The effect of antibodies and immunotoxins reactive with HER-2/neu on growth of ovarian and breast cancer cell lines.

Objective: Because HER-2/neu is overexpressed in one third of breast and ovarian cancers, we examined the effect of unconjugated monoclonal antibodies (ID-5, PB-3, TA-1) and an immunotoxin (TA-1-ricin) reactive with this protooncogene on the growth of breast and ovarian cancer cell lines.

Study Design: The tritiated thymidine incorporation assay was used to examine the effect of unconjugated antibodies on proliferation. A limiting dilution clonogenic assay was used to assess the effect of immunotoxin on cellular cytotoxicity.

Clonal origin of epithelial ovarian carcinoma: analysis by loss of heterozygosity, p53 mutation, and X-chromosome inactivation.

Background: It has been suggested that multiple sites of epithelial ovarian carcinoma on the peritoneal surface reflect polyclonal disease arising from multiple primary tumors in the peritoneal mesothelium, rather than monoclonal disease spread by metastases from one primary ovarian cancer.

Purpose: The purpose of this study was to investigate whether ovarian cancer has a monoclonal or polyclonal origin.

Methods: DNA specimens were obtained from peripheral blood lymphocytes (normal DNA) and from multiple tumor deposits of 17 women with epithelial ovarian carcinoma: primary tumors, metastatic deposits, and ascites.

The effect of interferon gamma on epidermal growth factor receptor expression in normal and malignant ovarian epithelial cells.

Objective: We examined the effect of interferon gamma on proliferation and epidermal growth factor receptor expression in ovarian cancer cell lines and normal ovarian epithelial cells.

Study Design: The tritiated thymidine incorporation assay was used to assess the effect of interferon gamma on proliferation. Scatchard analysis of anti-epidermal growth factor receptor antibody binding, and Western blotting of immunoprecipitates was used to assess the effect of interferon gamma on epidermal growth factor receptor expression.

Radical hysterectomy in obese women.

Objective: To determine whether there is a significant difference in treatment outcome and acute and chronic complications in obese compared with non-obese women having radical hysterectomy for early-stage cervical cancer.

Methods: From 1970-1985, 320 women underwent a class III radical hysterectomy and pelvic lymphadenectomy for stage IB-IIA invasive cervical cancer at Duke University Medical Center. Forty-three of these women weighed at least 80 kg and had a body weight greater than 25% above their ideal predicted weight.

Comprehensive restaging laparotomy in women with apparent early ovarian carcinoma.

Objective: To determine the yield and morbidity of comprehensive restaging laparotomy in women with presumed early ovarian carcinoma who have undergone incomplete initial staging procedures.

Methods: We conducted a retrospective review of 30 women with apparent early ovarian carcinoma who underwent a comprehensive restaging laparotomy including multiple random intraperitoneal biopsies and selective pelvic/para-aortic lymphadenectomy before receiving adjuvant therapy. Positive findings were compared with clinicopathologic features.

Fibronectin is an immunosuppressive substance associated with epithelial ovarian cancer.

Background: Although the ascites of patients with ovarian cancer has been reported to contain immunosuppressive factors, the identity and source of this activity has not been determined. Previously, the authors showed that conditioned media from two of four epithelial ovarian cancer cell lines inhibits proliferation of mitogen-stimulated human lymphocytes. The physical characteristics of the inhibitory substance are unlike those of peptide growth factors but closely resemble those of fibronectin.

Biology and therapy with biologic agents in gynecologic cancer.

Growth of epithelial ovarian cancer is influenced by several factors including transforming growth factor-alpha and transforming growth factor-beta, macrophage colony stimulating factor, tumor necrosis factor-alpha, interleukin-1 and interleukin-6, c-erb B-2 (HER-2/neu), and mutant p53. Continued expression of the epidermal growth factor receptor, new expression of c-fms, and overexpression of HER-2/neu are associated with a poor prognosis. A number of cytokines have been used to treat patients with ovarian cancer, including interferon-alpha, interferon-gamma, tumor necrosis factor-alpha, and interleukin-2.

