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Biomedical subjects

A Berchuck

Publications and source records attributed to A Berchuck.

At least 145 records · Page 8Linked to original sources
PubMed1992

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. Similar fractions of rare alleles were found in DNA from ovarian cancers and from the peripheral blood of normal individuals. Thus, the frequency of unusual Ha-ras RFLPs did not distinguish patients with ovarian cancers from apparently healthy individuals.

Alleles↗
PubMed1992

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. Two of 20 frozen endometrial carcinoma specimens were also shown to contain a point mutation in Ki-ras codon 12. No correlation between ras mutation and a number of histologic or clinical parameters was observed. CONCLUSIONS: These data suggest a potential role for Ki-ras codon 12 mutations in the development of some (10%) endometrial cancers.

Cloning, Molecular↗
PubMed1992

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. Judging from preclinical models, interferon-gamma may be more active than interferon-alpha against human ovarian cancer. Although tumor necrosis factor-alpha can stimulate proliferation of some ovarian cancers, the cytotoxic activity of tumor necrosis factor-alpha has been amplified ex vivo by inhibitors of protein synthesis. Similar heterogeneity exists with regard to interleukin-1 where stimulation or inhibition of cell proliferation has been observed. Tumor-infiltrating lymphocytes from ascites fluid contain cells capable of major histocompatibility complex-restricted and major histocompatibility complex-nonrestricted cytotoxicity. Tumor-infiltrating lymphocytes and interleukin-2 have been combined with cytotoxic chemotherapy to treat advanced or recurrent disease. Bispecific monoclonal antibodies that react both with T cells and ovarian tumor cells have produced tumor inhibition in human tumor xenografts. Immunotoxins that contain OVB3 and pseudomonas exotoxin have been evaluated in a phase I clinical trial. Dose-limiting central neurotoxicity has been observed without tumor regression. A monoclonal antibody designated OVX1 has been developed against a high-molecular-weight mucinlike molecule associated with ovarian cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1992

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. The 75 cases were selected from a group of patients in whom the expression levels had already been assessed in a fresh-tissue IHC assay. An identical staining reactivity was observed in both formalin-fixed, paraffin-embedded tissue and fresh-frozen tissue in 48 of 50 (96%) epithelial ovarian cancers and in 23 of 25 (92%) primary breast cancers. Immunodetection of p53 in paraffin-embedded tissue blocks will be a useful alternative to the standard fresh-tissue assay and can accurately reflect the level of p53 expression in human tumors.

Antibodies, Monoclonal↗
PubMed1992

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. Fourteen of the patients were treated for their brain metastases; this included radiation therapy (RT; four), surgery and RT (one), RT and systemic chemotherapy (six), and all three treatment modalities (three). A meta-analysis was performed that combined the data from the current series with those of several recent clinical series that reviewed patients with brain metastases from ovarian carcinoma (67 patients total) to elucidate the impact of treatment and extent of disease on survival. RESULTS: In the current series, median survival (MS) after the diagnosis of brain metastases was 9 months. For the combined series, MS was 5 months. Thirteen patients who were treated with whole-brain RT and systemic chemotherapy (MS, 7 months), 10 patients who were treated with RT and surgery (MS, 10 months), and nine patients who were treated with all three modalities (MS, 16.5 months) had significantly longer survival than 19 patients who were treated with RT alone (MS, 3 months) (P = .05, P = .01, and P < .001, respectively). In a multivariate analysis, the only variable that provided prognostic information was treatment, namely the addition of systemic chemotherapy or surgery to RT for the treatment of brain metastases. CONCLUSION: Multimodal treatment of patients with brain metastases from ovarian cancer can result in significant palliation.

