The clinical significance of blood transfusion at the time of radical hysterectomy.
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Blood Transfusion↗
Biomedical subjects
A Berchuck
Publications and source records attributed to A Berchuck.
Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer.
Previous studies have suggested that overexpression of HER-2/neu oncogene occurs in 15-40% of breast cancers and that overexpression is associated with poor prognosis. In the present report, we have used an immunohistochemical technique involving a monoclonal antibody specifically reactive with the external domain of HER-2/neu to study expression of HER-2/neu in frozen sections of normal ovary and advanced epithelial ovarian cancer. The intensity of staining for HER-2neu was always moderate or less (0-2+) in normal ovarian epithelium. Among 73 ovarian cancers, 50 (68%) had staining similar to that for normal ovarian epithelium (0-2+) while 23 (32%) stained heavily (3+). Survival of the 23 patients with high HER-2/neu expression (median, 15.7 months) was significantly worse (P = 0.001) than that of the 50 patients (median, 32.8 months) with normal HER-2/neu expression. In addition, patients whose tumors had high HER-2/neu expression were significantly less likely to have a complete response to primary therapy (P less than 0.05) or have a negative second-look laparotomy when serum CA 125 levels were normal preoperatively (P less than 0.05). These findings suggest that HER-2/neu deserves further evaluation as a prognostic marker in epithelial ovarian cancer.
Female↗
Gynecologic tumor markers.
The advent of monoclonal technology has increased the potential utility of antibody-dependent tumor marker assays in gynecologic oncology. The availability of unlimited quantities of several pure monoclonal antibodies directed against novel epitopes on tumor-associated antigens has permitted development of highly sensitive assays for serum markers. Traditional assays for human chorionic gonadotropin (hCG), NB/70K and TA-4 have been improved. CA 125 has provided a useful first-generation marker for monitoring ovarian cancer and triaging patients with pelvic masses, despite limitations in sensitivity and specificity. In the next decade, the challenge is to identify new markers that will complement CA 125 in monitoring ovarian cancer and facilitate screening for occult early-stage disease. Strategies involving multiple markers and modalities may be required. Some markers may emerge through a more fundamental knowledge of the biology of gynecologic neoplasms, including the expression of growth factors and their receptors. Finally, the application of monoclonal antibodies to immunohistochemistry and radionuclide imaging also may provide new areas of diagnostic application for monoclonal antibodies in gynecologic oncology.
Antibodies, Monoclonal↗
The prognostic significance of CA 125 half-life in patients with ovarian cancer who have received primary chemotherapy after surgical cytoreduction.
Fifty-four patients with advanced epithelial ovarian cancer were monitored with serial serum CA 125 levels after surgical cytoreduction and during multi-agent chemotherapy with cisplatin-containing regimens. CA 125 half-life of less than 20 days was associated with prolonged overall survival (p less than 0.015). In those patients who eventually were found to be disease-free at surgical surveillance procedures, normalization of serum CA 125 levels to less than 35 U/ml within 65 days of primary operation also suggested an improved survival (p less than 0.059).
Adenocarcinoma, Mucinous↗
Preoperative evaluation of serum CA 125, TAG 72, and CA 15-3 in patients with endometrial carcinoma.
We evaluated 109 women with endometrial carcinoma to determine the accuracy of preoperative tumor-associated antigen levels (CA 125, CA 72, CA 15-3) for prediction of extrauterine disease and whether TAG 72, CA 15-3, or both would improve the predictive value of CA 125 alone. Eleven (12%) of 80 patients with disease confined to the uterus or positive cytologic findings had CA 125 values greater than 35 U/ml versus 12 (65%) of 20 patients with extrauterine metastasis. Therefore CA 125 values had sensitivity of 65% and specificity of 88%. The TAG 72 level was elevated (greater than 6 U/ml) in 4% of patients with localized disease and 30% with metastasis. CA 15-3 was elevated (greater than 30 U/ml) in 17% and 65% in these categories, respectively. TAG 72 or CA 15-3 levels did not improve the combination of sensitivity and specificity of CA 125 alone. In addition, only one of 10 patients with microscopic metastasis (three cases) or positive peritoneal cytology (seven) had elevation of any of these tumor-associated antigen levels. Failure to detect occult metastasis and a high false-positive rate limit the role of these tumor-associated antigen assays in the preoperative evaluation of patients with endometrial carcinoma.
