Purpose: Patients with ovarian clear cell adenocarcinoma generally have a poor response to combination chemotherapy and have overall poorer prognosis than patients with other histologic types of ovarian cancer. Genetic changes in this group of cancer have not been thoroughly explored.Identification of these changes may provide us new therapeutic targets to treat this disease. Experimental Design: Genomic and expression array analyses were applied on 30 clear cell ovarian cancer cases and 19 serous cases using a 10,816-element cDNA microarray platform. Further validation and clinical correlation studies were done on differentially expressed genes that are related to chemoresistance. Results: Based on array analyses, 12 genes showed a significant increase in DNA and mRNA copy number and 5 genes showed a significant decrease in DNA and RNA copy number in clear cell tumors compared with those in the serous type. One of the genes was ABCF2, which belongs to theATP-binding cassette gene superfamily and has been shown to amplify in other tumor types. Validation studies were done using real-time quantitative PCR and immunohistochemistry. The results showed significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases. Furthermore, in 20 clear cell cases with chemoresponse data available, ABCF2 cytoplasmic staining was significantly higher in nonresponders than that in the responders (60.0% versus 28.5%; P = 0.0002). Conclusions: These data suggest that ABCF2 protein may be a prognostic marker for ovarian clear cell ovarian adenocarcinoma.Ovarian cancer is the fifth most common form of cancer in women in the United States, accounting for 4% of the total number of cancer cases and 25% of those cases occur in the female genital tract. It was estimated that 14,300 deaths would be caused by ovarian cancer in the year 2005 (1). Ovarian cancer can be subdivided into four major histologic types. Among them, clear cell ovarian cancer, which constitutes 5% to 10% of ovarian cancer cases, differs from the other histologic types with respect to its clinical characteristics (2, 3). This type of tumor is thought to sometimes arise from endometriosis and many of the patients present the disease at early stages (2, 3). Clear cell type is usually more resistant to systemic chemotherapy than other types and has a worse prognosis (4, 5). In fact, in current clinical practice, patients with clear cell type ovarian cancer are treated as those with high-grade neoplasms (6). The molecular pathobiology of clear cell type ovarian cancer remains largely unknown.Recent studies showed that 25% to 75% of clear cell type ovarian cancer showed increased DNA copy numbers on 8q11-q13, 8q21-q22, 8q23, 8q24-qter, 17q25-qter, and 20q13-qter and decreased copy number on 19p by chromosome comparative genomic hybridization (CGH; ref. 7). However, changes in the DNA copy number on the gene level have not been identified. Using oligonucleotide array expression profiling, Schwartz et al. ...
Chemotherapy-induced neutropenia is a common complication in cancer treatment. In this study, we investigated chemotherapy-induced neutropenia that was recently detected in all patients with gynecologic malignancy. Between January 2009 and December 2011, we examined cases of chemotherapy-induced neutropenia reported in our hospital. We analyzed the incidence and clinical features of chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. During the study period, we administered over 1614 infusions (29 regimens) to 291 patients. The median age of the patients was 60 years (range 24–84 years). Chemotherapy-induced neutropenia occurred in 147 (50.5%) patients over 378 (23.4%) chemotherapy cycles. Febrile neutropenia occurred in 20 (6.9%) patients over 25 (1.5%) cycles. The mean duration of neutropenia and fever was 3.6 days (range 1–12 days) and 3.4 days (range 1–9 days), respectively. The source of fever was unexplained by examination or cultures in 14 (56.0%) cycles. There were two cases of neutropenia-related death. Chemotherapy-induced neutropenia was associated with older age (over 70 years) (P<0.0001), less than five previous chemotherapy cycles (P=0.02), disseminated disease (P=0.03), platinum-based regimens (P<0.0001), taxane-containing regimens (P<0.0001), and combined therapy (P<0.0001). Febrile neutropenia was associated with poor performance status (P<0.0001), no previous chemotherapy (P<0.05), disseminated disease (P<0.0001), and distant metastatic disease (P=0.03). Neither chemotherapy-induced neutropenia nor febrile neutropenia was associated with bone marrow metastases or previous radiotherapy. By identifying risk factors for febrile neutropenia, such as performance status, no previous chemotherapy, disseminated disease, and distant metastatic disease, the safe management of chemotherapy-induced neutropenia may be possible in patients with gynecologic malignancy.
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