Malignant disease in pregnancy.

Cancers in pregnancy are uncommon but do occur with an average frequency of 1 in 1,000 births. This gives rise to opposing emotional reactions in these women: they are happy they are pregnant, but usually devastated when they hear they have cancer. The major reasons for suspecting that pregnancy adversely affects the clinical course of cancer is the immunologic tolerance that characterizes both conditions. It has been pointed out that normal pregnancy and cancer are the only two biologic conditions in which the antigenic tissues is tolerated by a seemingly intact system. It may be stated that the mechanisms that insure the survival of fetus during pregnancy presumably also favors the progress of the neoplasia. Management requires individualization with careful thought as whether termination is necessary or whether continuing with the pregnancy is possible prior to definitive treatment. The physician's aim must be to cure the cancer and deliver live, healthy infants. This is one question when a joint decision is probably best reached among the obstetrician, surgical and medical oncologists and other disciplines. The life-threatening cancer should be managed both for the diagnosis and treatment as in the non-pregnant state. An early small cancer gives a better prognosis than an advanced cancer. The same holds for the non-pregnant patient. The survival in the non-pregnant patient stage for stage is the same as for the pregnant patient. However, all too often in the pregnant state the cancer is more advanced than in the non-pregnant patient. The disease must be evaluated and treated in full light of its exact location in conjunction with an understanding of the natural history within the context of the pregnancy with the potentially viable unborn infant. Concern that maternal cancer may metastasize to the fetus is not justified from a review of the accumulated literature. Infrequency of fetal involvement has led to speculation about biologic protective mechanisms that may exist for the placenta and the fetus and the role circulatory separation in the placenta and immunologic responses of the fetus may play. The association of cancer in pregnancy represents a major physiologic process for the maintenance of the race and a major pathologic process that accounts for numerous deaths. It presents a controlled growth and an uncontrolled growth in the same host.

Microsatellite instability in human solid tumors.

BACKGROUND: Microsatellite instability (MIN) has been identified in a wide variety of human tumors, both familial and sporadic. In this study the authors attempted to correlate MIN with other biologic parameters to assess the significance of MIN in cancer. METHODS: The current literature up to May 1997 was reviewed critically. Comparative assessment and analysis of published MIN data in human solid tumors was addressed. RESULTS: Based on review of the current medical literature, the following conclusions can be drawn: 1) MIN associated with inherited mutations of the DNA mismatch repair genes (predominantly hMSH2/hMLH1) appears to characterize only the hereditary nonpolyposis colon carcinoma (HNPCC)/Muir-Torre family cancer syndrome category, and a subset of young colorectal carcinoma patients. Constitutional hMSH2/hMLH1 mutations rarely are reported in other than colon MIN+ tumor types; 2) MIN in non-HNPCC tumors generally is not associated with somatic mutations in the mismatch DNA repair genes most commonly involved in HNPCC; 3) loci of individual chromosomes containing microsatellite markers demonstrating high MIN frequency may be linked to particular tumor types (tumor specific MIN hot spots); 4) the gel banding patterns of MIN observed in noncolon tumors differ significantly from those reported previously in HNPCC; 5) although overall no association between MIN and histopathology is observed in the literature, a statistically higher MIN frequency has been noted in certain tumor subtypes; and 6) MIN in tumors can be associated with early or late stages of tumor progression, and also has been found in nontumor tissues. CONCLUSIONS: Molecular diagnosis using MIN analysis has been documented in at least two types of tumors (HNPCC and sporadic bladder carcinoma), suggesting a potential role of MIN in the diagnosis and/or prognosis of other solid human tumors as well.

bcl-2 and p53 in endometrial adenocarcinoma.

bcl-2 protein is expressed in normal endometrium and seems to be under hormonal control. Its role in endometrial carcinoma (EC) is largely unknown. EC can serve as a good model to investigate the role of bcl-2 in hormone-dependent neoplasia, because EC shows a spectrum of hormonally induced changes in which bcl-2 might have a potential role. p53, a tumor suppressor gene, is the most commonly mutated gene in human cancer and is a frequent abnormality in advanced EC. There is interaction between p53 and bcl-2 proteins in the regulation of physiological programmed cell death and in malignant processes. In this study, we performed immunohistochemical investigations of the expression of bcl-2 and p53 in 57 ECs, along with estrogen and progesterone receptors (ERs, PRs), to correlate the expression patterns of bcl-2 and p53 in different grades of EC with relation to clinicopathologic parameters. The average age of the patients was 61 years. Among 57 ECs, there were 13 noninvasive ECs and 44 ECs with various depths of invasion. p53 was positive in 21 of 57 cases, and bcl-2 was positive in 42 of 57. ER and PR were positive in 24 of 57 cases; PR and ER alone were positive in 15 and 2 cases, respectively. bcl-2 expression is present in ECs, and its expression is related to grade and stage. bcl-2 expression is strongly associated with PR, whereas p53 is associated with higher grade and is inversely related to PR positivity.

