Bcl10 is not a target for frequent mutation in human carcinomas. (1/552)

The recently described Bcl10 gene has been suggested to be a major target gene for inactivation in a variety of human cancers. In order to further evaluate the role of this gene in human adult malignancies, we have analysed a series of carcinomas for mutations in the Bcl10 gene. We have screened a panel of 174 carcinoma samples in total, comprised of 47 breast, 36 epithelial ovarian, 36 endometrial, 12 cervical, 23 colorectal and 20 head/neck carcinomas, all unselected for grade or stage. This panel reflects, in part, tumours reported to have involvement of the 1p22 region of chromosome 1, the region harbouring the Bcl10 gene. No deleterious mutations were detected in any of the samples analysed, strongly suggesting that Bcl10 is not a common target for inactivation in adult malignancies and that BCL10 is not the gene targeted for frequent inactivation at 1p22.  (+info)

Three dimensional ultrasound and power doppler in assessment of uterine and ovarian angiogenesis: a prospective study. (2/552)

AIM: To determine whether three-dimensional power Doppler can improve the recognition of pelvic tumor morphology and angiogenesis. METHODS: Using this technique we analyzed 180 adnexal masses and 110 uterine lesions. Tumor volume, morphology, and vascularity were evaluated in each patient. Irregular and randomly dispersed vessels with complex branching depicted by comprehensive three dimensional display were suggestive of pelvic malignancy, while linear-like vascular morphology, single vessel arrangement and regular branching were typical for benign structures. RESULTS: Addition of qualitative analysis of vascular architecture of adnexal tumor to morphological parameters reached 96.15% sensitivity and 98.73% specificity. When endometrial lesions were prospectively analyzed, sensitivity and specificity were 91.67% and 98.49%, respectively. Because the lowest positive predictive value of 16.67% was obtained for myometrial lesions, this method should not be advised for their eva luation. CONCLUSION: Good results achieved by three dimensional ultrasound can be explained by improved recognition of the pelvic lesion anatomy, characterization of the surface features, detection of the tumor infiltration, and precise depiction of the size and volume. Three dimensional power Doppler imaging can detect structural abnormalities of the malignant tumor vessels, such as arteriovenous shunts, microaneurysms, tumoral lakes, disproportional calibration, coiling, and dichotomous branching. Therefore it enhances and facilitates the morphologic and functional evaluation of both benign and malignant pelvic tumors.  (+info)

New approaches for estimating risk from exposure to diethylstilbestrol. (3/552)

A subgroup from a National Institute of Environmental Health Sciences, workshop concerned with characterizing the effects of endocrine disruptors on human health at environmental exposure levels considered the question, If diethylstilbestrol (DES) were introduced into the market for human use today and likely to result in low-dose exposure of the human fetus, what would be required to assess risk? On the basis of an analysis of the quality of data on human DES exposure, the critical times and doses for inducing genital tract malformations and cancer must be determined. This would be facilitated through analysis of the ontogeny of estrogen receptor expression in the developing human genital tract. Models of low-dose estrogenic effects will have to be developed for human and rodent genital tract development. Mouse models offer many advantages over other potential animal models because of the wealth of the earlier literature, the availability of sensitive end points, the availability of mutant lines, and the possibility of generating genetically engineered model systems. Through multidisciplinary approaches, it should be possible to elucidate the cellular and molecular mechanisms of endocrine disruption elicited by estrogens during development and facilitate an assessment of risk to humans.  (+info)

Gynaecological cancer. (4/552)

Gynaecological cancer encompasses a number of tumours with different epidemiology, pathology and treatment strategies. This article reviews the principal clinical advances and areas of development in cancer of the ovary, cervix, endometrium and vulva.  (+info)

Expression of folate receptor type alpha in relation to cell type, malignancy, and differentiation in ovary, uterus, and cervix. (5/552)

