to treatment could be distinguished from those who responded with no relapse within 12 months based on 34 gene transcripts (p < 0.02). Poor prognosis was associated with high expression of inhibitor of differentiation-2 (ID2) (p 5 0.001). High expression of decorin (DCN) and ID2 together was strongly associated with reduced survival (p 5 0.003), with an estimated 7-fold increased risk of dying (95% CI 1.9-29.6; 14 months survival) compared with low expression (44 months). Immunohistochemical analysis revealed both nuclear and cytoplasmic distribution of ID2 in ovarian tumors. High percentage of nuclear staining was associated with poor survival, although not statistically significantly. In conclusion, elevated expression of ID2 and DCN was significantly associated with poor prognosis in a homogeneous group of ovarian cancer patients for whom survival could not be predicted from clinical factors. ' 2006 Wiley-Liss, Inc.Key words: ovarian cancer; expression profiling; prognosis; treatment response; survival Ovarian cancer is the fifth leading cause of cancer death in women in the United States, with approximately 23,000 new cases and 14,000 deaths annually.1 The majority are epithelial ovarian carcinomas of the serous subtype. Most women present at an advanced stage when the disease has spread and, after surgery, platinum-based chemotherapy is the most widely used first-line treatment. Less than 20% of women with advanced cancer do not respond to initial chemotherapy; however, 70% respond initially but become platinum-resistant. Consequently, the 5-year survival for women with advanced disease is only 30%.
1,2Gene expression profiling using microarray technology offers improved classification and outcome prediction in a number of cancers.3-6 Expression profiling of ovarian cancer has identified candidate molecular markers, 7-10 differences between histopathologic subtypes or grades of cancer, 11,12 and patterns associated with suboptimal debulking. 13 A number of studies have evaluated gene expression profiling as a possible predictor of patient survival. Gene expression differences between short-and long-term survivors 14,15 and early relapse (at 21 months)...