P53 expression in adenomyosis in endometrial carcinoma patients.

Histopathologic changes ranging from simple cystic hyperplasia to carcinoma in situ may be observed in adenomyotic foci in patients with endometrial carcinoma. These changes can be an area of concern and physicians should be aware of their clinicopathologic significance. We studied a total of 94 patients, including endometrial carcinoma with (28 patients) and without adenomyosis (56 patients), and control group of adenomyosis cases (10 patients) without endometrial carcinoma. The histopathological changes in adenomyosis in patients with endometrial carcinoma varied from endometrial glands resembling the basal endometrium (13 of 28) through simple hyperplasia (8 of 28) to complex atypical hyperplasia, resembling carcinoma in situ (7 of 28). Formalinfixed paraffin-embedded tissues from 55 patients (45 endometrial carcinomas and 10 control adenomyosis) were stained with monoclonal antibodies against P53. P53 positivity was not detected in adenomyosis cases without endometrial carcinoma but was present in 7 of the endometrial carcinoma-related cases. P53 positivity was found in 14 of 45 endometrial carcinomas studied. In all of the adenomyosis-positive cases, the endometrium was also positive. In conclusion, adenomyosis with a range of hyperplastic to atypical changes is not uncommon in adenocarcinoma patients. Our findings regarding P53 positivity in adenomyosis are consistent with the hypothesis that hyperplastic and atypical changes in adenomyosis might be due to a carcinogenic field effect in the vicinity of endometrial carcinoma rather than by direct invasion.

Prophylaxis in ovarian cancer.

The only prophylaxis for ovarian cancer is oophorectomy, except in the very rare case when an ovarian cancer appears to arise from the mesothelial tissue of the abdominal cavity. It has been shown that women who have taken the oral contraceptive pill for 4 or 5 years decreases the incidence of ovarian cancer by approximately 40%. It is estimated that the oral contraceptive pill can prevent approximately 1500 ovarian cancers each year. The postmenopausal palpable ovary syndrome is simply the palpation of what is interpreted as a normal-sized ovary in the premenopausal woman represents an ovarian tumor in the postmenopausal woman. It addresses the size and consistency and has nothing to do with the small cysts reported by the sonographer. A patient who has two first-degree blood relatives or a mother, sister, or daughter who has developed ovarian cancer premenopausally is at high risk to develop ovarian cancer. Because ovarian cancer is the leading cause of death from gynecologic cancer, it is important to explore all options for prophylaxis in the prevention of ovarian cancer.

The malpractice crisis in obstetrics and gynecology: is there a solution?

The malpractice ripoff began when the no-fault automobile accident law was passed. Many lawyers were in a panic at this time and turned to medical malpractice litigation to make a living. It became the conduit to quick wealth. The patient was the loser, the lawyer the winner, and the physician often devastated by the patient's ingratitude. For a patient-plaintiff to maintain a successful lawsuit for medical negligence against a physician, four elements must be alleged and proved in a court of law: duty, breach of duty, causation, and damages. Each must be proved by a patient to prevail against a physician. Since this is very difficult to do, the lawyers have subtly brought in a new approach called maloccurrence. This is defined as a bad outcome unrelated to the quality of care provided. The lawyers need not prove the four elements to win a malpractice case; many are won on deceit and in violation of the law by introducing the concept of maloccurrence. Not only are tort reforms needed but out of court alternatives must be mandated by law or our health care delivery system will be destroyed. Government interference and the malpractice ripoff has had a devastating effect on the talent attracted to medical school, and the number of applicants is falling rapidly. The medical malpractice crisis could soon be translated into a health delivery service crisis. Concerned citizens must join together with the medical profession and leaders of the legal profession to halt this monstrous injustice. The litigation milieu has not only paralyzed the health care industry but it has had a devastating effect across the board on the way Americans live and do business. It must be solved now for justice delayed is justice denied.

