Secretion of activin A in recurrent epithelial ovarian carcinoma.

OBJECTIVES: Activin A is a dimeric protein, composed of two beta-A subunits, that belongs to the TGF-beta family of growth factors. Most primary epithelial ovarian tumors (96%) synthesize and secrete activin protein in vitro and preliminary studies show that serum levels of activin are frequently elevated in women with epithelial ovarian cancer. Our objectives were to expand on studies of serum activin A levels in women with epithelial ovarian cancer and to determine whether levels of activin A correlate with the clinical course of disease. METHOD: Preoperative serum activin A levels were measured in 41 patients with epithelial ovarian cancer. In addition, serum activin A levels were measured in all available postoperative samples from the subset of these patients (n = 26) who had an elevated preoperative serum activin A level. Medical record information was used to compare each patient's serum levels of activin A to the clinical course of disease. RESULTS: Seventy-two percent of the stage III and IV patients (26/36), and none (0/5) of the stage I patients, had an elevated preoperative serum activin level. In postoperative samples, activin A levels were increased with persistent or recurrent (n = 9) stage III or IV ovarian cancer. Activin A levels dropped postoperatively and remained at or below the control level in patients in remission. CONCLUSION: Serum activin A levels correlate with recurrent or persistent disease in patients with epithelial ovarian cancer.

S-Phase fraction, p53, and HER-2/neu status as predictors of nodal metastasis in early vulvar cancer.

OBJECTIVE: Our aim was to determine the value of the S-phase fraction, p53, and HER-2/neu status as predictors of inguinal nodal metastasis in early vulvar cancer. METHODS: The charts of 100 consecutive patients with invasive squamous cell cancer of the vulva were reviewed and a cohort of patients with clinical stage I or II disease treated primarily with radical surgery and inguinal node dissection was identified. Within this cohort, all node-positive patients were matched with node-negative controls by depth of invasion. Tumor from the 13 node-positive patients and 26 controls was then analyzed by flow cytometry and immunohistochemistry. RESULTS: The median value of the S-phase fraction was higher in tumor from patients with inguinal nodal metastasis (median, 18.2; 25th-75th percentile: 13.9-28.3) than in node-negative patients (median, 8.9; 25th-75th percentile: 5.4-15.6) (P = 0.01). The presence of the HER-2/neu immunopositivity was also found to be associated with nodal metastasis (OR 4.05, 95% CI 1.0-16.6), but we found no evidence that DNA index or the presence of p53 immunopositivity was associated with nodal metastasis. CONCLUSION: Early vulvar cancer patients with inguinal node metastasis have a significantly higher S-phase fraction and are more likely to have HER-2/neu immunopositivity when compared to those without nodal metastasis.

Multiple immunoreactive inhibin proteins in serum from postmenopausal women with epithelial ovarian cancer.

Inhibin is an ovarian protein previously shown, using a nonspecific assay, to be elevated in serum of women with ovarian cancer. However, inhibin is secreted in multiple biochemical forms, including dimeric inhibin A and B and alpha inhibin precursors (pro-alphaC), each of which can now be specifically measured. We have examined the secretion of inhibin B and pro-alphaC inhibin in serum from women with epithelial ovarian cancer (EOC) for the first time, and have compared these analytes to inhibin A and total inhibin (inhibin A + B + pro-alphaC) as potential serum markers for EOC in postmenopausal women. Of all the immunoreactive inhibin proteins studied, the best serum marker was pro-alphaC, with 22% of women with EOC having levels that exceeded the range of values in women without EOC. Since CA 125 and pro-alphaC levels were not significantly correlated, combination of these markers resulted in 87% of EOC cases having elevated preoperative serum levels, a 9% increase over CA 125 alone. These data suggest that alpha inhibin secretion, especially pro-alphaC, may be useful in addition to CA 125 as a serum marker for EOC in postmenopausal women.

Malignant mixed mesodermal tumors of the ovary.

OBJECTIVE: To review the experience at Women & Infants Hospital and Hartford Hospital of patients with malignant mixed mesodermal tumors of the ovary, and to review the pertinent literature. METHODS: Fourteen cases of malignant mixed mesodermal tumors of the ovary at the two hospitals over a 5-year period were identified through their tumor registries. Demographic data, pathology, treatment, and survival rates were reviewed. RESULTS: The median survival of the patients in our series was 7 months, with 64% dead of disease in 1 year. A review of the pertinent literature indicated median survivals of 6-12 months, with more than 70% of the patients dead of disease at 1 year, despite treatment. CONCLUSION: Further investigation is needed to determine the proper management for malignant mixed mesodermal tumors of the ovary. Meanwhile, current treatment strategies should recognize the present therapeutic limitations, so as not to diminish any further the quality of life for women with this malignancy.

Prognostic significance of DNA content in epithelial ovarian cancer.

