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K S McCarty

Publications and source records attributed to K S McCarty.

At least 37 records · Page 2Linked to original sources

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↗

Immunohistochemical analysis of estrogen and progesterone receptors in endometriosis: comparison with normal endometrium during the menstrual cycle and the effect of medical therapy.

Estrogen receptors (ER) and progesterone receptors (PgR) in 19 endometriotic implants from 16 normally cycling and hormonally treated women were measured using immunohistochemical techniques and compared with 34 samples of normal intrauterine endometrium. Endometriotic implants contained specific ER and PgR in both glandular epithelium and stroma. In contrast to intrauterine endometrium, receptor content among implants was noted to be more heterogeneous, and did not undergo predictable changes in response to endogenous hormones. In the endometriotic implants of patients treated with hormonal therapy, there were significant decreases in ER and PgR in both the glands and stroma relative to untreated patients. These data imply that endometriosis is unpredictable in its response to the cyclic hormonal milieu in terms of ER and PgR, but retains the ability to respond to hormonal suppression over a prolonged interval.

Adult↗

Endometrial cancer: histologic correlates of immunohistochemical localization of progesterone receptor and estrogen receptor.

Progesterone and estrogen receptor localization, using monoclonal anti-receptor antibodies JZB39 and H222, was studied in 105 endometrial adenocarcinomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining. Both anti-progesterone receptor and anti-estrogen receptor localized in the nucleus of target cells. Significant levels of progesterone receptor and estrogen receptor were seen localized in stromal and myometrial elements that diverged from the malignant epithelial component. Analyses of endometrial adenocarcinomas with anti-progesterone receptor and anti-estrogen receptor antibodies correlated with histologic differentiation. The ability to define divergent receptor populations in stromal and myometrial elements versus malignant epithelial elements indicates that immunohistochemical assay of progesterone and estrogen receptor provides information complementary to that from conventional quantitative ligand binding assays.

Adenocarcinoma↗

Reactivity of epidermal growth factor receptor monoclonal antibodies with human uterine tissues.

Two monoclonal antibodies (29.1 and 528), which were raised against the epidermal growth factor receptor, were used to evaluate expression of epidermal growth factor receptor in frozen uterine tissue with immunohistochemical techniques. Monoclonal antibody 29.1 stained only vascular endothelium and glandular epithelium in patients who were blood type A. This staining pattern is consistent with the previously reported blood type A specificity of this antibody. Monoclonal antibody 528, which recognizes a peptide determinant is thought to be specific for the epidermal growth factor receptor, stained both endometrial glands and endometrial stromal cells heavily. Faint staining was also seen in myometrium in most cases. This marked difference in expression of epidermal growth factor receptor between endometrium and myometrium contrasts with results of prior biochemical studies in which tissue homogenates were used. No variation in intensity of staining was seen between proliferative and secretory endometrium with the use of either antibody.

ABO Blood-Group System↗

Determination of sex steroid receptor in human basal cell carcinoma.

The role of estrogens in the development of skin cancer is controversial. Sex steroids have a profound effect on the epidermis and epidermal appendages. Estradiol in pharmacologic doses has been reported to stimulate basal cell carcinoma in an animal model. Sex hormones act by means of a specific protein receptor. In this study we used a specific, highly sensitive monoclonal antibody to evaluate sex steroid receptors in human basal cell carcinoma. No estrogen or progesterone receptor protein was detected in the basal cell tumor, despite clear positive control tissues. We conclude that these sex steroid receptors are not present in significant amounts to mediate a direct effect in basal carcinoma.

Adult↗

The evaluation of estrogen receptor in primary breast carcinoma by computer-assisted image analysis.

A monoclonal antibody prepared against estrogen receptor has been shown to be specific and sensitive for the detection of estrogen receptor in human breast lesions by use of immunohistochemical methods. Two hundred selected cases of primary breast carcinoma were assayed for estrogen receptor content by biochemical and immunohistochemical procedures. Quantitative evaluation was by biochemical, immunohistochemical, and automated computer-assisted image analysis using the Cell Analysis System's CAS/100 machine (Lombard, IL). Quantitative estrogen receptor content was determined by dextran-coated charcoal analysis and sucrose density gradient analysis. Immunohistochemical evaluation incorporated both intensity and distribution of staining, yielding a subjective score, histologic score (HSCORE). An objective quantitation, also incorporating intensity and distribution of staining, was done by computer-assisted image analysis, quantitative immunocytochemical score (QIC SCORE). HSCORE analysis was done with and without methyl green counterstain with no loss of sensitivity. Comparison of QIC SCORE with the biochemical and immunohistochemical analysis of the tissues examined revealed excellent sensitivities and specificities. These data suggest that automated image analysis provides an effective qualitative and quantitative means of evaluating estrogen receptor content in human breast cancers.

Antibodies, Monoclonal↗

Nonpalpable breast lesions at biopsy. A detailed analysis of radiographic features.