Antigens, Neoplasm↗
Heterogeneity of antigen expression in advanced epithelial ovarian cancer.
Immunohistochemical techniques were used to evaluate the expression of six antigens (CA 125, TAG 72, CA 19-9, OVTL3, DF3, and transferrin receptor) in frozen sections from the primary tumor and metastases of 20 patients with epithelial ovarian cancer. Heterogeneous expression of most antigens was observed within a given tumor nodule, but in each patient the proportion of cells expressing an antigen was similar in the primary tumor and metastases. To explore the stability of the antigenic phenotype of individual cells, we studied CA 125 expression in an ovarian cancer cell line. Cells were separated into CA 125-positive and -negative groups using fluorescence-activated cell sorting. After the two groups of cells were recultured separately, only 38% of cells originally sorted as CA 125 positive still expressed CA 125, whereas 27% of cells sorted as CA 125 negative expressed CA 125. That cells may gain or lose CA 125 expression in culture suggests that expression of CA 125 by ovarian cancer cells is not a stable trait.
Adenocarcinoma↗
High-dose alkylating agent chemotherapy with autologous bone marrow support in patients with stage III/IV epithelial ovarian cancer.
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Adult↗
Treatment of endometrial stromal tumors.
We reviewed 31 cases of endometrial stromal tumors treated on the Gynecology Service at Memorial Sloan-Kettering Cancer Center from 1970 to 1984. Twenty-two patients had endolymphatic stromal myosis and 9 patients had endometrial stromal sarcoma. Twenty-six patients initially had disease confined to the uterus. Following hysterectomy, 7 patients received various adjuvant therapies, but no active adjuvant regimen was identified. All 3 patients who presented with advanced endometrial stromal sarcoma died of rapidly progressive disease; only 2 of 6 patients with stage I endometrial stromal sarcoma developed recurrence. Among patients with endolymphatic stromal myosis, a higher recurrence rate was noted in patients with residual ovarian tissue (100%) than in those without residual ovarian tissue (43%). Fifteen patients were treated for recurrent disease (13 with endolymphatic stromal myosis, 2 with endometrial stromal sarcoma). Following attempts to resect disease surgically, objective responses were attained with both chemotherapy (57%) and radiation (40%). The median survival following treatment of recurrent disease was 46 months. Actuarial survival for all patients in this study was 76% at 5 years and 69% at 10 years.
Adult↗
Adjuvant radiotherapy following radical hysterectomy for patients with stage IB and IIA cervical cancer.
From 1971 through 1984, 320 women underwent radical hysterectomy as primary therapy of stage IB and IIA cervical cancer. Two hundred forty-eight patients (78%) were treated with surgery alone and 72 patients (22%) received adjuvant postoperative external-beam radiotherapy. Presence of lymph node metastasis, large lesion (greater than 4 cm in diameter), histologic grade, race (noncaucasian), and age (greater than 40 years) were significant poor prognostic factors for the entire group of patients. Patients treated with surgery alone had a better disease-free survival than those who received combination therapy (P less than 0.001). However, patients receiving adjuvant radiation therapy had a higher incidence of lymphatic metastases, tumor involvement of the surgical margin, and large cervical lesions. Adjuvant pelvic radiation therapy did not improve the survival of patients with unilateral nodal metastases or those who had a large cervical lesion with free surgical margins and the absence of nodal involvement. Radiation therapy appears to reduce the incidence of pelvic recurrences. Unfortunately, 84% of patients who developed recurrent tumor after combination therapy had a component of distant failure. The incidence of severe gastrointestinal or genitourinary tract complications was not different in the two treatment groups. However, the incidence of lymphedema was increased in patients who received adjuvant radiation therapy. Although adjuvant radiation therapy appears to be tolerated without a significant increase in serious complications, the extent to which it may improve local control rates and survival in high-risk patients appears to be limited. In view of the high incidence of distant metastases in high-risk patients, consideration should be given to adjuvant systemic chemotherapy in addition to radiation therapy.
Adolescent↗
The role of tumor markers in gynecologic oncology.