Improved palliation of cerebral metastases in epithelial ovarian cancer using a combined modality approach including radiation therapy, chemotherapy, and surgery.

Purpose: Recent reports suggest an increasing incidence of CNS metastases in patients with ovarian cancer. We reviewed our experience in the management of brain metastases from ovarian carcinoma and merged our results with those of several other series reported in the literature to determine prognostic factors and the role of chemotherapy, radiation therapy, and surgery.

Patients And Methods: From 1977 to 1990, 15 of 795 patients who were treated for epithelial ovarian cancer at Duke University developed brain metastases.

Oncogenes in ovarian cancer.

The discovery of cancer-causing genes has provided us with the exciting opportunity to begin to understand the molecular pathology of ovarian cancer. Activation of several of these genes including HER-2/neu, myc, ras, and p53 has been described in some ovarian cancers (Table 2). In addition, some proto-oncogenes such as the EGF receptor (erbB) and the M-CSF receptor (fms) are expressed along with their respective ligands in some ovarian cancers.

p53 overexpression in formalin-fixed, paraffin-embedded tissue detected by immunohistochemistry.

Mutation and overexpression of the p53 gene have been noted in a wide range of human cancers and are thought to play a role in malignant transformation. Previously, immunohistochemical detection of p53 has been possible only in fresh-frozen tissues. We examined p53 expression in paraffin-embedded tissues from 50 epithelial ovarian cancers and 25 primary breast cancers with a modified immunohistochemical (IHC) technique developed in this laboratory, using monoclonal antibody (MAb) PAb1801.

Mutations of the Ki-ras oncogene in endometrial carcinoma.

Objective: The purpose of this study was to assess the extent of involvement of the ras oncogene in endometrial carcinoma.

Study Design: Genomic deoxyribonucleic acid from 30 samples of endometrial carcinoma was examined for point mutations in codons 12, 13, and 61 from the Ha-ras, Ki-ras, and N-ras genes by means of the polymerase chain reaction, slot-blotting, and deoxyribonucleic acid sequencing procedures.

Results: An apparent somatic mutation of Ki-ras codon 12 in one of 10 paraffin-embedded tumors was confirmed by deoxyribonucleic acid sequence analysis.

Adjuvant therapy with intraperitoneal chromic phosphate (32P) in women with early ovarian carcinoma after comprehensive surgical staging.

From 1974-1990, 23 women with stage I and five with stage II epithelial ovarian carcinoma received intraperitoneal chromic phosphate (32P) as the only form of adjuvant therapy after complete debulking and comprehensive surgical staging laparotomy. Surgery consisted of total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy, peritoneal washings for cytology, multiple biopsies of pelvic and abdominal peritoneum, and selective pelvic and para-aortic lymphadenectomy. Intraperitoneal 32P therapy was administered a median of 7 days after laparotomy.

Ha-ras polymorphisms in epithelial ovarian cancer.

Unusual restriction fragment length polymorphisms (RFLPs) of the Ha-ras locus have been found in DNA from leukocytes and tumor tissue of cancer patients. To determine whether rare alleles would be observed frequently in patients with ovarian cancer, Ha-ras RFLPs were studied in DNA from 42 different ovarian epithelial tumors and from the peripheral blood leukocytes of 76 normal individuals. Four common, seven intermediate, and seven rare alleles were detected overall.

Overexpression and mutation of p53 in endometrial carcinoma.

Immunohistochemical staining for the p53 protein was performed in 107 snap frozen primary endometrial adenocarcinomas and 15 benign uterine tissues using monoclonal antibody PAb1801. No staining was seen in benign samples, whereas intense nuclear staining of cancer cells consistent with overexpression of the p53 protein was observed in 22 of 107 cancers (21%). p53 overexpression was more frequent in advanced (Stage III/IV) cancers (41%) than in early (Stage I/II) cancers (9%) (P less than 0.