Several studies have demonstrated that mammographic screening of asymptomatic women results in a lower mortality rate where breast cancer is concerned. Often, screening mammograms reveal a nonpalpable radiographic abnormality and the diagnosis must be determined by an excisional biopsy after radiographic needle localization. The mammographic features associated with 179 nonpalpable breast abnormalities biopsied after radiographic needle localization were carefully characterized. There were 41 carcinomas (23%) in the series. The aim of this study was to determine which radiographic findings, if any, strongly portend the presence of either a malignant or benign lesion. Mammographic features that were commonly associated with malignancy include a change from a previous mammogram, a distortion of the surrounding architecture, the association of a soft tissue density and calcifications, and the presence of more than ten calcifications in the lesion. The radiographic abnormalities which were more commonly associated with benign disease include well-defined densities without calcifications, asymmetric densities without calcifications, and abnormalities consisting solely of a focus of mammographic calcifications that have fewer than ten concretions. The incidence of malignancy in lesions having these mammographic characteristics was only 5.5%. On the basis of these results alone, no firm threshold for biopsy can be recommended. The risks of deferring biopsy until there is worsening of the mammographic image remains to be determined.

Biopsy, Needle↗

Immunohistochemical analysis of human uterine estrogen and progesterone receptors throughout the menstrual cycle.

Estrogen receptors (ER) and progesterone receptors (PgR) were studied immunohistochemically using specific antireceptor monoclonal antibodies in uterine tissue samples from 33 women in various stages of the menstrual cycle. Immunohistochemical localization was quantified as to intensity of staining and tissue distribution in glandular epithelium, stroma, and myometrium, and the results were compared with those of standard ligand binding assays. In all samples ER and PgR localized within the nuclei of target cells. The maximal concentrations of ER and PgR occurred in the mid- to late proliferative phase of the menstrual cycle. ER content declined throughout the secretory phase. In contrast, PgR content underwent unexpectedly complex and dyssynchronous fluctuations during the secretory phase of the menstrual cycle. Specifically, the glandular epithelium had diminished PgR content, while the stroma and myometrium maintained a significant PgR content. PgR and perhaps ER are not concordant in different cell types within the uterus. Segregation of function through alteration of receptor content may be an important mechanism in steroid-dependent growth and differentiation of target tissues.

Adult↗

Lymphangiomyomatosis: a respiratory illness with an endocrinologic therapy.

Lymphangiomyomatosis should be considered when unexplained dyspnea, pneumothorax, pleural effusion or infiltrative radiographic changes occurs in a woman of childbearing age. Radiographic and pulmonary function peculiarities help in the diagnosis and evaluation of results of treatment. Diagnosis is dependent on lung biopsy and preferably identification of hormonal receptors. Endocrinological manipulation, in this study with medroxyprogesterone, decreased disability, morbidity and progression of this otherwise fatal illness. Early diagnosis and institution of treatment would appear to provide the best result.

Adult↗

A Chinese hamster ovary cell histone deacetylase that is associated with a unique class of mononucleosomes.

The chromatin-bound histone deacetylase of Chinese hamster ovary cells has been studied by using as a substrate an acetylated amino-terminal peptide of histone H4. These studies demonstrate that histone deacetylase activity is associated with mononucleosomes solubilized by digestion with micrococcal nuclease. The deacetylase activity remained bound to the nucleosomes, even in the presence of 1 M NaCl. This unique class of deacetylase-associated mononucleosomes is resolved from the major classes of mononucleosomes by polyacrylamide gel electrophoresis. These mononucleosomes contain 290 and 190 base pair DNAs and demonstrate the presence of histone H1 and non-histones HMG-1 and HMG-2 and the absence of HMG-14 and HMG-17. They are further characterized by a specific acetylation pattern of histone H4 and likely represent a functionally important chromatin-DNA complex.

Amidohydrolases↗

Sex steroid receptor distribution in the human larynx and laryngeal carcinoma.

Previous reports of estrogen receptor (ER) and progesterone receptor (PgR) in the human larynx and laryngeal carcinoma have relied on ligand-binding techniques using cytosol from tissue homogenates. These methods obscure the contribution of different tissue components to total receptor content. Recently developed, highly specific monoclonal antibodies to human ER and PgR were able to discern the presence of ER and PgR at the cellular level in 12 specimens of normal laryngeal tissue and eight laryngeal squamous cell carcinomas. Localization of ER and PgR was observed in the nuclei of vocalis muscle. No evidence of ER or PgR was found in epithelial components of the normal larynges or in laryngeal carcinomas. These results extend previous findings in lower primates and rodents to the human larynx and clarify previously reported receptor analyses of laryngeal carcinomas.

Adult↗

Estrogen receptor determination by monoclonal antibody in fine needle aspiration breast cancer cytologies: a marker of hormone response.

