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The influence of estrogen (E) and antiestrogen (AES) on the in vitro growth of BG-1 ovarian carcinoma cells, which express steroid receptors was examined (K. R. Geisinger, T. E. Kute, M. J. Pettenati, C. E. Welander, Y. Dennard, L. A. Collins, and M. E. Berens, Characterization of a human ovarian carcinoma cell line with estrogen and progesterone receptors, Cancer 63, 280-288, 1989). All determinations were simultaneously referenced under similar conditions to MCF-7 cells, a well-established cell line for modeling hormonal responses in breast cancer. In "complete" media containing fetal calf serum (FCS, 10%), MCF-7 cell numbers increased approximately 7 x in 7 days, remaining at this level Days 8-15. In contrast, BG-1 cells achieved similar numbers by Day 7, but showed apparent exponential growth over Days 8-15 to 15-20 x. Phenol red-free media containing 10% FCS (less than 20 pg estradiol (E2)/ml by RIA) was used to assess responses to E and AES. Growth of both MCF-7 and BG-1 cells slowed in E-free media. E2 (10 nM) stimulated the growth of both cell lines, yet was responsible for exponential increases during Days 8-15 only in BG-1 cell numbers (50-70 x). The metabolically active AES (4OH-tamoxifen, 50 nM) reduced E2-stimulated MCF-7 growth to 3-4 x, while tamoxifen (50 nM) had no effect. Rescue with 10 microM E2 fully overcame the AES inhibition of MCF-7 proliferation. In contrast, BG-1 cells experienced significant E2-stimulated growth reductions in the presence of either 4OH-tamoxifen or tamoxifen. E2 was observed to rescue BG-1 cells from both of these antagonists. We conclude that BG-1 ovarian carcinoma cells respond in vitro to E and AES. Moreover, by virtue of responses to tamoxifen, BG-1 cells may have an intrinsic capacity to hydroxylate tamoxifen to its active metabolite. This property of ovarian carcinoma cells might be worth exploiting in the design of more effective combination chemotherapy regimens.

From November 1987 to January 1991, 1300 postmenopausal women underwent screening with transvaginal sonography (TVS). Women eligible for screening were all asymptomatic with no known ovarian tumors. Ovarian volume was calculated using the prolate ellipsoid formula, and a value in excess of 8.0 cm3 was considered abnormal. Ovarian abnormalities were detected in 33 women (2.5%), and 27 underwent exploratory laparotomy. Ovarian tumors were noted in all 27 patients, including 2 primary carcinomas and 14 serous cystadenomas. The two women with ovarian carcinomas had normal results of pelvic examinations and normal serum CA-125 levels. Both women had Stage I disease, and are alive and well after conventional therapy. TVS was time efficient, easy to perform, and well-accepted by patients. Currently, there are more than 3000 patient years of follow-up in the screened population, and there have been no deaths due to ovarian cancer. A multi-institutional trial to determine the efficacy of TVS as a screening method for ovarian cancer is indicated.

Karyotypic analysis of tumor specimens from 29 patients with untreated epithelial ovarian carcinoma was performed at the University of Kentucky Medical Center. Twenty-three of the twenty-nine tumors had adequate cells for analysis. Seventeen of these tumors exhibited chromosome abnormalities. Chromosome alterations were complex, with an average of seven different abnormal chromosomal patterns per tumor (range 2-14). Chromosomes 1 and 11 were the most commonly involved, being abnormal in 89 and 83% of tumors, respectively. Chromosomes 3 and 7 were also frequently abnormal. In contrast to invasive tumors, alterations in chromosomes 1 and 11 were not seen in the two tumors of borderline malignant potential. Evidence for DNA amplification of IGF2, Ha-ras-1, and c-ets was not observed. Amplification of the c-erbB-2 oncogene was present in two tumors. These findings indicate that multiple karyotypic abnormalities occur in untreated epithelial ovarian malignancies, with chromosomes 1 and 11 being the most frequently abnormal. These data also suggest that alterations of these chromosomes may be associated with the biologically aggressive behavior of frankly invasive ovarian tumors.