Regulation of growth of normal ovarian epithelial cells and ovarian cancer cell lines by transforming growth factor-beta.

Objective: The purpose of this study was to study the role of transforming growth factor-beta in regulation of proliferation of normal and malignant ovarian epithelial cells.

Study Design: We examined production of and responsiveness to transforming growth factor-beta in primary monolayer cultures of epithelial cells from five normal human ovaries and in five ovarian cancer cell lines.

Results: In normal ovarian epithelial cells, proliferation always was inhibited by transforming growth factor-beta (greater than 40%) (p less than 0.

Ploidy analysis of epithelial ovarian cancers using image cytometry.

We used a computerized image analysis system to determine the DNA content of 103 epithelial ovarian cancers using touch imprints of frozen tumor samples. Similar to prior studies of ploidy using flow cytometry, we found that most ovarian cancers (78%) were aneuploid while a minority (22%) were diploid. There was no relationship between ploidy and stage, histologic grade, or the ability to perform optimal cytoreductive surgery.

Increased serum levels of macrophage colony-stimulating factor in ovarian cancer.

Macrophage colony-stimulating factor is a cytokine that stimulates proliferation and differentiation of phagocytic cells. Macrophage colony-stimulating factor is produced by ovarian epithelial cancer cell lines and might provide a useful serum marker for the disease. Among sera from 69 patients with clinically apparent epithelial ovarian cancer, 47 (68%) had at least 2.

Adjuvant intraperitoneal chromic phosphate therapy for women with apparent early ovarian carcinoma who have not undergone comprehensive surgical staging.

Forty-nine women with apparent Stage I and II ovarian carcinoma received intraperitoneal phosphate 32 as the only adjuvant therapy after primary surgery. In addition to bilateral salpingo-oophorectomy, 40 (82%) had analysis of peritoneal cytology, and 35 (71%) underwent omentectomy. Random peritoneal biopsies and retroperitoneal lymph node sampling were not done in any of these patients.

Overexpression and mutation of p53 in epithelial ovarian cancer.

We examined p53 expression in 107 epithelial ovarian cancers with immunohistochemical techniques using monoclonal antibody PAb1801. High level expression of nuclear p53 protein was detected in the malignant epithelium in 54 (50%) of these cancers. Expression of p53 protein was undetectable in 13 benign gynecological tissues.

The role of partial sigmoid colectomy for debulking epithelial ovarian carcinoma.

Forty women underwent partial sigmoid colectomy during cytoreductive surgery for advanced epithelial ovarian carcinoma. Twenty-one (53%) and nineteen (47%) received this as part of primary or secondary debulking procedures, respectively. Fifty-four percent had postoperative residual disease less than 1 cm in largest diameter.

Stage I small cell carcinoma of the vulva treated with vulvectomy, lymphadenectomy, and adjuvant chemotherapy.

Neuroendocrine small cell carcinoma is a lethal, but rare, tumor that arises most frequently in the lung. Small cell cancer also rarely may occur in the female genital tract, usually in the cervix. This article concerns the fourth reported case of neuroendocrine small cell carcinoma of the vulva.

Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. II. Relationship between receptor expression and response to epidermal growth factor.

Previously we have shown that epidermal growth factor acts as a mitogen for some, but not all, ovarian cancer cells in culture. In this study we examined the effect of epidermal growth factor on proliferation of normal human ovarian epithelial cells in monolayer culture. We found that epidermal growth factor stimulated twofold to fourfold increases in proliferation in epithelial cells from each of five normal ovaries (p less than 0.

Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. I. Correlation of receptor expression with prognostic factors in patients with ovarian cancer.

Previous studies in breast and bladder cancer have suggested that epidermal growth factor receptor is expressed by only a proportion of cancers and is associated with poor clinical outcome. We used a monoclonal antibody specifically reactive with the extracellular domain of the epidermal growth factor receptor to localize this receptor immunohistochemically in frozen sections of normal ovary and epithelial ovarian cancer. Normal ovarian epithelium was found to express epidermal growth factor receptor in all cases.