Significantly greater expression of ER, PR, and ECAD in advanced-stage low-grade ovarian serous carcinoma as revealed by immunohistochemical analysis.

A 2-tier system that classifies ovarian serous carcinoma (OSC) as low grade or high grade is gaining acceptance. Women with low-grade OSC generally have higher 5-year survival rates than do women with high-grade OSC. We examined the expression of various markers to further understand the molecular differences between low-grade and high-grade OSCs: the potential therapeutic targets or prognostic markers Her-2/neu, estrogen receptor, and progesterone receptor (PR); the metastasis-associated markers cyclin D1 (BCL1), E-cadherin, matrix metalloproteinase (MMP) 2, and MMP-9; and the cell proliferation-associated markers BCL1, Ki-67 antigen (Ki-67), and p53. For this immunohistochemical analysis, we used paraffin-embedded specimens from 47 patients with advanced-stage low-grade OSC and from 49 patients with advanced-stage high-grade OSC. Our results showed that low-grade tumors expressed significantly higher levels of estrogen receptor, PR, and E-cadherin than did high-grade tumors, suggesting the involvement of gonadal steroid hormones, especially in the pathogenesis of low-grade OSC; the PR positivity was also observed in the stromal component of these low-grade tumors. On the other hand, high-grade tumors trended toward increased expression of MMP-9, BCL1, p53, and Ki-67, and robust MMP-9 positivity was observed in the stromal component of these high-grade tumors. These differences may lead to the development of different therapeutic strategies for women with either the low-grade or the high-grade form of OSC.

Comparison of the clinical behavior of newly diagnosed stages II-IV low-grade serous carcinoma of the ovary with that of serous ovarian tumors of low malignant potential that recur as low-grade serous carcinoma.

BACKGROUND: Serous ovarian tumors of low malignant potential (STLMP) frequently coexist with low-grade serous carcinoma of the ovary (LGSC) and, when they recur, frequently do so as LGSC. The purpose of this study was to compare the outcomes of patients with these two tumor types. METHODS: All patients with stages II-IV LGSC (group 1) or with STLMP that recurred as LGSC (group 2) seen at our institution from 1973 to 2003 were identified, and demographic data were obtained. For group 1, progression-free and overall survival times were calculated from the date of primary diagnosis to the date of disease progression/recurrence or the date of last contact/death, respectively. For group 2, progression-free and overall survival times were calculated from the date of first relapse as a LGSC to the date of progression or the date of last contact/death, respectively. The method of Kaplan and Meier was used to estimate survival, and the log-rank test was used to compare differences between survival curves. RESULTS: We identified 112 patients in group 1 and 41 in group 2. There were no statistically significant differences between the two groups in median age (42.7 vs. 45.4 years [at relapse]; P=0.37), progression-free survival time (19.5 vs. 25 months; P=0.92), or overall survival time (81.8 vs. 82.8 months; P=0.84). CONCLUSIONS: The age at diagnosis, progression-free survival time, and overall survival time associated with newly diagnosed stages II-IV LGSC of the ovary are similar to those of STLMP that recur as LGSC, providing further evidence of an association between these two tumor types.

The activity of taxanes compared with bleomycin, etoposide, and cisplatin in the treatment of sex cord-stromal ovarian tumors.

OBJECTIVE: We compared the efficacy and side effects of taxanes, with or without platinum, to bleomycin, etoposide, and cisplatin (BEP) in treating sex cord-stromal ovarian tumors. METHODS: We conducted a retrospective review of all patients with sex cord-stromal ovarian tumors seen at our institution from 1985 to 2002. Eligible patients were those who underwent pathologic confirmation, clinical evaluation, and treatment with a taxane or BEP for initial or recurrent disease. RESULTS: Of 222 patients identified, 21 received BEP for new (n = 11) or recurrent disease (n = 10); 44 received a taxane during 48 treatment episodes (four patients on two occasions each) for new (n = 11) or recurrent disease (n = 37). Newly diagnosed patients treated with BEP vs. taxanes had no significant difference in response rate (Fisher's exact test, P = 1), progression-free survival (PFS) (log-rank test, P = 0.213), or overall survival (log-rank test, P = 0.994). Among patients treated for recurrent measurable disease, the response rate was higher for BEP-treated (71%) than for taxane-treated patients (37%), but this was not statistically significant. In all patients treated for recurrent disease, there was no significant difference in failure to progress at chemotherapy completion between BEP- (70%) and taxane-treated patients (62%) or in median PFS (11.2 vs. 7.2 months). The presence of platinum in taxane-containing regimens correlated with response. Taxane-related side effects included neutropenia (n = 6), anemia (n = 1), thrombocytopenia (n = 1), myelodysplasia (n = 1), and hypersensitivity (n = 1). BEP-related side effects included pulmonary fibrosis (n = 3) and neutropenia (n = 2). CONCLUSIONS: Taxanes demonstrated activity against sex cord-stromal tumors of the ovary and may be less toxic than BEP. Taxane and platinum combination chemotherapy warrants further investigation in this disease.