From November 1987 to April 1989, 1000 women 40 years or older underwent screening vaginal sonography at the University of Kentucky Medical Center (Lexington, KY). Patients included in this investigation were all asymptomatic and had no known pelvic abnormalities. Each ovary was measured in three planes and ovarian volume was calculated using the prolate ellipsoid formula. The upper limit of normal for ovarian volume was 18 cm3 in premenopausal women and 8 cm3 in postmenopausal women. In patients with normal scans, mean ovarian volumes decreased from 6.8 cm3 to 3.0 cm3 with menopause. Thirty-one patients (3.1%) had abnormal vaginal sonograms and 24 underwent exploratory laparotomy. All patients undergoing surgery had ovarian or fallopian tube tumors with dimensions identical to those predicted by ultrasound. Histologic diagnoses of these tumors included the following: adenocarcinoma, one, serous cystadenoma, eight; endometrioma, six; and cystic teratomas, two. Vaginal sonography was performed easily and without complications, and was well accepted by patients. All patients with normal sonograms have been rescreened annually and none have subsequently developed ovarian cancer. Further clinical trials to determine the efficacy of vaginal sonography as a screening method for ovarian cancer are indicated.

Ultrasonography was performed prior to operation upon 60 patients with tumors of the ovary. This procedure was accurate in differentiating tumors of the ovary from other types of tumors of the pelvis in more than 90 per cent of the patients. Likewise, a determination between benign and malignant lesions of the ovary could be reliably made on the basis of ultrasonic patterns. These findings suggest that ultrasonography should be performed on all patients suspected of having a tumor of the ovary.

From November 1973 to May 1986, 50 patients with Stage I epithelial ovarian cancer were treated at the University of Kentucky Medical Center (Lexington, KY) with oral Alkeran (melphalan) chemotherapy after primary surgery. Twenty-two patients had Grade 1 tumors, 23 patients had Grade 2 tumors, and five patients had Grade 3 tumors. Patients with ovarian tumors of borderline malignancy were excluded from this study. Twenty-eight patients received from six to 11 courses of chemotherapy and 22 patients completed 12 courses of chemotherapy. Chemotherapy was well tolerated and no patient died of chemotherapy-related complications. Thirty-eight patients underwent second-look laparotomy died of disease 41 months after diagnosis and one patient died with no evidence of disease 6 months after treatment. The actuarial survival of the total group of patients was 98% at 2 years and 94% at 5 years. Fewer than 12 months of chemotherapy may be necessary to obtain long-term survival in these patients.

Thirty-two patients with Stage III or IV epithelial ovarian cancer and residual tumor volumes in excess of 2 cm in diameter after initial debulking were treated with platinum and cyclophosphamide chemotherapy. Twenty-seven patients (84%) received at least six courses of chemotherapy. Six patients developed grade 3 or 4 hematologic toxicity and one patient died with granulocytopenia and sepsis. The actuarial survival of the total group of patients was 78% at 12 months, 27% at 24 months, and 11% at 36 month. Of patients with residual disease 2-4 cm in diameter, 82% were alive 12 months after diagnosis and 46% were alive at 24 months. In contrast, patients with greater than 4 cm residual disease had a 12-month survival of 73% and a 24-month survival of only 7%. The size of residual tumor after surgery remains a very important prognostic factor in patients treated with platinum-based combination chemotherapy. Reoperation with further tumor debulking should be considered in ovarian cancer patients referred for chemotherapy with large volume residual disease to maximize response to combination chemotherapy.

Four cases of immature teratoma of the ovary are presented and the recent literature is reviewed. The majority of these tumors were confined to one ovary at the time of diagnosis, and more than 75% occurred in women under 25 years of age. The two most important prognostic parameters were stage of disease and histologic grade. Optimal survival occurred when surgical tumor debulking was followed by combination chemotherapy. The addition of hysterectomy with contralateral adnexectomy did not improve the survival of patients with disease confined to one ovary. Similarly, postoperative radiation therapy was not shown to be beneficial in patients with this disease. Analysis of presently available data suggests that patients with teratocarcinoma of the ovary should be treated with tumor excision followed by at least 12 courses of chemotherapy with vincristine, actinomycin D, and cyclophosphamide. alpha-Fetoprotein may be useful as a biochemical marker of disease status in selected patients.

