Array comparative genomic hybridization (aCGH) and microarray expression profiling were used to subclassify DNA and RNA alterations associated with differential response to chemotherapy in ovarian cancer. Two to 4 Mb interval arrays were used to map genomic imbalances in 26 sporadic serous ovarian tumors. Cytobands 1p36, 1q42-44, 6p22.1-p21.2, 7q32.1-q34 9q33.3-q34.3, 11p15.2, 13q12.2-q13.1, 13q21.31, 17q11.2, 17q24.2-q25.3, 18q12.2, and 21q21.2-q21.3 were found to be statistically associated with chemotherapy response, and novel regions of loss at 15q11.2-q15.1 and 17q21.32-q21.33 were identified. Gene expression profiles were obtained from a subset of these tumors and identified a group of genes whose differential expression was significantly associated with drug resistance. Within this group, five genes (GAPD, HMGB2, HSC70, GRP58, and HMGB1), previously shown to form a nuclear complex associated with resistance to DNA conformation-altering chemotherapeutic drugs in in vitro systems, may represent a novel class of genes associated with in vivo drug response in ovarian cancer patients. Although RNA expression change indicated only weak DNA copy number dependence, these data illustrate the value of molecular profiling at both the RNA and DNA levels to identify small genomic regions and gene subsets that could be associated with differential chemotherapy response in ovarian cancer.

In order to determine whether recent methods of diagnosis and treatment have resulted in an improved survival for patients with uterine sarcoma, we reviewed 99 cases treated in our center from 1970-1985. Morphologic characteristics of 74 tumors were specifically reassessed for this study. All tumors were graded. Of 42 Stage I cases that were morphologically assessed, tumor-positive pelvic lymph nodes were found in two of the 15 patients in whom sampling was done. No cases of tumor-positive para-aortic nodes were found in 14 patients with Stage I disease. In Stage I and Stage II, no cases of positive para-aortic nodes were found in association with negative pelvic nodes. The 2- and 5-year survival rates in Stage I were 47.4% and 29.4%, respectively. Local recurrence decreased (p less than 0.01) in Stage I from nine of 22 cases in which operation alone was performed to none of 15 cases in which pelvic radiotherapy was added, but no improvement in the 5-year survival rate was observed. As with lymphadenectomy and radiotherapy, the recent use of chemotherapy for uterine sarcoma had no impact on survival.