The activity of taxanes in the treatment of sex cord-stromal ovarian tumors.

PURPOSE: To determine the efficacy and side effects of taxanes, with or without platinum, for the treatment of sex cord-stromal tumors of the ovary. PATIENTS AND METHODS: We conducted a retrospective review of all patients seen from 1985 to 2002 at The University of Texas M.D. Anderson Cancer Center with ovarian sex cord-stromal tumors. Eligible patients underwent pathology confirmation and clinical evaluation at M.D. Anderson and received a taxane for initial or recurrent disease. RESULTS: Of 222 patients identified, 44 were eligible for analysis. For nine patients treated in the first-line adjuvant setting, median progression-free survival (PFS) was not reached at 51 months. Of two patients treated for measurable disease in the first-line setting, one had a complete response. Median PFS was 34.3 months; median overall survival (OS) was not reached. Median follow-up was 90.3 months (range, 39.4 to 140.5 months). Response rate for 30 patients treated with a taxane +/- platinum for recurrent, measurable disease was 42%. Median PFS was 19.6 months; median OS was not reached. Median follow-up was 100.7 months (range, 8.1 to 361.3 months). The presence of platinum correlated with response in the recurrent, measurable disease setting. The number of patients was insufficient to detect relative efficacy of paclitaxel and docetaxel. Adverse effects of paclitaxel included neutropenia (n = 6), anemia (n = 1), thrombocytopenia (n = 1), myelodysplasia (n = 1), and hypersensitivity (n = 1). CONCLUSION: Taxanes seem to be active agents in the treatment of patients with sex cord-stromal tumors of the ovary. The combination of taxanes with platinum in the treatment of this disease deserves additional investigation.

Use of a vacuum-assisted closure device in the treatment of recurrent Paget's disease of the vulva.

BACKGROUND: Paget's disease of the vulva is a rare malignancy for which common recurrence is related to inadequate surgical margins. Excision with adequate surgical margins might leave a large defect that does not readily heal. CASE: A 41-year-old woman with recurrent Paget's disease of the vulva underwent a skinning excision of the vulva and perineum. A vacuum-assisted closure device was placed on the wound until final pathologic analysis confirmed the adequacy of surgical margins. CONCLUSION: The vacuum-assisted closure device not only allowed us to safely temporize wound closure until the final histopathologic results, but also helped secure the skin graft to the large and irregular surface. Additional studies are needed to determine the effectiveness of vacuum-assisted closure device therapy in Paget's disease of the vulva.

Overexpression of kallikrein 10 in epithelial ovarian carcinomas.

OBJECTIVE: We wanted to identify genes up-regulated in ovarian tumors that might serve as early markers for ovarian cancer. One promising focus is the family of genes that encode secreted proteases, which play essential roles in tumor invasion and metastasis. Kallikrein 10 (KLK10) is a member of the kallikrein family of serine proteases which include 15 proteins, including the prostate-specific antigen (PSA), also known as hK3. We investigated whether KLK10 and its related protein, hK10, might serve as equally accurate markers for ovarian carcinoma. METHODS: Transcriptional profiling was performed using RNA isolated from normal ovarian epithelium, ovarian cancer cell lines, and primary ovarian tumors. Microarray data were confirmed by Northern blot analysis of 66 ovarian tumor samples and 6 ovarian cancer cell lines. In situ hybridization and Western blot analysis confirmed the Northern blot findings. RESULTS: KLK10 was more highly expressed by primary ovarian tumors than by NOE. Thirty-two of 35 primary serous ovarian carcinoma samples (91.4%) expressed higher levels of KLK10 than NOE did. Eleven of 15 nonserous epithelial ovarian carcinoma samples (73.3%) and 8 of 11 primary peritoneal carcinoma samples (72.7%) also expressed KLK10. Overall, 84.8% of all epithelial ovarian and peritoneal carcinoma tumor samples showed elevated expression of KLK10. Similarly, Western blot analysis demonstrated that levels of the KLK10-related protein, designated hK10, are elevated in primary ovarian tissue lysates, but the protein is undetectable in immortalized ovarian epithelium. Finally, in situ hybridization established that KLK10 mRNA is much more highly expressed by tumor tissue than by normal epithelium and stromal tissues. CONCLUSIONS: Our data support recent immunoassay findings of elevated levels of hK10 in the tumor tissue and serum of ovarian cancer patients. Thus, it is likely that KLK10 and other kallikreins will serve as useful diagnostic and prognostic markers in patients with ovarian carcinoma.