A monoclonal antibody (H222) prepared against purified estrogen receptor has been demonstrated to be highly specific and sensitive in an immunohistochemical assay for the detection and quantification of estrogen receptor in human breast carcinoma biopsy specimens. To evaluate the clinical applicability of this assay in cytologic specimens, response to therapy in 12 patients with recurrent breast cancer was correlated with H222 antibody localization in specimens obtained by fine needle aspiration biopsy. All 7 patients with positive H222 responded to hormone therapy (1 complete and 3 partial remissions and 3 stable disease), while 1 of 5 patients with negative H222 responded (1 stable disease). This experience suggests a role for immunohistochemical estrogen receptor determinations in prediction of response to hormonal therapy in patients whose tumor is accessible only to aspiration biopsy. Special care in the handling and interpretation of specimens is essential to optimal application of this method.

Adult↗

Breast carcinoma: an overview.

Breast cancer incidence in the United States is increasing, and the role of the gynecologist is becoming increasingly important in early detection of this common tumor of women. This article presents basic information on the anatomy and physiology of the female breast and their relationship to benign and malignant conditions commonly seen in clinical practice. An overview of detection screening, diagnosis, and treatment of breast carcinoma is also provided.

Breast↗

Endometrial adenocarcinoma estrogen receptor content: association of clinicopathologic features with immunohistochemical analysis compared with standard biochemical methods.

Endometrial adenocarcinomas from 96 patients were studied for their biochemical estrogen receptor content as well as immunohistochemical localization of estrogen receptor. A well-characterized specific monoclonal antihuman estrogen receptor antibody (H222 sp gamma) as amplified by peroxidase/antiperoxidase techniques was used for immunohistologic localization. Immunohistochemical evaluation incorporated both the intensity and distribution of staining into a semiquantitative analysis (HSCORE). The total HSCORE was the sum of the relative contributions of the four histologic components: benign epithelium, malignant epithelium, stroma, and myometrium. These results were compared with clinicopathologic features of the tumors. Excellent sensitivity (91.5%) and specificity (93.1%) were observed for immunohistochemical analyses as compared with the biochemical analysis of estrogen receptor for these tissues. The cancer component HSCORE correlated better with grade than did the biochemical estrogen receptor determination. Correlation was also observed between surgical stage and estrogen receptor content. Decreasing biochemical estrogen receptor content predicted advanced surgical stage (p = 0.0003), as did the total HSCORE (p = 0.003); however, the HSCORE of the cancer component only did not correlate with advanced surgical stage (p = 0.11). Although immunohistochemical analyses predicted biologic differentiation better than did the biochemical technique, stage correlated better with biochemical estrogen receptor analysis and total HSCORE than did the cancer component HSCORE. The HSCORE of the cancer component may better predict biologic behavior and therefore identify cancers more likely to respond to hormonal therapy.

Adenocarcinoma↗

Histologic composition of endometrial carcinomas analyzed for steroid receptor content.

One hundred endometrial carcinoma specimens were analyzed for estrogen receptor content and histologic composition. Benign tissue elements were identified in the majority of tissue sections. Histologic control of endometrial carcinoma specimens submitted for steroid receptor analysis is critical, because biochemical assays of whole tissue homogenates cannot determine receptor localization among tissue components.

Female↗

Juvenile secretory carcinoma and juvenile papillomatosis: diagnosis and treatment.

Carcinoma of the breast in the child is a rare pathologic entity, constitutes less than 1% of all breast lesions in this age group. The case of a girl with a left breast mass first noticed at 4.5 years of age is presented. An eccentric subareolar mass was excised at 6 years of age, sparing her breast bud. This biopsy contained juvenile secretory carcinoma, with additional pathologic changes characteristic of juvenile papillomatosis. Both the juvenile papillomatosis component as well as the juvenile secretory carcinoma component were devoid of estrogen and progesterone receptors in contrast to nondiseased breast tissue. The assay for these receptors was performed using a new antireceptor monoclonal antibody technique. Simple mastectomy was performed after completion excision demonstrated tumor at the pectoralis major fascia.

Antibodies, Monoclonal↗

Absence of estrogen receptor in human melanoma as evaluated by a monoclonal antiestrogen receptor antibody.

Controversy regarding the presence of estrogen receptor proteins in human melanomas persists despite extensive investigations on this subject. While apparent high-affinity binding has been observed using dextran-coated charcoal assays, several other characteristics of receptor protein have not been observed. The production of free water on incubation of tritiated estradiol (labeled in the C2 position) with melanoma cytosols suggests the possibility that the apparent binding observed is due to phenomena other than specific receptor-steroid interactions. Melanomas from 15 patients were evaluated for the presence of estrogen receptor using immunocytochemical techniques with a monoclonal antibody directed against the human estrogen receptor protein (H222 Sp gamma). Immunohistochemical evaluation included intensity and distribution of staining. None of the 15 cases demonstrated specific immunohistologic reactivity with the anti-receptor antibody. Control breast and uterine tissue confirmed the specificity and sensitivity of the methods. These results suggest that the apparent estrogen-binding capacity of human melanoma tissues is the result of interactions other than with estrogen receptor, and reaffirm the need to investigate alternate steroid protein interactions, such as catechol estrogen formation, in studying sex steroid influences on human melanoma.

Adult↗