Adult↗
PubMed1992

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. RESULTS: Only 17% of patients had adequate skin incisions, 53% had pelvic washings, and 37% had omental biopsy at primary surgery. Complications of restaging laparotomy included 53% severe adhesions, 20% bowel complications, and 20% vascular complications requiring suture. Nine patients (30%) had disease upstaged and six (20%) had stage III disease established by comprehensive restaging laparotomy. Two-thirds of the upstaged patients had occult metastases identified only through cytology, random peritoneal biopsies, or selective lymphadenectomy. Women with poorly differentiated or papillary serous lesions were more likely to have disease upstaged than those with well- and moderately differentiated lesions or other histologic types (P < .05). Other clinicopathologic features did not predict upstaging. CONCLUSION: A comprehensive staging laparotomy is needed to detect occult metastatic disease in women with apparent early ovarian carcinoma.

Adult↗
PubMed1992

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. These women were compared to 277 patients with normal weight for height. RESULTS: The median age, incidence of diabetes mellitus and hypertension, number of nodes removed at lymphadenectomy, disease-free survival, length of hospital stay, and serious surgical or medical complications were the same in the two groups. However, obese patients had a significantly higher estimated blood loss, greater incidence of transfusion, and longer operative times. CONCLUSIONS: Survival is not compromised and the incidence of serious complications is not increased in obese patients treated with radical hysterectomy, but the operative technique is more difficult, the procedure lasts longer, and the surgery is associated with greater blood loss.

Adult↗
PubMed1992

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. Finally, for every oncogene that has been studied in ovarian cancer, there are at least a half-dozen that remain unexplored. In the future, when we have a better understanding of the molecular pathology involved in the development of ovarian cancer, this may allow us to better diagnose and treat, and eventually prevent, ovarian cancer.

Female↗
PubMed1992

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. Significant toxicity was minimal; none of these patients required surgery for bowel obstruction. Overall 5-year survival was 90 and 100%, but disease-free survival was only 65% (95% confidence interval [CI] 36-86%) and 60% (95% CI 12-81%) for patients with stage I and II disease, respectively. Two patients developed intraperitoneal and six systemic relapses; all patients received cisplatin regimens after relapse. Univariate analysis of age, stage, histology, Ovarian Cancer Study/Gynecologic Oncology Group risk status, lesion size, and presence or absence of capsular adhesions revealed that only an age of 50 or more years had an adverse effect on disease-free survival (P less than .03). This study suggests that determination of early-stage disease and host-tumor biology may be the most important factors in determining the survival of women with early ovarian cancer defined by comprehensive surgical staging. Intraperitoneal 32P does not appear to be effective adjuvant therapy in these women.

Adult↗
PubMed1991

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. The overall and disease-free survival rates were 86% and 75%, respectively, with no significant differences by stage, histologic grade, histologic type, or low-risk versus high-risk subsets recognized in patients who received comprehensive surgical staging. Seven (58%) of 12 patients had lymph node metastasis as the first site of recurrence, including two of three with late recurrences. Significant morbidity related to intraperitoneal chromic phosphate (32P) occurred in one (2%) woman. These results emphasize the need for comprehensive surgical staging of women with apparent early ovarian carcinoma to aid in the selection of appropriate initial adjuvant therapy.

Chromium↗
PubMed1991

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. p53 mRNA from three cancers that overexpressed the protein were sequenced and point mutations which altered the coding sequence of the highly conserved region of the gene were found in each case. Three cancers with undetectable protein levels also were sequenced and were found to be wild-type through the same region of the gene. As in other cancers, overexpression of the p53 protein in ovarian cancer appears to correlate closely with the presence of mutation in the p53 gene. p53 overexpression did not correlate with stage, histological grade, or the ability to perform optimal cytoreductive surgery. A significant correlation (P = 0.04) was observed between p53 overexpression and aneuploidy in advanced stage (III/IV) disease. There was no significant relationship between overall survival and p53 expression. Since mutation and overexpression of p53 are common in epithelial ovarian cancers, further studies are warranted to clarify the role of p53 in ovarian tumorigenesis.

Amino Acid Sequence↗
PubMed1991

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. Previously, small cell carcinoma of the vulva has been treated with regional therapy including surgery and radiation. Survival has been poor, however, due to the propensity of these tumors to metastasize early in the course of the disease. Recently, the median survival of patients with small cell carcinoma of the lung has been improved with the use of chemotherapy. The authors review the literature on the treatment of small cell carcinoma of the vulva and report on a patient who was treated successfully with vulvectomy and inguinal lymphadenectomy followed by adjuvant chemotherapy.