The prognostic significance of cellular DNA content of epithelial ovarian cancer as determined by flow-cytometric analysis of paraffin-embedded tumor blocks was investigated in 87 patients. Seventy-five percent of tumors were DNA aneuploid and 25% were DNA diploid. The survival at median follow-up for patients with DNA diploid tumors (68%) was significantly longer than for DNA aneuploid tumors (49%; P = 0.003). The other prognostic factors which significantly affected survival were stage (P < 0.0001), tumor grade (P < 0.006), and residual disease at completion of initial surgery (P = 0.0005). When patients were separated into low-stage and advanced-stage disease, DNA content was a significant prognostic variable for survival in Stage I and II patients (P = 0.05). In Stage III and IV patients, DNA content had no independent prognostic significance. There were 33 patients who underwent second-look surgery. Seven of 15 patients (47%) with negative second-look surgery were DNA aneuploid, whereas 17 of 18 patients (94%) with positive second-look surgery were DNA aneuploid. Therefore, there was a much higher likelihood of positive second-look in the DNA aneuploid group (17/24) compared to the DNA diploid group (1/9) (P = 0.003). In addition for those patients with negative second-look surgery, none (0/8) of the DNA diploid tumors recurred; however, 3 of 7 (43%) of the DNA aneuploid tumors recurred and died. Cox proportional/hazards analysis showed that DNA content is an independent prognostic factor for survival in epithelial ovarian cancer. Aneuploid DNA content in ovarian tumors is also correlated with more aggressive biologic behavior, and therefore, a worse clinical course.

Malignant mixed mullerian tumors of the fallopian tube.

Malignant mixed mullerian tumors of the female genital tract are rare and occur least commonly in the fallopian tube. A case is reported and 51 other cases in the literature are reviewed. The mean age at diagnosis is 59 years. Abdominal pain is the most common presenting complaint. A pelvic or abdominal mass is present in 75% of patients. The diagnosis is not usually established until surgery, with the most common preoperative diagnosis being ovarian malignancy. Seventy-five percent of cases had tumor extension beyond the fallopian tube at the time of surgery. Treatment has focused on surgery with postoperative radiation and/or chemotherapy. Prognosis is poor, with fewer than half of patients surviving 2 years. Recent reports suggest improved outcome with platinum-based chemotherapy but data are limited.

Serous carcinoma of the peritoneum after oophorectomy.

BACKGROUND: Prophylactic oophorectomy in premenopausal women has been recommended to prevent ovarian cancer. However, serous carcinoma of the peritoneum, which is indistinguishable from ovarian carcinoma, can occur after oophorectomy. CASES: Two cases are reported of serous carcinoma of the peritoneum after oophorectomy. Presentation, management, and outcome are similar to those for ovarian carcinoma. CONCLUSION: More data are needed to quantify the risk of carcinoma after oophorectomy. Such knowledge may change the risk-benefit calculations of recommending prophylactic oophorectomy to premenopausal women at a certain age, and must be discussed with the patient who is considering prophylactic oophorectomy with or without other planned surgery.

Predictive value of the fluorescent cytoprint assay (FCA): a retrospective correlation study of in vitro chemosensitivity and individual responses to chemotherapy.

The potential clinical usefulness of the fluorescent cytoprint assay (FCA) was assessed retrospectively in 73 cancer patients by correlating individual tumor chemosensitivity in vitro with responses to chemotherapy. The data show that the FCA has a sensitivity of 98%, specificity of 81%, and predictive accuracies of 85% and 97% for positive and negative clinical responses, respectively.

Rapid growth of human cancer cells in a mouse model with fibrin clot subrenal capsule assay.

Rapid in vivo growth of cultured human cancer or leukemia cells was achieved by implantation into the subrenal capsule of mice. A solid structure, necessary for accurate implantation and measurement of tumor growth in this model, was provided by stepwise addition of fibrinogen and thrombin to the tumor cells, leading to rapid enzymatic formation of a solid tumor-fibrin matrix. Human leukemia and epithelial cancers increased in volume between 6- and 40-fold when measured 6-10 days after implantation into normal or immunosuppressed mice. Immunosuppression of host CD-1 mice was achieved by cyclosporine given daily after tumor implantation, cyclophosphamide given preimplantation combined with cyclosporine, or whole-body irradiation given preimplantation. Confirming the validity of tumor measurements, tumor histology in the immunosuppressed mice revealed cell proliferation, invasion, and neovascularization. Similarly, no artifactual measurement of tumor growth was observed by nonviable cancer cells, implanted after in vitro exposure to a known cytotoxic concentration of thiotepa. This model provides an economical, short-term technique for the in vivo study of human tumor growth, for the evaluation of new cancer therapies, and for in vitro - in vivo drug activity correlations in specific types of human cancer or leukemia cell lines.

Use of a clinical laboratory computer to warn of possible drug interference with test results.

Using a clinical laboratory computer system, software has been developed which checks to determine if the result of any test performed on a patient specimen may be affected by any drug administered to that same patient. If possible interference is detected, a comment is automatically attached to the result on the patient's computer-generated report warning the attending physician the result may be falsely elevated or lowered.