Human chorionic gonadotropin is a highly sensitive and specific tumor marker for gestational trophoblastic neoplasia that accurately reflects tumor volume and the clinical course of disease. In women with endodermal sinus tumors and embryonal carcinomas, alpha-fetoprotein usually is a reliable marker, and it accurately predicts the presence of yolk sac elements in mixed germ cell tumors. CA 125 is the most widely utilized tumor marker presently available for use in patients with epithelial ovarian cancer. It has utility in monitoring therapy and differentiating benign from malignant pelvic masses. Measurement of serial CA 125 levels in postmenopausal women may facilitate screening for occult early stage disease. In the future, monoclonal antibodies that recognize tumor-associated antigens may prove useful for radionuclide imaging.
Antibodies, Monoclonal↗
Expression of epidermal growth factor receptor and HER-2/neu in normal and neoplastic cervix, vulva, and vagina.
Monoclonal antibodies were used to localize immunohistochemically epidermal growth factor receptor and HER-2/neu in normal and neoplastic frozen tissue samples from the lower genital tract of women. In squamous epithelia of the cervix, vulva, and vagina, epidermal growth factor receptor and HER-2/neu both were expressed most strongly by basal keratinocytes. Expression of both of these cell surface molecules decreased as cells underwent differentiation toward the mucosal surface. In contrast, both epidermal growth factor receptor and HER-2/neu were expressed throughout the entire thickness of the epithelium by undifferentiated squamous cells in squamous metaplasia, raised condyloma, and carcinoma in situ. In 34 squamous cancers of the cervix, vulva, and vagina, all malignant cells were found to have moderate to heavy staining for epidermal growth factor receptor. Staining of 33 of these cancers for HER-2/neu was light, although one patient who presented with distant metastases had heavy staining for HER-2/neu. These data suggest that although overexpression of HER-2/neu in squamous cancers of the lower genital tract is a rare event, it may be associated with aggressive biologic behavior.
Adenocarcinoma↗
Computed tomography-guided fine-needle aspiration of retroperitoneal lymph nodes in gynecologic oncology.
Computed tomography-guided fine-needle aspiration was performed on 30 retroperitoneal lymph nodes in 29 patients with gynecologic cancer. There were no serious complications. Review of the cytologic material demonstrated malignant cells in 83% of the aspirates. Because the predictive value of a positive aspirate approaches 100%, therapy for metastatic disease can be initiated in these patients with the need for an open biopsy. Among five aspirates in which malignant cells were not seen, the cellularity of the specimen appeared to be the critical factor determining the predictive value of the aspirate. Whereas neither of two patients with negative aspirates of adequate cellularity has developed recurrent disease, two of three patients with hypocellular negative aspirates have. Because a hypocellular negative aspirate from a retroperitoneal lymph node may not be a true reflection of disease status, either repeat aspiration or open biopsy is advisable.
Adenocarcinoma↗
The role of peptide growth factors in epithelial ovarian cancer.
We studied the effect of epidermal growth factor, platelet-derived growth factor, fibroblast growth factor, and transforming growth factor-beta on proliferation of four epithelial ovarian cancer cell lines (OVCA 420, OVCA 429, OVCA 432, and OVCA 433). Epidermal growth factor stimulated growth of OVCA 429 cells (P = .0001) and OVCA 433 cells (P = .0002). Platelet-derived growth factor did not stimulate growth of any of the cell lines. Fibroblast growth factor stimulated growth of OVCA 420 cells (P = .003). Transforming growth factor-beta inhibited growth of OVCA 420 cells (P = .0001), OVCA 432 cells (P = .003), and OVCA 433 cells (P = .004). To detect production of known growth factors by the cancer cell lines, we tested the effect of cancer cell-conditioned media on proliferation of cell lines known to respond to growth factors. Only media exposed to OVCA 433 cells were found to contain activity that mimicked one of the known growth factors (transforming growth factor-beta). These results suggest that individual ovarian cancers vary widely in their response to and production of known peptide growth factors. Finally, we found that OVCA 429-conditioned medium significantly inhibited proliferation of mitogen-stimulated lymphocytes (P less than .0001). The characteristics of this immunosuppressive factor were distinct from those of transforming growth factor-beta. Production of this factor by an immortalized cell line provides a unique opportunity to identify an immunosuppressive substance associated with ovarian cancer.
Cell Division↗
A comparison of symptomatology, physical examination, and vaginal cytology in the detection of recurrent cervical carcinoma after radical hysterectomy.