New frontiers in ovarian cancer diagnosis and management.

Ovarian carcinoma is now the leading cause of death among women. Surgery has reached its limits, and further aggressive surgery will result in an inordinate morbidity and mortality. Ovarian carcinoma is ideally treated by complete surgical removal of the cancer, followed by anti-cancer chemotherapy. Since it is often impossible to remove all of the cancer, adjunctive chemotherapy is playing an increasingly important role in the management of the cancer. New anti-cancer drugs must be found or synthesized, and new combinations of current anti-cancer drugs with mechanisms to protect the bone marrow must be explored. The field of genetics and the identification of the patient at high risk because of a familial history of ovarian cancer must be expanded. The role of tumor markers and oncogenes requires more in-depth study so that these signs can play a greater role in monitoring and identifying the patient with early ovarian cancer. The emerging fields of genetic engineering and biologic response modifiers are opening up new avenues for additional modalities of therapy. The expanding areas of research in cancer are starting to dispel the doom and gloom of the last three decades with a spirit of optimism for the diagnosis and treatment of ovarian cancer, as the new century approaches.

Contraceptives versus abortifacients.

PIP: A less-publicized aspect of the famed Louisiana abortion bill would have outlawed the use of IUDs and oral contraceptives (OCs), a provision that ignores the difference between contraceptives and abortifacients. The bill, which was vetoed by Governor Buddy Roemer, stirred widespread controversy in its effort to sharply restrict abortion. Many of those involved in the discussion -- including the State Attorney General's office -- have contended that IUDs and OCs induce abortions by destroying fertilized eggs. But such statements disregard scientific studies that indicate that both contraceptive methods work by preventing fertilization. Research has shown that IUDs, especially copper-IUDs, restrict the transport of sperm, thereby preventing fertilization. One study revealed the presence of sperm in the fallopian tubes of non-IUD users 15-30 minutes after insemination, but found no sperm in the tubes of IUD users. Inhibiting ovulation, OCs work through a combination of estrogen and progestin. OCs prevent fertility by activating various mechanisms: they suppress the release of certain hormones, and cause a thickening of the cervical mucus which impairs sperm motility. Although neither IUDs nor OCs can be considered abortifacients, a small but vocal minority has succeeded in obscuring this fact. And it is the role of science to resolve the controversy by making the facts clear.^ieng

Ovarian cancer-associated antibodies recovered from ascites: their use for the isolation of ovarian cancer-associated antigen to produce monoclonal antibodies.

Immune complexes (ICs) were recovered from the ascites of a patient with stage IV endometrioid ovarian cancer by sequential precipitation with 33% saturated ammonium sulfate and 2.5% polyethylene glycol 6000 (PEG 6000), followed by affinity chromatography on protein A-Sepharose CL-4B. The IgG-containing ICs were dissociated using 8 M urea, separated by ion-exchange chromatography on Sephadex QAE-50, and subsequently analyzed for purity by immunoelectrophoresis (IEP) and radial immunodiffusion (RID). Recovered antibody was tested for reactivity by immunohistologic techniques against paraffin-embedded tumor tissue and acetone-fixed cell suspensions of epithelial tumors. The antibody which demonstrated ovarian cancer-associated activity was absorbed with antigen extracts of breast, colon, and lung cancers as well as keratin to reduce cross-reactivity. The absorbed endometrioid ovarian cancer-associated antibody (OCAAb) was used to produce an immunoadsorbent column for the recovery of tumor-associated antigens. A mouse monoclonal antibody designated FEN-1 was produced using this antigen-containing fraction, and preliminary screening has demonstrated ovarian tumor-associated reactivity. The use of autologous ICs as reagents for preparing tumor antigen-rich immunogens may provide a valuable tool in the search for tumor-associated antigens.

Immunohistochemical characterization of a monoclonal antibody detecting an endometrioid ovarian cancer-associated antigen.