Adult↗
PubMed1991

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 2.5 ng/ml macrophage colony-stimulating factor, whereas only two of 80 apparently healthy donors (2.5%) had a comparable elevation of macrophage colony-stimulating factor. Circulating levels of macrophage colony-stimulating factor did not correlate with serum levels of CA 125. Moreover, 14 of 25 ovarian cancer patients (56%) with clinically evident disease and normal levels of CA 125 (less than 35 U/ml) had elevated levels of macrophage colony-stimulating factor. Among 29 patients with serum CA 125 levels less than 35 U/ml before positive surgical surveillance procedures, 9 (31%) had at least 2.5 ng/ml macrophage colony-stimulating factor. Elevated levels of macrophage colony-stimulating factor were also found in patients with carcinomas from other primary sites and in 31% of 134 patients with benign diseases. If intercurrent benign disease can be taken into account, macrophage colony-stimulating factor deserves further evaluation in combination with CA 125 in monitoring ovarian cancer.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1991

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 0.01). In addition, Scatchard analysis of binding of epidermal growth factor tagged with iodine 125 indicated the presence of high-affinity receptors in all of the ovarian epithelial cells and ovarian cancer cell lines. The number and affinity of receptors was similar in the normal epithelium and cancer cell lines, and there was no relationship between epidermal growth factor receptor number and responsiveness to epidermal growth factor. We conclude that human ovarian epithelial cells normally express epidermal growth factor receptors and that epidermal growth factor acts as a mitogen for these cells. Although the mitogenic response to epidermal growth factor often is attenuated in ovarian cancer cell lines, loss of responsiveness to epidermal growth factor does not appear to be due to decreased receptor expression.

Cells, Cultured↗
PubMed1991

Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease.

Prior studies have shown that overexpression of HER-2/neu occurs in one third of breast and ovarian cancers and that overexpression is associated with poor prognosis. We used a monoclonal antibody to assess immunohistochemically the level of HER-2/neu expression in normal and malignant endometrium. In 24 normal endometrial samples light to moderate (1+ to 2+) staining for HER-2/neu was seen in the glands, and there was no variation in intensity of staining during the menstrual cycle. Among 95 endometrial adenocarcinomas, nine (9%) were found to have heavier staining for HER-2/neu than was seen in normal endometrium (3+). High expression of HER-2/neu was found in 27% of patients with metastatic disease compared with 4% of patients with disease confined to the uterus (p less than 0.005). High HER-2/neu expression also was associated with absence of estrogen receptor (p less than 0.005) and with increased mortality from cancer. Further studies are needed to determine the significance of HER-2/neu overexpression in endometrial cancer.

Adenocarcinoma↗
PubMed1991

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. Even though multiple surgical procedures were performed in conjunction with sigmoid colectomy, 75% of the patients had no significant postoperative morbidity. Postoperative mortality was 2.5%. Seventy-eight percent avoided permanent colostomy. Despite the above morbidity rate and aggressive postoperative therapy, the median survival for the entire group was only 14.5 months, with no significant differences between groups of patients who were categorized by primary or secondary debulking, histologic grade, amount of preoperative disease, ascites, or extent of postoperative residual disease. Although a partial sigmoid colectomy can be performed with a reasonable morbidity rate as part of debulking for ovarian cancer, and probably provides significant palliation of symptoms from large pelvic tumors, it must be used judiciously in selected patients.

Carcinoma↗
PubMed1991

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. Among 87 ovarian cancers, however, 23% did not express immunohistochemically detectable receptor. Epidermal growth factor receptor expression was not related to histologic grade or stage, but was associated with poor survival (p less than 0.05). The median length of survival of patients with tumors that did not express epidermal growth factor receptor was 40 months compared with 26 months in patients with tumors that did express epidermal growth factor receptor. As in breast and bladder cancer, expression of epidermal growth factor receptor in ovarian cancer appears to be a poor prognostic factor.

Antibodies, Monoclonal↗