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Biomedical subjects

K S McCarty

Publications and source records attributed to K S McCarty.

At least 19 recordsLinked to original sources

Comparison of a novel assay for breast cancer mucin to CA15-3 and carcinoembryonic antigen.

PURPOSE: To compare the sensitivity and specificity of an automated microparticle enzyme immunoassay (MEIA) for breast cancer mucin (IMx BCM; Abbott Laboratories, North Chicago, IL) to that of CA15-3 and carcinoembryonic antigen (CEA) for detecting and monitoring breast cancer. MATERIALS AND METHODS: IMxBCM was compared to assays of CA15-3 and CEA in 630 serum specimens from healthy women, and from women with breast cancer, other malignancies, benign breast conditions, or other benign diseases. RESULTS: Analysis of the log-transforms for the three markers in all specimens showed a high correlation of IMxBCM with CA15-3 (r = .78), but not with CEA (r = .25). Based on a receiver-operating-characteristics (ROC)-curve analysis for any given specificity, IMxBCM was found to be a more sensitive marker than either CA15-3 or CEA for distinguishing 105 women with advanced or metastatic breast cancer from 89 healthy women (P = .003 and P = .04, respectively), from 98 women with benign breast conditions (P = .02 and P = .002), or from 191 women with benign diseases (P = .03 and P less than .0001). At 95% specificity, the sensitivities of IMxBCM, CA15-3, and CEA for detecting advanced or metastatic breast cancer were 69%, 51%, and 30%, respectively. Serial serum samples (n = 177) were analyzed in 20 additional metastatic breast cancer patients with measurable disease. Serial IMxBCM levels corresponded with the clinical course of disease in 80%, CA15-3 in 65%, and CEA in 60% of the 20 patients. CONCLUSIONS: Increased sensitivity of IMxBCM, despite a high correlation with CA15-3, suggests that IMxBCM and CA15-3 may recognize distinct epitopes on the same molecule. Although further research is indicated, IMxBCM may provide a promising marker in the clinical management of breast cancer patients.

Adult

Hormone-resistant endometriosis following total abdominal hysterectomy and bilateral salpingo-oophorectomy: correlation with histology and steroid receptor content.

Endometriosis is rare after hysterectomy and oophorectomy for conditions unrelated to endometriosis. We present a case of delayed development of aggressive, hormone-resistant endometriosis temporally remote from hysterectomy and oophorectomy performed for chronic pelvic inflammatory disease. Treatment with depo-medroxyprogesterone acetate resulted in continued growth of the retroperitoneal endometrioma and necessitated posterior exenteration because of the endometrioma's location. Estrogen and progesterone receptor levels were measured to clarify why this woman's endometriosis was resistant to hormone therapy. Despite administration of large amounts of depo-medroxyprogesterone acetate, the progesterone receptor content was elevated while the estrogen receptor content was undetectable. Why this patient developed this particular type of aggressive endometriosis is unclear, but the lack of down-regulation of progesterone receptors in response to high-dose progestin therapy may indicate an alteration in basic regulatory and cellular processes within the endometriotic implant.

Adult

Estrogen and progesterone receptor content of endometrial carcinomas: comparison of total tissue versus cancer component analysis.

Estrogen (ER) and progesterone (PgR) receptor values in 105 endometrial carcinomas were compared using immunocytochemical and standard biochemical techniques. Peroxidase-antiperoxidase staining for location of anti-ER (H222) and anti-PgR (JZB39) primary antibodies was used to generate a semiquantitative (HSCORE) assessment of receptor content in tissue components and the total specimen. Both total HSCORE and cancer component HSCORE correlated with log biochemical assay values for ER and PgR. Biochemical assay values, total HSCORE, and cancer component HSCORES all demonstrated internal correlations between ER and PgR levels. Correlation was somewhat closer for cancer component HSCORE values of ER and PgR than the values for total tissue HSCORE. When receptor content was analyzed by histologic grade, all three estimates of receptor status demonstrated a decreasing proportion of ER and PgR positive lesions with decreasing histologic differentiation; however, the proportion of receptor negative lesions in grade 3 lesions was much higher when using total HSCORE or cancer component HSCORE than when using biochemical assay values (P less than 0.005. Immunocytochemical techniques for localization of ER and PgR in endometrial carcinoma specimens may allow a more focused evaluation of the receptor content in the malignant elements than standard biochemical techniques.

Adenocarcinoma

Long-term prognostic implications of sex-steroid receptors in human cancer.

Progesterone receptor analysis has been used to enhance the prognostic usefulness of estrogen receptor analysis in breast cancer. Immunocytochemical assays for both steroid receptors have been shown to correlate with established biochemical techniques but lack long term clinical follow-up studies to validate their use. One hundred fifty- two patients were followed for up to 10 years after primary surgical treatment. Steroid receptor analyses, using both biochemical and immunocytochemical techniques were performed on their tumor specimens. Patients with estrogen or progesterone receptor positive tumors had longer survival than patients with negative tumors. This difference was most clearly demonstrated with immunocytochemical analysis of estrogen receptors (p = 0.04). The two methods for progesterone receptors gave very similar results. Use of multivariate analysis revealed that ER by immunocytochemical analysis was the only significant predictor of prognosis when all four variables were considered simultaneously (p = 0.04). This study suggests that immunocytochemistry gives comparable results to biochemical analysis for progesterone receptors but that immunocytochemical analysis of estrogen receptors was the stronger single prognostic indicator of the four.