To evaluate our surveillance program for recurrent cervical carcinoma, we reviewed patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stages IB and IIA cervical cancer. The study group consisted of 203 women followed at Duke University Medical Center exclusively who had at least 2 years of regular surveillance. Thirty-one (15%) developed recurrence. For the detection of recurrent tumor, vaginal cytology had a sensitivity and specificity of 13 and 100%, pelvic or general physical examination 58 and 96%, and the presence of suspicious symptoms 71 and 95%, respectively. Ninety-four percent of all patients with recurrent tumor had at least one abnormal surveillance index. Three of 31 patients (10%) with recurrent tumor were treated successfully with secondary therapy. Two recurrences were detected by vaginal cytology exclusively. Even though vaginal cytology is not sensitive and may not be cost-effective, we conclude that it is the technique most likely to detect recurrent tumor while it is localized and potentially curable.
Female↗
Immunohistochemical expression of CA 125 in endometrial adenocarcinoma: correlation of antigen expression with metastatic potential.
Immunohistochemical localization of CA 125 using murine monoclonal antibody OC 125 was performed on fresh frozen tissue from 44 endometrial adenocarcinomas and 26 benign endometria. Immunohistochemical evaluation incorporated both intensity and distribution of staining (CA 125 HSCORE). Thirty-seven cancers (84%) and 23 benign endometria (88%) expressed immunohistochemically detectable CA 125. Staining was confined to epithelial cells and was present both on the cell membrane and in the cytoplasm. Among the 44 endometrial cancers, CA 125 HSCORE did not correlate with histological grade, depth of myometrial invasion or estrogen/progesterone receptor levels. Following surgical staging, 13 patients (30%) were found to have extrauterine metastatic disease. The median CA 125 HSCORE of patients with metastatic disease (2.25) was significantly higher than that of patients with disease confined to the uterus (0.6) (P less than 0.001). In addition, high CA 125 HSCORE also correlated with the presence of lymph node metastasis (P less than 0.001). The results of this study suggest that high CA 125 expression by endometrial adenocarcinomas is associated with increased metastatic potential.
Adenocarcinoma↗
Epidermal growth factor receptor expression in normal and malignant endometrium.
Epidermal growth factor receptor expression in fresh-frozen uterine tissues was studied with the use of monoclonal antibody 528, which recognizes an epitope on the external domain of the epidermal growth factor receptor. Immunohistochemically detectable epidermal growth factor receptor was seen in all uterine cell types in 19 of 20 normal uteri. Staining of endometrial glands and endometrial stromal cells was consistently greater than that of myometrium, and no variation in intensity or distribution of staining was seen during the menstrual cycle. Immunohistochemically detectable epidermal growth factor receptor was found less frequently in endometrial adenocarcinomas than in normal endometrium (p less than 0.01). Thirteen of 40 endometrial adenocarcinomas (32.5%) did not express detectable receptor. Epidermal growth factor receptor expression did not correlate with histologic grade, depth of myometrial invasion, estrogen-progesterone receptor status, the presence of extrauterine metastases, or the development of recurrent disease.
Adenocarcinoma↗
Immunohistochemical expression of TAG-72 in normal and malignant endometrium: correlation of antigen expression with estrogen receptor and progesterone receptor levels.
TAG-72 is a tumor-associated antigen that is expressed by secretory endometrium and most endometrial adenocarcinomas. We used immunohistochemical techniques to quantitate expression of TAG-72, estrogen receptor, and progesterone receptor in 21 normal endometria and 44 endometrial adenocarcinomas. In normal cycling endometrial glands, TAG-72 expression was related inversely to expression of receptors for estrogen and progesterone. This suggests that TAG-72 expression in normal endometrium may be hormonally regulated. Ninety-one percent of endometrial adenocarcinomas expressed immunohistochemically detectable TAG-72. The magnitude of TAG-72 expression did not correlate with other known prognostic factors in endometrial cancer such as histologic grade, depth of myometrial invasion, surgical stage, or steroid receptor status. The production of TAG-72 by most endometrial adenocarcinomas may represent nonspecific expression by cells that have dedifferentiated.
Adult↗
Pneumoperitoneum due to peritoneovaginal fistula following hysterectomy.
A patient with pneumoperitoneum that developed due to peritoneovaginal fistula following hysterectomy is presented. In addition, we have reviewed the literature and formulated guidelines for the management of this problem. Most patients present following sexual intercourse and in many cases the fistula can be diagnosed radiographically. Laparotomy may be avoided if the cause of the fistula is suspected. Surgical closure of the fistula may be unnecessary since spontaneous closure occurs frequently.
Adult↗