The folate receptor (FR) type alpha is known to be frequently overexpressed in ovarian cancer and is the target for a number of novel experimental cancer therapies. The relative levels of FR expression among specific cell types and its relationship to malignant transformation have not been adequately established because of several inherent limitations of the immunocytochemical approaches used previously. We used a quantitative in situ hybridization method to examine the expression of the mRNAs for the known isoforms of FR in paraffin-embedded tissue sections of multiple samples of the various subtypes of ovarian, uterine, and cervical cancers. Benign lesions, as well as the various normal cell types in the ovary, the uterus, and the cervix, were examined similarly. FR mRNA levels were quantitated relative to the transcript levels for beta-actin using NIH Image 1.57 computer software. The results show that the ovary, the uterus, and the cervix present different patterns of FR regulation in differentiation and in malignancy. In the ovary, benign differentiation of the germinal epithelium into mucinous or serous tumors or malignant transformation into mucinous tumors is associated with down-regulation of FR-alpha, whereas FR-alpha expression is retained in malignant lesions of serous and endometrioid differentiation. In contrast, malignant transformation of the glandular epithelial cells of the uterine endometrium is associated with de novo expression of FR-alpha. Heterogeneity in FR expression within malignant ovarian and uterine tumors is related to differentiation. In contrast to the uterus, malignant transformation of glandular epithelial cells in the cervix may frequently result in down-regulation of FR-alpha. These results shed new light for the identification of malignancies suitable for FR-mediated therapies and for prognostic/diagnostic applications of FR. They also provide a phenomenological basis for molecular studies of FR regulation in malignant cells.  (+info)

Immunohistochemical analysis of uroplakins, urothelial specific proteins, in ovarian Brenner tumors, normal tissues, and benign and neoplastic lesions of the female genital tract. (6/552)

Uroplakins are the characteristic integral membrane proteins in terminally differentiated, superficial urothelial asymmetric unit membrane. Brenner tumors of the ovary and Walthard cell nests of Fallopian tubes have been considered to represent urothelial differentiation in the female genital tract, but no definitive differentiation marker has been demonstrated supporting such a conclusion. An immunohistochemical analysis was performed to assess the expression of uroplakins in these lesions as well as in various benign and neoplastic lesions and normal tissues of the female genital tract. Focal expression of uroplakins was observed on the luminal surface of ovarian Brenner tumor cells forming microcysts in all 5 cases examined. In contrast, uroplakins were slightly expressed in only 1 of 12 cases of Walthard cell nests, even in the presence of microcyst formation. Uroplakins were not expressed in other benign or malignant lesions or normal tissues of the female genital tract. These results support the hypothesis that the Brenner tumor and possibly Walthard cell nests represent urothelial (transitional cell) differentiation.  (+info)

Application of a marker of ciliated epithelial cells to gynaecological pathology. (7/552)

BACKGROUND: The assessment of neoplastic disease in gynaecological histopathology can be complicated by the high incidence of metaplasia seen in tissues of the female genital tract. There is a need to identify specific tissue markers which can be applied in routine histopathological practice. AIM: To examine the clinical potential of a monoclonal antibody, LhS28, which reacts with basal bodies of ciliated epithelial cells. METHODS: A panel of normal and pathological gynaecological tissues was processed and labelled with LhS28. RESULTS: LhS28 immunoreactivity was found in the normal Fallopian tube where it was confined to ciliated rather than secretory epithelial cells. In the remaining specimens, LhS28 was associated exclusively with ciliated cells in tubal metaplasias of the cervix and endometrium and in benign serous lined inclusion cysts. CONCLUSIONS: LhS28 may be a valuable marker for identifying metaplasia of tubal type and may find application in distinguishing tubal metaplasia from low grade cervical glandular intraepithelial neoplasia.  (+info)

Clinical features of hypersensitivity reactions to carboplatin. (8/552)

PURPOSE: To characterize the clinical features of carboplatin-associated hypersensitivity reactions. PATIENTS: Patients with gynecologic malignancies treated at the Cleveland Clinic Foundation from June 1995 through July 1998 who experienced a carboplatin-associated hypersensitivity reaction were the subjects of this evaluation. RESULTS: Of the 205 patients treated with carboplatin during this time period, 24 (12%) developed a carboplatin hypersensitivity reaction. The median number of platinum (carboplatin plus cisplatin) courses for the first episode was eight (range, six to 21). Only three patients (13%) developed this toxicity during their initial chemotherapy regimen, with the remainder experiencing a reaction during their second (n = 15) or third (n = 6) carboplatin treatment program for recurrent disease. Thirteen patients (54%) developed at least moderately severe symptoms (diffuse erythroderma, tachycardia, chest tightness, wheezing, facial swelling, dyspnea, hypertension, or hypotension). In approximately one half of patients, the reaction developed after more than 50% of the carboplatin had been infused. Only one of three patients was successfully treated with the agent upon rechallenge. CONCLUSION: Carboplatin hypersensitivity reactions develop in patients who have been extensively pretreated with the agent. The clinical features are highly variable, but they are sufficiently different from those noted after the administration of paclitaxel that it should not be difficult to distinguish between reactions to the two agents. As carboplatin is increasingly used as initial and second-line chemotherapy of ovarian cancer and other malignancies, it can be anticipated that hypersensitivity reactions to the drug will become a more common and difficult clinical management issue.  (+info)