Breast Neoplasms

Cystosarcoma phyllodes. Effective therapy with cisplatin and etoposide chemotherapy.

Cystosarcoma phyllodes is an unusual breast neoplasm that rarely metastasizes. Most series report chemotherapy, radiation, and hormonal therapy to be ineffective. Three patients were treated with cisplatin and etoposide combination chemotherapy with effective palliation in two patients. Radiation therapy was effective in controlling symptomatic metastasis in all three patients. Hormonal therapy was ineffective in two patients despite the presence of positive hormone receptors. Chemotherapy and radiotherapy may be more effective in the treatment of this tumor than has been reported, although there is no apparent role for hormonal therapy. Functional hormone receptors are probably not present.

Adult

Immunohistochemical expression of CA 125 in endometrial adenocarcinoma: correlation of antigen expression with metastatic potential.

Immunohistochemical localization of CA 125 using murine monoclonal antibody OC 125 was performed on fresh frozen tissue from 44 endometrial adenocarcinomas and 26 benign endometria. Immunohistochemical evaluation incorporated both intensity and distribution of staining (CA 125 HSCORE). Thirty-seven cancers (84%) and 23 benign endometria (88%) expressed immunohistochemically detectable CA 125. Staining was confined to epithelial cells and was present both on the cell membrane and in the cytoplasm. Among the 44 endometrial cancers, CA 125 HSCORE did not correlate with histological grade, depth of myometrial invasion or estrogen/progesterone receptor levels. Following surgical staging, 13 patients (30%) were found to have extrauterine metastatic disease. The median CA 125 HSCORE of patients with metastatic disease (2.25) was significantly higher than that of patients with disease confined to the uterus (0.6) (P less than 0.001). In addition, high CA 125 HSCORE also correlated with the presence of lymph node metastasis (P less than 0.001). The results of this study suggest that high CA 125 expression by endometrial adenocarcinomas is associated with increased metastatic potential.

Adenocarcinoma

Immunocytochemical analysis of estrogen receptors as a predictor of prognosis in breast cancer patients: comparison with quantitative biochemical methods.

Biochemical quantitation of estrogen receptors has been used to predict prognosis in breast cancer. Immunocytochemical analysis of estrogen receptors correlates with biochemical analysis but has very few follow-up studies in the literature to validate it as a prognostic indicator. 257 patients were followed for up to 10 years (median, 6.2 years) after primary surgical treatment. Estrogen receptor analysis using both biochemical and immunocytochemical techniques was performed on their tumor specimens. Patients with positive estrogen receptor values had longer survival than patients with negative values. This was demonstrated by both methods in the first 5 years of follow-up but only by immunochemistry after 5 years. The relationship between estrogen receptor status and disease-free interval was less strong than with survival. This study demonstrates that immunocytochemical estrogen receptor analysis was of prognostic significance.

Biomarkers, Tumor

Heterogeneity of antigen expression in benign and malignant breast and ovarian epithelial cells.

Expression of II distinct antigen families has been studied in normal and malignant epithelial cells from breast and ovary by avidin-biotin immunoperoxidase staining of frozen tissue sections. Each of the antigens was expressed in a fraction of the normal and malignant breast tissues from different individuals. Among breast and ovarian cancers, a similar fraction of tumors expressed each of the determinants. An epitope on a 42-kDa glycoprotein was expressed significantly more often by ovarian carcinomas than by benign ovarian epithelium. Several determinants on 66-, 240-kDa or high-molecular-weight proteins or glycoproteins were expressed significantly more often on benign breast epithelium than on normal ovarian epithelium. Substantial heterogeneity in antigen expression was observed among different tumor specimens. Each of 14 epithelial ovarian cancers expressed a distinctive combination of antigens. Among 18 breast cancers, 16 distinct antigenic phenotypes were observed. Interestingly, comparable heterogeneity was observed in the expression of epitopes on benign breast and ovarian epithelium, compatible with the possibility that the monoclonal reagents recognized polymorphic determinants. Substantial variations in antigen expression were also observed among cells within each neoplasm. However, when antibodies against 5 different determinants were used in combination, a majority of cells could be stained intensely in all 13 breast carcinomas tested and more than 95% of tumor cells could be stained in 10 of the 13.

Antigens, Neoplasm

Epidermal growth factor receptor expression in normal and malignant endometrium.

Epidermal growth factor receptor expression in fresh-frozen uterine tissues was studied with the use of monoclonal antibody 528, which recognizes an epitope on the external domain of the epidermal growth factor receptor. Immunohistochemically detectable epidermal growth factor receptor was seen in all uterine cell types in 19 of 20 normal uteri. Staining of endometrial glands and endometrial stromal cells was consistently greater than that of myometrium, and no variation in intensity or distribution of staining was seen during the menstrual cycle. Immunohistochemically detectable epidermal growth factor receptor was found less frequently in endometrial adenocarcinomas than in normal endometrium (p less than 0.01). Thirteen of 40 endometrial adenocarcinomas (32.5%) did not express detectable receptor. Epidermal growth factor receptor expression did not correlate with histologic grade, depth of myometrial invasion, estrogen-progesterone receptor status, the presence of extrauterine metastases, or the development of recurrent disease.

Adenocarcinoma

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