Immunohistochemical determinations of carcinoembryonic antigen, alpha-fetoprotein, human chorionic gonadotropin (hCG), and human placental lactogen (hPL) were performed on tissue sections from 137 epithelial ovarian cancers. Fewer than 25% of serous cystadenocarcinomas contained detectable amounts of any marker. Carcinoembryonic antigen was present in over 50% of tumors, and was noted most frequently in mucinous, endometrioid, and clear cell carcinomas. hPL was demonstrated in 30% of endometrioid carcinomas but was rarely present in other cell types. Both alpha-fetoprotein and hCG were noted in fewer than 10% of all major cell types of epithelial ovarian cancer. Forty-five patients had serial determinations of plasma levels of carcinoembryonic antigen at the time of regular follow-up visits. Serial plasma levels of carcinoembryonic antigen accurately predicated recurrence in nine of 16 patients whose tumors contained carcinoembryonic antigen, in contrast to two of 16 patients whose tumors were devoid of antigen.

Seven cases of ovarian dysgerminoma are presented and the recent literature reviewed. The majority of the cases reviewed had tumor confined to one ovary at the time of diagnosis, and nearly 50% occurred in women less than 20 years of age. The 5-year survival rate was 91% for 211 patients with stage I disease and 65% for 60 patients with stage II to IV dysgerminoma. The addition of contralateral adnexectomy, abdominal hysterectomy, and radiation therapy was not beneficial when disease was confined to one ovary. The survival of patients with advanced disease treated with chemotherapy was comparable with that of patients who received radiation. Analysis of the present data suggests that the use of unilateral oophorectomy should be limited to those patients with disease confined to one ovary and no histologic evidence of lymph node metastasis. Abdominal hysterectomy, bilateral adnexectomy, and adjuvant radiation is currently the treatment of choice for patients with more advanced dysgerminoma.

Endodermal sinus tumor of the ovary can be differentiated histologically and immunohistochemically from ovarian embryonal cell carcinoma. A case report of a patient with endodermal sinus tumor is presented in which a long-term remission was achieved by unilateral adnexectomy and combination chemotherapy. Review of the current literature indicates that tumor removal followed by combination chemotherapy with vincristine, actinomycin D, and cyclophosphamide is the most effective method of therapy for this highly malignant ovarian neoplasm. The addition of hysterectomy with contralateral ovariectomy or radiation therapy does not appear to significantly improve the survival of patients with this tumor. Serial plasma determinations of alpha fetoprotein provide biochemical monitoring of response to therapy and may be useful in predicting occult tumor recurrence.

From November 1, 1987, to July 1, 1988, 506 asymptomatic patients 40 years or older underwent screening vaginal sonography at the University of Kentucky Medical Center. Eligibility requirements included no known pelvic symptoms or clinical abnormalities, no history of pelvic radiation, and no history of ovarian cancer. Each ovary was measured in three planes and ovarian volume was calculated using the prolate ellipsoid formula. Ovarian morphology was classified as uniformly hypoechogenic, cystic, solid, or complex. The upper limit of normal for ovarian volume was 18 cm3 in premenopausal women and 8 cm3 in post-menopausal women. With respect to these criteria, 12 patients (2.4%) were noted to have abnormal sonograms, and 10 agreed to surgery. All 10 patients had ovarian tumors with dimensions equal to those predicted by ultrasound. These tumors included four serous cystadenomas, three endometriomas, two cystic teratomas, and one adenocarcinoma. Vaginal sonography is a relatively simple test that can detect subtle changes in ovarian size and morphology. Further evaluation of this test as a screening method for ovarian cancer should be performed in the setting of controlled clinical trials that emphasize cost control and strict patient follow-up.