Murine monoclonal antibody FEN-1 was derived by immunizing Balb/c mice with an affinity-purified endometrioid ovarian cancer-associated antigen recovered from ascites-derived immune complexes. Splenic lymphocytes from the immunized mouse were fused with the myeloma cells SP2/0-AG14 in the presence of PEG 1500. The hybrid cultures were screened for production of immunoglobulins reactive with an extract preparation of an endometrioid ovarian tumor by enzyme-linked immunosorbent assay and flow cytometry. One of the hybrids secretes a monoclonal antibody of the IgG3 subtype designated FEN-1, which reacts with 100% of endometrioid ovarian cancer containing adenoacanthoma by indirect immunoperoxidase on paraffin-embedded tissue. No detectable levels of antigen were found in squamous metaplasia associated with nonendometrioid tumors, and no reactivity occurred against endometrial adenocarcinomas, endometriosis, or normal ovary and endometrium. The antibody does not cross-react with mucinous tumors, nonepithelial tumors of the ovary, or gastrointestinal tissue. This antibody may be used as an aid in the diagnosis of nonmucinous ovarian carcinomas by immunohistology.

Description of an endometrioid ovarian cancer cell line.

A human cell line, designated L-1, has been established from the ascites of an untreated patient with stage IV (FIGO) endometrioid ovarian cancer. This cell line initially grew uninterupted for 6 months without fibroblast contamination and contact inhibition, and has been subcultured weekly for the past 7 years. L-1 does not contain steroid hormone receptors nor does it demonstrate the presence of oncofetal antigens by immunohistochemical techniques. The doubling time of L-1 is 11.8 hr. Flow cytometric analysis reveals an aneuploid DNA peak, and an abnormal karyotype demonstrates hyperdiploidy, translocations, and deletions. Morphology, growth patterns, cytogenetic analysis, and other features of L-1 are characterized.

Present status of tumor immunology in clinical gynecology.

The function of the immune system is to protect the body from damage caused by invading microorganisms, that is, bacteria, viruses, fungi, and parasites. The humoral mechanism functions through plasma cells producing antibodies that control bacterial infections. Viruses, fungi and parasites are controlled through the thymus dependent T lymphocytes. It is now clear that cancers also invoke immunologic reactions in their hosts. Cancer cells, like bacteria and viruses have their own characteristic antigens. An antigen is defined as a substance, usually a protein or polysaccharide, that the body recognizes as foreign, and to whose presence it reacts by forming antibodies. Antigenic differences represent the first known qualitative distinction between cancer cells and their normal counterparts. These qualitative differences between normal and cancer cells had escaped other methods of investigation, but were revealed by immunological techniques that take advantage of the extraordinary power of discrimination of the immune defense mechanism itself. This mechanism is capable of distinguishing even minute differences between protein molecules, probably one different amino acid in a chain of several thousand. Burnet's clonal selection theory has become the central dogma of immunology. It can be summarized by saying that lymphocytes have been destined from time immemorial to identify a specific antigen. When the lymphocyte encounters that antigen it becomes a sensitized lymphocyte, and on contact with similar antigens again produces an immune response including the production of very potent pharmacologic agents called lymphokines. Immunodeficiency diseases are identified by increased frequency of infections in patients. The impaired immunity decreases the patient's protection against developing a malignancy. Autoimmunity is the reaction of the immune system against the body's own tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Spread and treatment of advanced ovarian cancer.

Most of the common epithelial ovarian cancers present in Stages III and IV. Although the common epithelial ovarian cancer is not truly a cancer that lends itself to surgery, it has been repeatedly reported that prognosis depends upon the amount of disease remaining at the end of the procedure. Nodules of 2 cm or greater usually mean that the patient will not be cured but may get palliation for long periods of time with adjunctive therapy. Therefore, the current philosophy is to be as aggressive as possible, surgically, without creating an inordinate morbidity and mortality. Following combination chemotherapy, if there is no evidence of disease on clinical examination--or by any laboratory or screening method--patients should be offered a second-look operation. Despite aggressive chemotherapy, approximately 50% of these patients will have residual disease at the time of the second-look procedure. In addition, 30% of the patients who have negative second-look operations will present at a later date with a recurrence of their tumour. The stage of disease at the time of the original procedure greatly influences the results, and, as would be anticipated, the results are infinitely better in those patients who have a second-look operation after Stage I cancer has been diagnosed than in patients who have a second-look procedure after an initial staging of Stage III. The best results will be achieved in those patients who have had very aggressive surgery at the initial procedure--followed by combination chemotherapy for approximately six to nine months.(ABSTRACT TRUNCATED AT 250 WORDS)